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Poon DMC, Cheung WSK, Chiu PKF, Chung DHS, Kung JBT, Lam DCM, Leung AKC, Ng ACF, O’Sullivan JM, Teoh JYC, Wu PY, Wu SKK, Kwong PWK. Treatment of metastatic castration-resistant prostate cancer: review of current evidence and synthesis of expert opinions on radioligand therapy. Front Oncol 2025; 15:1530580. [PMID: 40071082 PMCID: PMC11893367 DOI: 10.3389/fonc.2025.1530580] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/19/2024] [Accepted: 01/28/2025] [Indexed: 03/14/2025] Open
Abstract
Background Despite the boom in the development of cancer management in the last decade, most patients with metastatic prostate cancer (PCa) eventually progress to metastatic castration-resistant PCa (mCRPC) and often require multiple lines of treatment. The treatment landscape of mCRPC has evolved rapidly in recent years, introducing various types of systemic therapies, including taxane-based chemotherapy, androgen receptor pathway inhibitors, bone-targeted radionuclides (e.g., radium-223), immune checkpoint inhibitors, poly(adenosine diphosphate [ADP]-ribose) polymerase (PARP) inhibitors, and radioligand therapies (RLTs) [e.g., a prostate-specific membrane antigen (PSMA) ligand labelled with 177Lu]. Methods To help clinicians navigate the increasingly complex treatment landscape of mCRPC, this article reviews the evidence on different therapeutic regimens from pivotal trials. In addition, it reports on the results of a questionnaire developed and distributed by the Hong Kong Society of Uro-Oncology (HKSUO), with the aim of collecting the perspectives of specialists experienced in the treatment of advanced PCa in Hong Kong with regard to the clinical application of RLT, primarily [177Lu]Lu-PSMA-617/analogue therapy. Results A total of 43 questionnaire respondents (including clinical oncologists, urologists, nuclear medicine specialists, and medical oncologists) voted on 27 consensus questions divided into eight sections. Consensus or strong consensus (correspondingly ≥75% or ≥90% acceptance for an answer option) was reached for 10 questions. Subsequently, a panel of 13 local and overseas experts coordinated by the HKSUO discussed the voting results and provided further insights into certain questions. Conclusion The literature review, the voting results of the questionnaire, and the expert opinions are expected to facilitate better understanding of recent therapeutic advancements and the role of novel RLTs in the treatment of mCRPC among clinicians.
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Affiliation(s)
- Darren M. C. Poon
- Department of Clinical Oncology, State Key Laboratory of Translational Oncology, Sir YK
Pao Centre for Cancer, Hong Kong Cancer Institute, The Chinese University of Hong
Kong, Hong Kong, Hong Kong SAR, China
- Comprehensive Oncology Centre, Hong Kong Sanatorium and Hospital,
Hong Kong, Hong Kong SAR, China
| | - William S. K. Cheung
- Department of Nuclear Medicine & PET, Hong Kong Sanatorium and
Hospital, Hong Kong, Hong Kong SAR, China
| | - Peter K. F. Chiu
- S.H. Ho Urology Centre, Department of Surgery, The Chinese University of Hong
Kong, Hong Kong, Hong Kong SAR, China
| | - Daniel H. S. Chung
- Department of Clinical Oncology, Queen Elizabeth Hospital,
Hong Kong, Hong Kong SAR, China
| | - John B. T. Kung
- Nuclear Medicine Unit, Department of Diagnostic and Interventional Radiology, Queen
Elizabeth Hospital, Hong Kong, Hong Kong SAR, China
| | - Daisy C. M. Lam
- Department of Clinical Oncology, The Chinese University of Hong Kong, Prince of Wales
Hospital, Hong Kong, Hong Kong SAR, China
| | | | - Anthony C. F. Ng
- S.H. Ho Urology Centre, Department of Surgery, The Chinese University of Hong
Kong, Hong Kong, Hong Kong SAR, China
| | - Joe M. O’Sullivan
- Patrick G Johnston Centre for Cancer Research, Queen’s University, Hong Kong, Hong Kong SAR, China
| | - Jeremy Y. C. Teoh
- S.H. Ho Urology Centre, Department of Surgery, The Chinese University of Hong
Kong, Hong Kong, Hong Kong SAR, China
| | - Philip Y. Wu
- Department of Clinical Oncology, Pamela Youde Nethersole Eastern Hospital, Hong Kong, Hong Kong SAR, China
| | - Sam K. K. Wu
- Department of Nuclear Medicine & PET, Hong Kong Sanatorium and
Hospital, Hong Kong, Hong Kong SAR, China
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Zeng HA, Lv HM, Zhang MW, Niu LM, Wang J, Sun HH, Liu ZZ, Yan M. Docetaxel rechallenge in HER2-negative metastatic breast cancer: a real-world study of previously discontinued patients for non-progression reasons. J Cancer Res Clin Oncol 2025; 151:89. [PMID: 39979499 PMCID: PMC11842397 DOI: 10.1007/s00432-025-06133-w] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/26/2024] [Accepted: 02/04/2025] [Indexed: 02/22/2025]
Abstract
PURPOSE This study aimed to evaluate the efficacy and safety of docetaxel rechallenge in HER2-negative metastatic breast cancer (MBC) patients who discontinued docetaxel for reasons other than disease progression. PATIENTS AND METHODS We retrospectively analyzed HER2-negative MBC patients treated with docetaxel-based therapy (DBT) at our institution from 2010 to 2020. Objective response rate (ORR), progression-free survival (PFS), overall survival (OS), and adverse events (AEs) were assessed. Multivariate Cox regression and propensity score matching analysis (PSMA) were used to minimize bias. RESULTS Among 600 patients, 369 only received docetaxel once (control group), while 231 (38.5%) received docetaxel rechallenge as second or later-line therapy (rechallenge group). In the second-line rechallenge subset (143 patients), ORR was 51.0%, and PFS was 6.7 months. Multivariate analysis showed that a response to initial DBT (stable disease [SD] vs. complete response/partial response [CR/PR]: odds ratio [OR] 2.615, 95% confidence interval [CI] 1.373-4.981; p = 0.03) independently predicted the ORR. Beyond second-line rechallenge, the ORR and PFS were 37.5% and 5.6 months, respectively. After PSMA, the rechallenge group demonstrated significantly improved OS compared to the control group: 50.5 months vs. 46.0 months (Hazard Ratio [HR] 0.632; 95% CI 0.455-0.878; p = 0.006). The toxicities reported were manageable, primarily hematologic, with grade 3-4 events occurring in 19.5% of cases. CONCLUSION This study suggests that docetaxel rechallenge may be an effective and tolerable later-line treatment option for patients with HER2-negative MBC, particularly those who responded to initial DBT. However, further prospective, randomized controlled research is needed to fully evaluate its impact on disease response in this patient population.
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Affiliation(s)
- Hui-Ai Zeng
- Department of Breast Disease, Henan Breast Cancer Center, The Affiliated Cancer Hospital of Zhengzhou University & Henan Cancer Hospital, No.127, Dongming Road, Zhengzhou, 450008, People's Republic of China
| | - Hui-Min Lv
- Department of Breast Disease, Henan Breast Cancer Center, The Affiliated Cancer Hospital of Zhengzhou University & Henan Cancer Hospital, No.127, Dongming Road, Zhengzhou, 450008, People's Republic of China
| | - Meng-Wei Zhang
- Department of Breast Disease, Henan Breast Cancer Center, The Affiliated Cancer Hospital of Zhengzhou University & Henan Cancer Hospital, No.127, Dongming Road, Zhengzhou, 450008, People's Republic of China
| | - Li-Min Niu
- Department of Breast Disease, Henan Breast Cancer Center, The Affiliated Cancer Hospital of Zhengzhou University & Henan Cancer Hospital, No.127, Dongming Road, Zhengzhou, 450008, People's Republic of China
| | - Jing Wang
- Department of Breast Disease, Henan Breast Cancer Center, The Affiliated Cancer Hospital of Zhengzhou University & Henan Cancer Hospital, No.127, Dongming Road, Zhengzhou, 450008, People's Republic of China
| | - Hui-Hui Sun
- Department of Breast Disease, Henan Breast Cancer Center, The Affiliated Cancer Hospital of Zhengzhou University & Henan Cancer Hospital, No.127, Dongming Road, Zhengzhou, 450008, People's Republic of China
| | - Zhen-Zhen Liu
- Department of Breast Disease, Henan Breast Cancer Center, The Affiliated Cancer Hospital of Zhengzhou University & Henan Cancer Hospital, No.127, Dongming Road, Zhengzhou, 450008, People's Republic of China
| | - Min Yan
- Department of Breast Disease, Henan Breast Cancer Center, The Affiliated Cancer Hospital of Zhengzhou University & Henan Cancer Hospital, No.127, Dongming Road, Zhengzhou, 450008, People's Republic of China.
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Rosar F, Schuler J, Burgard C, Blickle A, Bartholomä M, Maus S, Petto S, Khreish F, Schaefer A, Ezziddin S. Efficacy and safety of rechallenge [ 177Lu]Lu-PSMA-617 RLT after initial partial remission in patients with mCRPC: evaluation of a prospective registry (REALITY study). Eur J Nucl Med Mol Imaging 2024; 51:4151-4162. [PMID: 39008067 PMCID: PMC11527919 DOI: 10.1007/s00259-024-06825-4] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/02/2024] [Accepted: 06/30/2024] [Indexed: 07/16/2024]
Abstract
AIM Rechallenge of [177Lu]Lu-PSMA-617 radioligand therapy (RLT) was proposed for patients who initially responded to PSMA-RLT experiencing partial remission, but relapsed into progression after a certain period of remission. However, only limited data is available regarding this approach. In this study, we analyzed the efficacy and safety profile of one or more series of [177Lu]Lu-PSMA-617 RLT rechallenge in patients from a prospective registry (REALITY Study, NCT04833517) after they initially benefited from PSMA-RLT. METHODS Forty-seven patients with metastatic castration-resistant prostate cancer (mCRPC) who had biochemical response to initial [177Lu]Lu-PSMA-617 RLT followed by disease progression received at least one (up to three) series of [177Lu]Lu-PSMA-617 RLT rechallenge. Biochemical response rates based on prostate-specific antigen (PSA) serum value, PSA-based progression-free survival (PFS) and overall survival (OS) were calculated. Adverse events of the treatment were assessed according to 'common terminology criteria for adverse events' (CTCAE). RESULTS After one series of RLT rechallenge, a PSA decline of at least 50% was achieved in 27/47 patients (57.4%). The median PFS of all patients was 8.7 mo and the median OS was 22.7 mo, each calculated from the administration of the first rechallenge series. Patients who responded (PSA decline > 50%) to the rechallenge showed a median OS of 27.3 mo. Regarding PFS, a significant correlation (r = 0.4128, p = 0.0323) was found for these patients comparing initial and rechallenge RLT. Ten patients received a second and 3 patients received a third rechallenge series with 8/10 and 3/3 patients responding to repeated RLT rechallenge. No severe deterioration of adverse events rated by CTCAE criteria was observed. CONCLUSION [177Lu]Lu-PSMA-617 RLT rechallenge is associated with significant PSA response and encouraging survival outcome as well as a very favourable safety profile and should therefore be considered as a straight-forward treatment option in mCRPC patients, who previously benefited from PSMA-RLT.
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Affiliation(s)
- Florian Rosar
- Department of Nuclear Medicine, Saarland University - Medical Center, Kirrberger Str. 100, Geb. 50, D-66421, Homburg, Germany
| | - Joelle Schuler
- Department of Nuclear Medicine, Saarland University - Medical Center, Kirrberger Str. 100, Geb. 50, D-66421, Homburg, Germany
| | - Caroline Burgard
- Department of Nuclear Medicine, Saarland University - Medical Center, Kirrberger Str. 100, Geb. 50, D-66421, Homburg, Germany
| | - Arne Blickle
- Department of Nuclear Medicine, Saarland University - Medical Center, Kirrberger Str. 100, Geb. 50, D-66421, Homburg, Germany
| | - Mark Bartholomä
- Department of Nuclear Medicine, Saarland University - Medical Center, Kirrberger Str. 100, Geb. 50, D-66421, Homburg, Germany
| | - Stephan Maus
- Department of Nuclear Medicine, Saarland University - Medical Center, Kirrberger Str. 100, Geb. 50, D-66421, Homburg, Germany
| | - Sven Petto
- Department of Nuclear Medicine, Saarland University - Medical Center, Kirrberger Str. 100, Geb. 50, D-66421, Homburg, Germany
| | - Fadi Khreish
- Department of Nuclear Medicine, Saarland University - Medical Center, Kirrberger Str. 100, Geb. 50, D-66421, Homburg, Germany
- Department of Nuclear Medicine, Campus-Fulda, University of Marburg, Fulda, Germany
| | - Andrea Schaefer
- Department of Nuclear Medicine, Saarland University - Medical Center, Kirrberger Str. 100, Geb. 50, D-66421, Homburg, Germany
| | - Samer Ezziddin
- Department of Nuclear Medicine, Saarland University - Medical Center, Kirrberger Str. 100, Geb. 50, D-66421, Homburg, Germany.
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Seifert R, Telli T, Lapa C, Desaulniers M, Hekimsoy T, Weber WA, Pfob C, Hadaschik B, Bögemann M, Schäfers M, Herrmann K, Rahbar K, Eiber M, Fendler WP. Safety and Efficacy of Extended Therapy with [ 177Lu]Lu-PSMA: A German Multicenter Study. J Nucl Med 2024; 65:909-916. [PMID: 38697669 DOI: 10.2967/jnumed.123.267321] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/22/2023] [Revised: 03/25/2024] [Indexed: 05/05/2024] Open
Abstract
Prospective results have demonstrated favorable safety and efficacy of [177Lu]Lu-PSMA radiopharmaceutical therapy for up to 6 cycles in men with metastatic castration-resistant prostate cancer. However, no systematic data are available outlining the feasibility of extended therapy beyond 6 cycles. We aim to evaluate the safety and efficacy of extended [177Lu]Lu-PSMA radiopharmaceutical therapy in patients who have received more than 6 cycles. Methods: In total, 111 patients were included in this multicenter retrospective analysis. Based on individual decisions, patients underwent uninterrupted continuation of therapy (continuous treatment) or reexposure after a therapy break (rechallenge treatment) between 2014 and 2023. Overall survival, 50% prostate-specific antigen (PSA) decline (measured 8-12 wk after treatment initiation or rechallenge), PSMA PET response, and grades per Common Terminology Criteria for Adverse Events were assessed. χ2 tests, multivariable Cox regression analysis, and log-rank tests were applied for statistical analyses. Results: Patients received extended treatment with [177Lu]Lu-PSMA, either as a continuous treatment (43/111, 38.7%) or as a rechallenge (68/111, 61.3%) treatment, with median cumulative doses of 57.4 or 60.8 GBq, respectively. Overall survival from the initiation of [177Lu]Lu-PSMA was 31.3, 23.2, and 40.2 mo for the entire cohort, the continuous treatment group, and the rechallenge treatment group, respectively. The initial 50% PSA decline was significantly higher in the retreated group than in the continuous group (57/63 [90.4%] vs. 26/42 [61.9%]; P = 0.006). A 50% PSA decline was observed in 23 of 62 patients (37.1%) after the first rechallenge. The rate of grades 3-4 toxicity was comparable between continuous and rechallenge treatments (anemia, 7/43 [16.3%] vs. 13/68 [19.1%)], P = 0.6; leukocytopenia, 1/43 [2.3%] vs. 2/67 [3.0%], P = 0.3; thrombocytopenia, 3/43 [7.0%] vs. 3/68 [4.4%], P = 0.3; renal, 2/43 [4.7%] vs. 5/68 [7.4%], P = 0.2). Conclusion: Extended therapy with [177Lu]Lu-PSMA is safe and has not been associated with increased grades 3-4 toxicity. Patient candidates for extended treatment experienced a favorable median survival of 31.3 mo from the first administration. Response under [177Lu]Lu-PSMA rechallenge demonstrated preserved efficacy of [177Lu]Lu-PSMA after a treatment break.
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Affiliation(s)
- Robert Seifert
- Department of Nuclear Medicine, University Hospital Essen, Essen, Germany
- German Cancer Consortium, University Hospital Essen, Essen, Germany
- West German Cancer, University Hospital Essen, Essen, Germany
- Department of Nuclear Medicine, University Hospital Bern, Bern, Switzerland
- Department of Nuclear Medicine, University Hospital Münster, Münster, Germany
| | - Tugce Telli
- Department of Nuclear Medicine, University Hospital Essen, Essen, Germany
- German Cancer Consortium, University Hospital Essen, Essen, Germany
- West German Cancer, University Hospital Essen, Essen, Germany
| | - Constantin Lapa
- German Cancer Consortium, University Hospital Essen, Essen, Germany
- Department of Nuclear Medicine, Faculty of Medicine, University of Augsburg, Augsburg, Germany
| | - Mélanie Desaulniers
- Department of Nuclear Medicine, University Hospital Essen, Essen, Germany
- German Cancer Consortium, University Hospital Essen, Essen, Germany
- West German Cancer, University Hospital Essen, Essen, Germany
| | - Turkay Hekimsoy
- German Cancer Consortium, University Hospital Essen, Essen, Germany
- Department of Nuclear Medicine, Klinikum Rechts der Isar, Technical University Munich, Munich, Germany
- Bavarian Cancer Research Center, Erlangen, Germany
| | - Wolfgang A Weber
- German Cancer Consortium, University Hospital Essen, Essen, Germany
- Department of Nuclear Medicine, Klinikum Rechts der Isar, Technical University Munich, Munich, Germany
- Bavarian Cancer Research Center, Erlangen, Germany
| | - Christian Pfob
- German Cancer Consortium, University Hospital Essen, Essen, Germany
- Department of Nuclear Medicine, Faculty of Medicine, University of Augsburg, Augsburg, Germany
| | - Boris Hadaschik
- German Cancer Consortium, University Hospital Essen, Essen, Germany
- West German Cancer, University Hospital Essen, Essen, Germany
- Department of Urology, University Hospital Essen, Essen, Germany; and
| | - Martin Bögemann
- West German Cancer, University Hospital Essen, Essen, Germany
- Department of Urology, University Hospital Münster, Münster, Germany
| | - Michael Schäfers
- West German Cancer, University Hospital Essen, Essen, Germany
- Department of Nuclear Medicine, University Hospital Münster, Münster, Germany
| | - Ken Herrmann
- Department of Nuclear Medicine, University Hospital Essen, Essen, Germany
- German Cancer Consortium, University Hospital Essen, Essen, Germany
- West German Cancer, University Hospital Essen, Essen, Germany
| | - Kambiz Rahbar
- West German Cancer, University Hospital Essen, Essen, Germany
- Department of Nuclear Medicine, University Hospital Münster, Münster, Germany
| | - Matthias Eiber
- German Cancer Consortium, University Hospital Essen, Essen, Germany
- Department of Nuclear Medicine, Klinikum Rechts der Isar, Technical University Munich, Munich, Germany
- Bavarian Cancer Research Center, Erlangen, Germany
| | - Wolfgang P Fendler
- Department of Nuclear Medicine, University Hospital Essen, Essen, Germany;
- German Cancer Consortium, University Hospital Essen, Essen, Germany
- West German Cancer, University Hospital Essen, Essen, Germany
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Ning W, Chang P, Zheng J, He F. The second docetaxel rechallenge for metastatic castration-resistant prostate cancer: a case report. Front Oncol 2023; 13:1185530. [PMID: 37829337 PMCID: PMC10565221 DOI: 10.3389/fonc.2023.1185530] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/13/2023] [Accepted: 09/05/2023] [Indexed: 10/14/2023] Open
Abstract
Background Docetaxel combined with prednisone plus androgen deprivation therapy (ADT) is the preferred treatment option for metastatic hormone-sensitive prostate cancer (mHSPC) or metastatic castration-resistant prostate cancer (mCRPC). With the development of next-generation hormonal agents (NHAs) and poly (ADP-ribose) polymerase (PARP) inhibitors, more aggressive first-line or later-line treatment strategies have been added to the treatment of mHSPC and mCRPC. However, docetaxel rechallenge (DR) has special clinical significance in patients with "docetaxel-sensitive" prostate cancer. There are no reports on the efficacy and safety of the second DR in mCRPC patients. Case presentation We report one patient diagnosed with mCRPC who showed progression-free survival (PFS) and overall survival (OS) benefits and safety and good lower urinary tract function after the second DR. Conclusion The second DR as a potential alternative later-line treatment strategy should be considered for patients with mCRPC who worry about the high economic burden of multigene molecular testing and PARP inhibitors as well as repeated prostate needle biopsy.
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Affiliation(s)
- Wei Ning
- Department of Urology, Second Affiliated Hospital, Army Medical University, Chongqing, China
| | - Pengkang Chang
- Department of Urology, Second Affiliated Hospital, Army Medical University, Chongqing, China
| | - Ji Zheng
- Department of Urology, Second Affiliated Hospital, Army Medical University, Chongqing, China
| | - Fan He
- Department of Urology, Second Affiliated Hospital, Army Medical University, Chongqing, China
- Urology Department, Institute of Urology (Laboratory of Reconstructive Urology), West China Hospital, Sichuan University, Chengdu, Sichuan, China
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Zhao D, Su W, Zeng L, Hu G, Tang J. Multi-protocol exploratory treatment for metastatic castration-resistant prostate cancer with BRCA mutations: a case report and literature review. Front Oncol 2023; 13:1177941. [PMID: 37234981 PMCID: PMC10206126 DOI: 10.3389/fonc.2023.1177941] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/02/2023] [Accepted: 04/28/2023] [Indexed: 05/28/2023] Open
Abstract
Most patients with metastatic hormone sensitive prostate cancer will progress to metastatic castration-resistant prostate cancer (mCRPC); Finding a highly effective, safe treatment with low recurrence rate has important clinical implications. Herein, we present a case of a 65-year-old man with castration-resistant prostate cancer treated by multi-protocol exploration. Magnetic resonance imaging (MRI) revealed prostate cancer invading the bladder, seminal vesicle glands, and peritoneum with pelvic lymph node metastasis. Transrectal B ultrasound puncture of prostate tissue was performed, and the pathological diagnosis was prostatic adenocarcinoma. CTC (Circulating tumor cell) gene test was performed in peripheral blood, and the result showed BRCA1 gene mutation. The patient died of tumor complications after trying docetaxel combined with cisplatin chemotherapy, PARP inhibitor (nilaparib), PD-1 inhibitor (tislelizumab) and other treatments. This patient showed that the selection of an individualized combination chemotherapy regimen based on genetic testing results benefited the patient's tumor control. When choosing a treatment regimen, problems such as failure to respond to re-chemotherapy and resistance to nilaparib may lead to deterioration of the condition.
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Mahler M, Al-Ezzi E, Shrem NS, Zhang L, Winquist E, Canil C, Ong M, Hansen AR, Emmenegger U. UnCHAARTED territory: The role of docetaxel rechallenge following chemohormonal therapy for metastatic castration-sensitive prostate cancer. Urol Oncol 2022; 40:539.e17-539.e22. [PMID: 36272847 DOI: 10.1016/j.urolonc.2022.09.010] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/24/2022] [Revised: 09/04/2022] [Accepted: 09/13/2022] [Indexed: 11/16/2022]
Abstract
OBJECTIVE To assess the effectiveness of docetaxel rechallenge (DR) for metastatic castration-resistant prostate cancer (mCRPC) following chemohormonal therapy for metastatic castrate-sensitive prostate cancer (mCSPC). Additionally, we sought to define clinical factors predicting treatment response. PATIENTS AND METHODS Retrospective analysis of men treated with docetaxel for mCSPC and then rechallenged in the mCRPC setting from four cancer centers in Ontario, Canada. Prostate specific antigen (PSA) response, progression-free survival (PFS), and overall survival (OS) following DR were evaluated. RESULTS Fifty five patients were identified between 2015 and 2020. Prior to DR, 94.5% of patients received androgen-receptor axis targeted therapy, 20% received radium-223, and 1.8% received cabazitaxel. Among 54 evaluable patients, 27.8% had a PSA decline ≥50%. Median PFS was 4.1 months (95% CI, 2.1-4.8) and median OS from androgen deprivation therapy initiation was 38.3 months (95% CI, 32.9-41.0). A Gleason Score of ≥8 was an independent predictor of prolonged PFS (HR 0.32, 95% CI, 0.12-0.81; P=0.02). CONCLUSIONS DR following chemohormonal therapy for mCSPC produced a meaningful PSA response in approximately one-quarter of patients, with relatively short PFS. The impact of Gleason Score on docetaxel response warrants further investigation.
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Affiliation(s)
- Mary Mahler
- Department of Medicine, University of Toronto, Toronto, Ontario, Canada; Division of Medical Oncology and Hematology, Princess Margaret Cancer Centre, Toronto, Ontario, Canada
| | - Esmail Al-Ezzi
- Division of Medical Oncology and Hematology, Princess Margaret Cancer Centre, Toronto, Ontario, Canada
| | - Noa Shani Shrem
- Department of Medicine, Division of Medical Oncology, The Ottawa Hospital Cancer Centre, Ottawa, Ontario, Canada
| | - Liying Zhang
- Division of Medical Oncology and Hematology, Odette Cancer Centre, Sunnybrook Health Sciences Centre, Toronto, Ontario, Canada
| | - Eric Winquist
- Department of Oncology, University of Western Ontario and London Health Sciences Centre, London, Ontario, Canada
| | - Christina Canil
- Department of Medicine, Division of Medical Oncology, The Ottawa Hospital Cancer Centre, Ottawa, Ontario, Canada
| | - Michael Ong
- Department of Medicine, Division of Medical Oncology, The Ottawa Hospital Cancer Centre, Ottawa, Ontario, Canada
| | - Aaron R Hansen
- Department of Medicine, University of Toronto, Toronto, Ontario, Canada; Division of Medical Oncology and Hematology, Princess Margaret Cancer Centre, Toronto, Ontario, Canada; Division of Medical Oncology, Princess Alexandra Hospital, Brisbane, Australia
| | - Urban Emmenegger
- Department of Medicine, University of Toronto, Toronto, Ontario, Canada; Division of Medical Oncology and Hematology, Princess Margaret Cancer Centre, Toronto, Ontario, Canada; Institute of Medical Science, University of Toronto, Toronto, Ontario, Canada.
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Ay S, Efiloğlu Ö, Tataroğlu Özyükseler D, Dülgar Ö, Mutlu Günaydın U, Yıldırım A, Gümüş M. Is docetaxel-free interval a predictive factor for castration-resistant prostate cancer? Actas Urol Esp 2022; 46:550-556. [PMID: 35786543 DOI: 10.1016/j.acuroe.2021.10.005] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/31/2021] [Accepted: 10/22/2021] [Indexed: 12/13/2022]
Abstract
OBJECTIVE Prostate cancer (PCa) is the second most common solid tumor in men and the fifth leading cause of cancer-related death. In advanced stage, palliative treatments are used instead of curative therapies. Therefore, finding predictive indicators seems crucial. Patients with castration-resistant prostate cancer (CRPC) that received Dx chemotherapy have been retrospectively reviewed. The aim of this study was to investigate whether docetaxel (Dx)-free interval could have a predictive value for PCa and influence other sequential therapies. MATERIAL AND METHODS This clinical trial study was performed on 104 patients at Medeniyet University Oncology Clinic in 2018-2020. All CRPC patients had metastases, received Dx as first-line treatment and underwent androgen receptor axis targeted (ARAT) therapy after disease progression. We analyzed patients' progression time after Dx therapy and the effects on sequential treatment. RESULTS After Dx therapy, all patients received ARAT (abiraterone (ABI) n: 49 (47.1%) and enzalutamide (ENZ) n: 54 (51.9%)) as a second-line treatment, except for one patient who received cabazitaxel. There was a statistically significant relationship between the Dx-free interval and duration of response to ARAT (p<0.001). The response time of ARAT treatment was <10.5 months in all patients whose Dx-free interval period was <9 months. CONCLUSIONS Our findings support the theory that Dx-free interval can be a predictive factor for CRPC. CRPC disease can be classified as Dx-sensitive disease or Dx-resistance disease, based on the Dx-free interval. Decision on subsequent treatments could be made considering this information.
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Affiliation(s)
- S Ay
- Istanbul Medeniyet University Göztepe Education and Training Hospital, Medical Oncology Clinic, Kadıköy, Istanbul, Turkey.
| | - Ö Efiloğlu
- Istanbul Medeniyet University Göztepe Education and Training Hospital, Urology Clinic, Kadıköy, Istanbul, Turkey
| | - D Tataroğlu Özyükseler
- Istanbul Kartal Lutfi Kirdar Education and Research Hospital, Medical Oncology Clinic, Kadıköy, Istanbul, Turkey
| | - Ö Dülgar
- Istanbul Medeniyet University Göztepe Education and Training Hospital, Medical Oncology Clinic, Kadıköy, Istanbul, Turkey
| | - U Mutlu Günaydın
- Istanbul Medeniyet University Göztepe Education and Training Hospital, Medical Oncology Clinic, Kadıköy, Istanbul, Turkey
| | - A Yıldırım
- Istanbul Medeniyet University Göztepe Education and Training Hospital, Urology Clinic, Kadıköy, Istanbul, Turkey
| | - M Gümüş
- Istanbul Medeniyet University Göztepe Education and Training Hospital, Medical Oncology Clinic, Kadıköy, Istanbul, Turkey
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Ay S, Efiloğlu Ö, Tataroğlu Özyükseler D, Dülgar Ö, Mutlu Günaydın U, Yıldırım A, Gümüş M. ¿Es el intervalo libre de docetaxel un factor predictivo para el cáncer de próstata resistente a la castración? Actas Urol Esp 2022. [DOI: 10.1016/j.acuro.2021.10.003] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/17/2022]
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10
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Chazan G, Anton A, Wong S, Shapiro J, Weickhardt A, Azad A, Kwan EM, Spain L, Gunjur A, Torres J, Parente P, Parnis F, Goh J, Gibbs P, Tran B. Beyond cabazitaxel: Late line treatments in metastatic castration resistant prostate cancer: A retrospective multicentre analysis. Asia Pac J Clin Oncol 2022; 18:642-649. [PMID: 35098653 DOI: 10.1111/ajco.13732] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/16/2021] [Accepted: 10/29/2021] [Indexed: 11/30/2022]
Abstract
AIMS Multiple life-prolonging therapies are available for metastatic castration-resistant prostate cancer (mCRPC). However, the optimal treatment strategy following progression through standard treatment with docetaxel, androgen receptor signaling inhibitor (ARSI) and cabazitaxel, remains unclear. We aimed to describe treatment patterns in men with mCRPC following progression on standard treatments and determine whether subsequent treatment choice impacts overall survival. METHODS Clinicopathologic and treatment data were extracted from the electronic CRPC Australian Database (ePAD) for patients who had received docetaxel, ARSIs and cabazitaxel in any order. Data were analyzed to compare groups that did versus did not receive subsequent systemic therapy. Treatment sequences, median duration of treatment, and median overall survival (mOS) were reported for each treatment group. RESULTS Ninety-eight eligible patients were identified, with 51 receiving subsequent systemic therapy. Those who received further treatment were younger (68 vs. 71 years, p < .01) but did not have any other differences in clinicopathologic features compared to those who received no further treatment. Patients who received upfront docetaxel were more likely to proceed to subsequent treatment (p = .02). Subsequent systemic therapies varied, the most common being carboplatin-based regimens (n = 13, 25.5%) and many patients were rechallenged with ARSI (n = 10, 19.6%) or docetaxel (n = 6, 11.8%). There was no difference in mOS according to subsequent systemic therapy (p = .09). CONCLUSION This retrospective multicenter analysis demonstrates the variation in treatment sequences used for mCRPC in the real-world setting. In the absence of high quality, prospective evidence, our results suggest that subsequent treatment choice does not influence survival outcomes and the optimal choice is guided by individual patient and disease-related factors.
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Affiliation(s)
- Grace Chazan
- Peter MacCallum Cancer Centre, Melbourne, Australia
| | - Angelyn Anton
- Walter and Eliza Hall Institute, Melbourne, Australia
| | | | - Julia Shapiro
- Department of Medicine, School of Clinical Sciences, Monash University, Melbourne, Australia
| | - Andrew Weickhardt
- Olivia Newton-John Cancer Wellness and Research Centre, Melbourne, Australia
| | - Arun Azad
- Peter MacCallum Cancer Centre, Melbourne, Australia.,Department of Medicine, School of Clinical Sciences, Monash University, Melbourne, Australia
| | - Edmond M Kwan
- Department of Medicine, School of Clinical Sciences, Monash University, Melbourne, Australia.,Department of Medical Oncology, Monash Health, Melbourne, Australia
| | - Lavinia Spain
- Department of Medicine, School of Clinical Sciences, Monash University, Melbourne, Australia.,Eastern Health, Melbourne, Australia
| | - Ashray Gunjur
- Olivia Newton-John Cancer Wellness and Research Centre, Melbourne, Australia
| | | | - Phillip Parente
- Department of Medicine, School of Clinical Sciences, Monash University, Melbourne, Australia.,Eastern Health, Melbourne, Australia
| | - Francis Parnis
- Adelaide Cancer Centre, Adelaide, Australia.,Department of Medicine, University of Adelaide, Adelaide, Australia
| | - Jeffrey Goh
- Royal Brisbane and Women's Hospital, Brisbane, Australia.,Department of Medicine, University of Queensland, St Lucia, Australia
| | - Peter Gibbs
- Walter and Eliza Hall Institute, Melbourne, Australia.,Western Health, Melbourne, Australia
| | - Ben Tran
- Peter MacCallum Cancer Centre, Melbourne, Australia.,Walter and Eliza Hall Institute, Melbourne, Australia
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11
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Maurice Dror C, Chi KN, Khalaf DJ. Finding the optimal treatment sequence in metastatic castration-resistant prostate cancer-a narrative review. Transl Androl Urol 2021; 10:3931-3945. [PMID: 34804836 PMCID: PMC8575566 DOI: 10.21037/tau-20-1341] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/16/2020] [Accepted: 01/29/2021] [Indexed: 11/22/2022] Open
Abstract
Over the last two decades, there has been significant progress in the treatment of metastatic prostate cancer. Multiple treatments with diverse mechanisms of action have improved clinical outcomes for patients with metastatic castration-resistant prostate cancer (mCRPC) including taxane chemotherapy, immunotherapy, potent androgen receptor pathway inhibitors (ARPI), and radiopharmaceuticals (radium-223). As these treatments have entered standard clinical practise, clinicians have been challenged on how to optimally select and sequence them as the landmark studies establishing their efficacy had control arms with placebo or minimally effective therapy and there is a paucity of prospective trials examining treatment sequencing. More recently, the situation has been further complicated as the earlier up-front use of docetaxel and ARPI with standard gonadal testosterone inhibition has been shown to impart substantial improvements in disease control and survival for patients with castration sensitive prostate cancer. As new therapies enter into clinical practise such as the inhibitors of Poly (ADP-Ribose) Polymerase and Prostate Specific Membrane Antigen (PSMA)-targeted therapy, how to optimally select and sequence available treatments will be a continued dilemma in the absence of validated predictive biomarkers. This review will summarize the literature supporting the use of each active agent in mCRPC. We will propose a framework which will guide the selection of appropriate agents based on prior therapies, disease characteristics and biomarkers.
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Affiliation(s)
| | - Kim N Chi
- BC Cancer Vancouver, Vancouver, British Columbia, Canada.,Vancouver Prostate Centre, Department of Urologic Sciences, University of British Columbia, Vancouver, British Columbia, Canada
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12
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Pobel C, Auclin E, Teyssonneau D, Laguerre B, Cancel M, Boughalem E, Noel J, Brachet PE, Maillet D, Barthelemy P, Helissey C, Thibault C, Oudard S. Cabazitaxel multiple rechallenges in metastatic castration-resistant prostate cancer. Cancer Med 2021; 10:6304-6309. [PMID: 34382352 PMCID: PMC8446560 DOI: 10.1002/cam4.4172] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/23/2021] [Revised: 07/05/2021] [Accepted: 07/07/2021] [Indexed: 01/22/2023] Open
Abstract
Introduction Cabazitaxel multiple rechallenges may be a treatment option in heavily pretreated patients with metastatic castration‐resistant prostate cancer (mCRPC) who had a good initial response to cabazitaxel and who are still fit to receive it. Our objective was to assess the efficacy and toxicity of multiple rechallenges. Patients and methods We retrospectively identified 22 mCRPC patients previously treated with docetaxel and/or androgen receptor‐targeted agents who received multiple cabazitaxel rechallenges in 9 French centers. Cabazitaxel was initiated at a dose of 25 mg/m2 q3week. A reduced dose (20 mg/m2 q3w) or an alternative schedule (mainly 16 mg/m2 q2w) was increasingly used for subsequent rechallenges. Progression‐free survival, prostate‐specific antigen (PSA) response, best clinical response, and grade ≥3 toxicities were collected. Overall survival was calculated from various time points. Results Twenty‐two patients with an initial response to cabazitaxel were rechallenged at least twice. The median number of cabazitaxel cycles was 7 at first cabazitaxel treatment, 6 at first rechallenge, and 5 at subsequent rechallenges. Median progression‐free survival at first rechallenge was 9.6 months and 5.6 months at second rechallenge. Median overall survival was 50.9 months from the first cabazitaxel dose, 114.9 months from first life‐extending therapy initiation in mCRPC, and 105 months from mCRPC diagnosis. There was no cumulative grade ≥3 neuropathy or nail disorder and one case of febrile neutropenia. Conclusion Cabazitaxel multiple rechallenges may be a treatment option without cumulative toxicity in heavily pretreated patients having a good response to first cabazitaxel use and still fit to receive it. Novelty & Impact Statements Patients with metastatic castration‐resistant prostate cancer can be treated with Cabazitaxel after docetaxel and androgen receptor‐targeted agent. This chemotherapy can be used multiple times with efficacy and manageable toxicity.
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Affiliation(s)
- Cedric Pobel
- Oncology Department, Hôpital Européen Georges Pompidou, AP-HP, University of Paris, Paris, France
| | - Edouard Auclin
- Oncology Department, Hôpital Européen Georges Pompidou, AP-HP, University of Paris, Paris, France
| | | | | | | | - Elouen Boughalem
- Oncology Department, Institut de Cancérologie de l'Ouest, Angers, France
| | - Johanna Noel
- Oncology Department, Hôpital Européen Georges Pompidou, AP-HP, University of Paris, Paris, France
| | | | - Denis Maillet
- Oncology Department, University hospital of Lyon, France
| | - Philippe Barthelemy
- Medical Oncology, University Hospital Strasbourg / Institut de Cancérologie Strasbourg Europe, Strasbourg, France
| | - Carole Helissey
- Clinical Research Unit, Military Hospital Begin, Saint Mandé, France
| | - Constance Thibault
- Oncology Department, Hôpital Européen Georges Pompidou, AP-HP, University of Paris, Paris, France
| | - Stéphane Oudard
- Oncology Department, Hôpital Européen Georges Pompidou, AP-HP, University of Paris, Paris, France
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13
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Maj-Hes A, Szarvas T, Sevcenco S, Kramer G. Multiple Docetaxel Retreatments Without Prednisone for Metastatic Castration-Resistant Prostate Cancer in the Docetaxel-Only Era: Effects on PSA Kinetics and Survival. Adv Ther 2021; 38:3831-3841. [PMID: 34043207 PMCID: PMC8280015 DOI: 10.1007/s12325-021-01778-8] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/07/2021] [Accepted: 05/06/2021] [Indexed: 01/10/2023]
Abstract
Introduction This study aimed to assess the effects of multiple docetaxel (DOC) treatments on prostate-specific antigen (PSA) kinetics and survival among patients with metastatic castration-resistant prostate cancer (mCRPC) who were sensitive to first-line DOC and received no other life-prolonging agents. To eliminate the effect of cortisone on serum PSA, only patients who were treated without prednisone were included. Methods This IRB-approved retrospective study evaluated 52 patients with mCRPC who were retreated using DOC after first-line DOC (without prednisone in both cases), based on a PSA response of > 50% and no radiographic progression. Twenty-three PSA-based factors, including static and kinetic PSA measures, were evaluate for their ability to predict overall survival (OS) Results The patients received 688 cycles of DOC in 143 series, including 91 courses of retreatments (1 cycle: 28 patients, 2 cycles: 14 patients, 3 cycles: 8 patients, 4 cycles: 1 patient, and 7 cycles: 1 patient). The median overall number of cycles per patient was 12 (range: 7–31). The median durations of the first, second, and third holidays were 18 weeks (6–60 weeks), 16 weeks (3–44 weeks), and 17 weeks (8–51 weeks), respectively. The median OSs were 22 months (10.5–70 months) after the first DOC treatment and 14 months (3–65 months) after the second DOC treatment. The > 50% PSA decline rate was 48% after retreatment. Short treatment holidays (< 3 months) were associated with shortened OS (p = 0.01). In the multivariate analysis, a 25% PSA increase over the nadir was the strongest predictor of survival (HR: 3.20, 95% CI: 1.47–6.99, p = 0.003). Conclusions DOC retreatment without prednisone had anti-tumor activity in a considerable proportion of mCRPC cases that were initially sensitive to first-line DOC. A 25% PSA increase over the nadir might predict acquired DOC resistance.
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14
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Westaby D, Viscuse PV, Ravilla R, de la Maza MDLDF, Hahn A, Sharp A, de Bono J, Aparicio A, Fleming MT. Beyond the Androgen Receptor: The Sequence, the Mutants, and New Avengers in the Treatment of Castrate-Resistant Metastatic Prostate Cancer. Am Soc Clin Oncol Educ Book 2021; 41:e190-e202. [PMID: 34061561 DOI: 10.1200/edbk_321209] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/17/2022]
Abstract
Targeting the androgen receptor by depriving testosterone with gonadotropin-releasing hormone agonists or antagonists, or surgical castration, has been the backbone of metastatic prostate cancer treatment. Although most prostate cancers initially respond to androgen deprivation, metastatic castration-resistant prostate cancer evolves into a heterogeneous disease with diverse drivers of progression and mechanisms of therapeutic resistance. Development of castrate resistance phenotype is associated with lethality despite the recent noteworthy strides gained via increase in therapeutic options. Identification of novel therapeutics to further improve survival and achieve durable responses in metastatic castration-resistant prostate cancer is a clinical necessity. In this review, we outline the existing avengers for treatment of metastatic castration-resistant prostate cancer by clinical presentation, placing into context the clinical state of the patient, such as burden of disease and symptoms. Doing so might aid in the ability to optimize the sequence of agents and allow for maximal exposure to life-prolonging therapeutics. Realizing the limitations of the androgen signaling inhibition, we explore the androgen-indifferent prostate cancer: the mutants. Classically, these subtypes have been associated with variant histology, but androgen-indifferent prostate cancer features are now frequently observed in association with heterogeneous morphologies, including double-negative prostate cancers, lacking both androgen receptor and neuroendocrine features, or clinicopathologic criteria, such as the aggressive variant prostate cancer criteria. The framework of new avengers against metastatic castration-resistant prostate cancer based on mechanism, including DNA repair, immune checkpoint inhibition, PTEN/PI3K/AKT pathway, prostate-specific membrane antigen targets, bispecific T-cell engagers, and radionuclide therapies, is summarized in this review.
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Affiliation(s)
- Daniel Westaby
- The Institute of Cancer Research and The Royal Marsden Hospital, London, United Kingdom
| | - Paul V Viscuse
- Division of Cancer Medicine, University of Texas MD Anderson Cancer Center, Houston, TX
| | - Rahul Ravilla
- US Oncology Research, New York Oncology Hematology, Albany, NY
| | | | - Andrew Hahn
- Division of Cancer Medicine, University of Texas MD Anderson Cancer Center, Houston, TX
| | - Adam Sharp
- The Institute of Cancer Research and The Royal Marsden Hospital, London, United Kingdom
| | - Johann de Bono
- The Institute of Cancer Research and The Royal Marsden Hospital, London, United Kingdom
| | - Ana Aparicio
- Department of Genitourinary Medical Oncology, University of Texas MD Anderson Cancer Center, Houston, TX
| | - Mark T Fleming
- US Oncology Research, Virginia Oncology Associates, Norfolk, VA
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15
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Yang X, Jiang D, Li Y, Zhang T, Xu D, Chen X, Pang J. Which Way to Choose for the Treatment of Metastatic Prostate Cancer: A Case Report and Literature Review. Front Oncol 2021; 11:659442. [PMID: 33981608 PMCID: PMC8107685 DOI: 10.3389/fonc.2021.659442] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/27/2021] [Accepted: 03/31/2021] [Indexed: 12/24/2022] Open
Abstract
Background Prostate cancer (PCa) is the second most common cancer among males in the world and the majority of patients will eventually progress to the metastatic phase. How to choose an effective way for the treatment of metastatic PCa, especially in the later stage of the disease is still confusing. Herein we reported the case of a patient diagnosed with metastatic PCa and conducted a literature review on this issue. Case Presentation A 57-year-old man with metastatic PCa had been managed by Dr. J.P. since April 2012 when the patient was admitted to the Third Affiliated Hospital of Sun Yat-sen University by aggravating frequent urination and dysuria. The prostate-specific antigen (PSA) concentration was 140 ng/ml, and the diagnosis of PCa was confirmed by prostate biopsy, with Gleason score 4 + 5 = 9. Chest CT and bone scan indicated multiple metastases in the lungs and bones. Triptorelin, bicalutamide, zoledronic acid, and docetaxel were then administered, six cycles later, the metastatic tumors in the lungs disappeared and those in the bones lessened significantly, along with a remarkable reduction in PSA level (< 2 ng/ml). Intermittent androgen deprivation was subsequently conducted until August 2018, when the serum PSA level was found to be 250 ng/ml, again docetaxel 75 mg/m2 was administered immediately but the patient was intolerant this time. Instead, abiraterone was administered until March 2019 because of intolerable gastrointestinal side-effects and increasing PSA level. In October 2019, the patient came to our center, a modified approach of docetaxel (day 1 40 mg/m2 + day 8 35 mg/m2) was administered. Luckily, the PSA level decreased rapidly, the bone pain was greatly relieved, and no obvious side effects occurred. However, four cycles later, docetaxel failed to work anymore, the metastatic tumor in the liver progressed. We proposed several regimens as alternatives, but they were soon denied due to the high prices or unavailability or uncertain effect of the drugs. In addition, the patient’s condition deteriorated speedily and can no longer bear any aggressive treatment. Finally, the patient died of multiple organ failure in August 2020. Conclusion The experiences of this case provide valuable evidence and reference for the treatment choices of metastatic PCa, in some circumstances modified and advanced regimens may produce unexpected effects.
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Affiliation(s)
- Xiangwei Yang
- Department of Urology, Kidney and Urology Center, Pelvic Floor Disorders Center, The Seventh Affiliated Hospital, Sun Yat-Sen University, Shenzhen, China
| | - Donggen Jiang
- Department of Urology, Kidney and Urology Center, Pelvic Floor Disorders Center, The Seventh Affiliated Hospital, Sun Yat-Sen University, Shenzhen, China
| | - Yamei Li
- Department of Urology, Kidney and Urology Center, Pelvic Floor Disorders Center, The Seventh Affiliated Hospital, Sun Yat-Sen University, Shenzhen, China
| | - Tianzhi Zhang
- Department of Pathology, The Seventh Affiliated Hospital, Sun Yat-Sen University, Shenzhen, China
| | - Duanya Xu
- Department of Urology, Kidney and Urology Center, Pelvic Floor Disorders Center, The Seventh Affiliated Hospital, Sun Yat-Sen University, Shenzhen, China
| | - Xianju Chen
- Department of Urology, Kidney and Urology Center, Pelvic Floor Disorders Center, The Seventh Affiliated Hospital, Sun Yat-Sen University, Shenzhen, China
| | - Jun Pang
- Department of Urology, Kidney and Urology Center, Pelvic Floor Disorders Center, The Seventh Affiliated Hospital, Sun Yat-Sen University, Shenzhen, China
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16
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Cao JZ, Pan JF, Ng DM, Ying MQ, Jiang JH, Ma Q. Maintenance Long-Term Multiple Cycles Treatment with Docetaxel in Metastatic Castration-Resistant Prostate Cancer: A Report of Three Cases. Onco Targets Ther 2021; 14:2797-2803. [PMID: 33907422 PMCID: PMC8071213 DOI: 10.2147/ott.s297603] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/15/2020] [Accepted: 03/10/2021] [Indexed: 11/29/2022] Open
Abstract
Prostate cancer (PCa) is one of the most common types of malignancy, most patients with PCa will eventually progress to metastatic castration-resistant prostate cancer (mCRPC), which has a poor prognosis. Since 2004, chemotherapy has been approved by the FDA as the first-line treatment for mCRPC, and docetaxel-based regimens have been shown to improve both the patients’ symptoms and overall survival (OS). 10 cycles of docetaxel therapy are usually given to patients with mCPRC, but there is still no consensus on the optimal number of treatment cycles. Here, we present three cases of mCRPC patients that received maintenance long-term multiple-cycles docetaxel treatment. We believe that this new treatment strategy may benefit carefully selected mCRPC patients and provide several key advantages such as maximum exposure to drugs, improvements in drug efficacy, and reduce the risk of developing drug resistance.
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Affiliation(s)
- Jian-Zhou Cao
- Medical School, Ningbo University, Ningbo, Zhejiang, 315211, People's Republic of China.,Comprehensive Urogenital Cancer Center, Ningbo First Hospital, The Affiliated Hospital of Ningbo University, Ningbo, Zhejiang, 315010, People's Republic of China
| | - Jin-Feng Pan
- Medical School, Ningbo University, Ningbo, Zhejiang, 315211, People's Republic of China.,Comprehensive Urogenital Cancer Center, Ningbo First Hospital, The Affiliated Hospital of Ningbo University, Ningbo, Zhejiang, 315010, People's Republic of China
| | - Derry Mingyao Ng
- Medical School, Ningbo University, Ningbo, Zhejiang, 315211, People's Republic of China.,Translational Research Laboratory for Urology, The Key Laboratory of Ningbo City, Ningbo First Hospital, The Affiliated Hospital of Ningbo University, Ningbo, Zhejiang, 315010, People's Republic of China
| | - Meng-Qi Ying
- Medical School, Ningbo University, Ningbo, Zhejiang, 315211, People's Republic of China
| | - Jun-Hui Jiang
- Department of Urology, Ningbo First Hospital, The Affiliated Hospital of Ningbo University, Ningbo, Zhejiang, 315010, People's Republic of China.,Ningbo Clinical Research Center for Urological Disease, Ningbo, Zhejiang, 315010, People's Republic of China
| | - Qi Ma
- Comprehensive Urogenital Cancer Center, Ningbo First Hospital, The Affiliated Hospital of Ningbo University, Ningbo, Zhejiang, 315010, People's Republic of China.,Translational Research Laboratory for Urology, The Key Laboratory of Ningbo City, Ningbo First Hospital, The Affiliated Hospital of Ningbo University, Ningbo, Zhejiang, 315010, People's Republic of China.,Department of Urology, Ningbo First Hospital, The Affiliated Hospital of Ningbo University, Ningbo, Zhejiang, 315010, People's Republic of China.,Ningbo Clinical Research Center for Urological Disease, Ningbo, Zhejiang, 315010, People's Republic of China
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17
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Leung DKW, Chiu PKF, Ng CF, Teoh JYC. Novel Strategies for Treating Castration-Resistant Prostate Cancer. Biomedicines 2021; 9:biomedicines9040339. [PMID: 33801751 PMCID: PMC8066514 DOI: 10.3390/biomedicines9040339] [Citation(s) in RCA: 15] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/13/2021] [Revised: 03/23/2021] [Accepted: 03/23/2021] [Indexed: 01/06/2023] Open
Abstract
The development of castration resistance is an inevitable pathway for the vast majority of patients with advanced prostate cancer. Recently, there have been significant breakthroughs in the understanding and management options of castration-resistant prostate cancer. Three novel hormonal agents showed survival benefits in non-metastatic patients. As for metastatic disease, there was an even wider range of management options being investigated. This review summarized advances in the management of castration-resistant prostate cancer (CRPC) including emerging data on novel imaging techniques and treatment strategies.
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18
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de Velasco G, Ruiz-Granados Á, Reig O, Massari F, Climent Duran MA, Verzoni E, Graham J, Llarena R, De Tursi M, Donskov F, Iglesias C, Pandha HS, Garcia Del Muro X, Procopio G, Oudard S, Castellano D, Albiges L. Outcomes of systemic targeted therapy in recurrent renal cell carcinoma treated with adjuvant sunitinib. BJU Int 2021; 128:254-261. [PMID: 33547860 DOI: 10.1111/bju.15356] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/29/2022]
Abstract
OBJECTIVE To assess the efficacy and tolerability of rechallenge with sunitinib and other targeted therapies (TTs) in patitents with relapsed recurrent renal cell carcinoma (RCC) in the advanced setting. METHODS In this multi-institutional retrospective study, patients with relapsed RCC were rechallenged with sunitinib or other systemic TTs as a first-line therapeutic approach after failed adjuvant sunitinib treatment. Patient characteristics, treatments and clinical outcomes were recorded. The primary endpoint was progression-free survival (PFS). Secondary endpoints were objective response rate (ORR) and overall survival (OS). RESULTS A total of 34 patients with relapses were recorded, and 25 of these (73.5%) were men. Twenty-five patients were treated with systemic TT: 65% of patients received TT against the vascular endothelial growth factor pathway (including sunitinib), 21.7% received mammalian target of rapamycin inhibitors and 13% received immunotherapy. The median (interquartile range) time to relapse was 20.3 (5.2-20.4) months from diagnosis, and 7.5 months (1.0-8.5) from the end of adjuvant suntinib treatment. At a median follow-up of 23.5 months, 24 of the 25 patients had progressed on first-line systemic therapy. The median PFS was 12.0 months (95% confidence interval [CI] 5.78-18.2). There were no statistical differences in PFS between different treatments or sunitinib rechallenge. PFS was not statistically different in patients relapsing on or after adjuvant suntinib treatment (≤ 6 or >6 months after adjuvant suntinib ending). The ORR was 20.5%. The median OS was 29.1 months (95% CI 16.4-41.8). CONCLUSIONS Rechallenge with sunitinib or other systemic therapies is still a feasible therapeutic option that provides patients with advanced or metastastic RCC with additional clinical benefits with regard to PFS and OS after failed response to adjuvant sunitinib.
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Affiliation(s)
- Guillermo de Velasco
- Medical Oncology Department, Hospital Universitario 12 de Octubre, Madrid, Spain
| | - Álvaro Ruiz-Granados
- Medical Oncology Department, Hospital Universitario 12 de Octubre, Madrid, Spain
| | - Oscar Reig
- Translational Genomics and Targeted Therapeutics in Solid Tumours Lab, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain
| | - Francesco Massari
- Oncologia Medica, Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italia.,Division of Oncology, S. Orsola-Malpighi Hospital, Bologna, Italy
| | | | - Elena Verzoni
- Medical Oncology Department, Fondazione IRCCS Istituto Nazionale dei Tumori di Milano, Milan, Italy
| | | | | | - Michele De Tursi
- Department of Oncology and Neurosciences, Consorzio Interuniversitario Nazionale per la Bio-Oncologia, University G. d'Annunzio, Chieti, Italy
| | - Frede Donskov
- Department of Oncology, Aarhus University Hospital, Aarhus, Denmark
| | - Clara Iglesias
- Hospital Universitario Central de Asturias, Oviedo, Spain
| | | | - Xavier Garcia Del Muro
- Department of Medical Oncology, Institut Català d'Oncologia L'Hospitalet, Hospital Duran i Reynals, L'Hospitalet de Llobregat, Barcelona, Spain
| | - Giuseppe Procopio
- Medical Oncology Department, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy
| | - Stephane Oudard
- Medical Oncology Department, Georges Pompidou Hospital, University of Paris, Paris, France
| | - Daniel Castellano
- Medical Oncology Department, Hospital Universitario 12 de Octubre, Madrid, Spain
| | - Laurence Albiges
- Medical Oncology, Gustave Roussy, Université Paris-Saclay, Villejuif, France
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19
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Assi T, Rassy E, Farhat F, Kattan C, Kattan J. Docetaxel Rechallenge in Patients with Metastatic Prostate Cancer: A Comprehensive Review. Oncol Res Treat 2020; 43:299-306. [PMID: 32380503 DOI: 10.1159/000506693] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/03/2019] [Accepted: 02/19/2020] [Indexed: 11/19/2022]
Abstract
BACKGROUND Recent years have witnessed a huge shift in the management and prognosis of metastatic prostate cancer with the advent of new-generation anti-hormonal treatments. Docetaxel, which was initially approved in the castrate-resistant prostate cancer setting, has been approved in the earlier course of the disease as it is still castrate sensitive. SUMMARY Apart from cabazitaxel and in the absence of other effective chemotherapies, docetaxel rechallenge (DR) in patients with proved sensitivity to docetaxel in the earlier stage of the disease remains a possible option. Unfortunately, the pivotal trials rarely reported on the outcomes of docetaxel retreatment which seems a plausible option in patients initially responding to docetaxel and maintaining a minimum progression-free interval of 3-6 months. In this review, a summary of the clinical evidence and potential concerns for the use of DR in patients with metastatic prostate cancer will be presented. Key Messages: Pivotal trials of docetaxel in metastatic castrate-sensitive prostate cancer as well as metastatic castrate-resistant prostate cancer have not reported on the outcomes of DR except in the GETUG-AFU 15 trial where the outcomes were disappointing. Based on the published retrospective data, DR may be effective in patients who initially responded to docetaxel and maintained a progression-free interval exceeding 6 months.
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Affiliation(s)
- Tarek Assi
- Department of Oncology, Faculty of Medicine, Saint Joseph University, Beirut, Lebanon, .,Oncology Department, Hammoud Hospital UMC, Saida, Lebanon,
| | - Elie Rassy
- Department of Oncology, Faculty of Medicine, Saint Joseph University, Beirut, Lebanon
| | - Fadi Farhat
- Department of Oncology, Faculty of Medicine, Saint Joseph University, Beirut, Lebanon.,Oncology Department, Hammoud Hospital UMC, Saida, Lebanon
| | - Clarisse Kattan
- Department of Oncology, Faculty of Medicine, Saint Joseph University, Beirut, Lebanon
| | - Joseph Kattan
- Department of Oncology, Faculty of Medicine, Saint Joseph University, Beirut, Lebanon
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20
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Caffo O, Wissing M, Bianchini D, Bergman A, Thomsen FB, Schmid S, Yu EY, Bournakis E, Sella A, Zagonel V, De Giorgi U, Tucci M, Gelderblom H, Galli L, Pappagallo G, Bria E, Sperduti I, Oudard S. Survival Outcomes From a Cumulative Analysis of Worldwide Observational Studies on Sequential Use of New Agents in Metastatic Castration-Resistant Prostate Cancer. Clin Genitourin Cancer 2019; 18:69-76.e4. [PMID: 31767448 DOI: 10.1016/j.clgc.2019.09.010] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/19/2019] [Revised: 08/12/2019] [Accepted: 09/10/2019] [Indexed: 12/15/2022]
Abstract
INTRODUCTION The sequential use of a number of new agents (NAs) have improved the overall survival (OS) of patients with metastatic castration-resistant prostate cancer whose disease progresses after docetaxel (DOC) treatment. The aim of this study was to assess the cumulative survival outcomes of different sequencing strategies by evaluating the individual data from published studies of patients treated with a post-DOC treatment sequence of 2 NAs. PATIENTS AND METHODS The patients' individual data were analyzed to investigate whether different sequencing strategies lead to differences in OS. RESULTS We analyzed the data of 1099 evaluable patients. Among the patients treated with a second-line new hormone agent (NHA), median OS from the start of third-line treatment was significantly longer in the patients treated with cabazitaxel (CABA) than in those treated with abiraterone acetate or enzalutamide. Median cumulative OS (cumOS) from the start of second-line treatment was 21.1 months in the patients who received NHA then NHA, 22.1 months in those who received NHA then CABA, and 21.0 months in those who received CABA then NHA. Among the patients with a second-line progression-free survival of ≥6 months, median cumOS was significantly longer in patients who received CABA-including sequences than in those treated with NHA then NHA sequences (29.5 vs. 24.8 months; P = .03). CONCLUSION Our findings suggest that the sequential use of NAs with different mechanisms of action improves cumOS regardless of the order in which they are administered, thus supporting the hypothesis of cross-resistance between the 2 NHAs.
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Affiliation(s)
- Orazio Caffo
- Medical Oncology Department, Santa Chiara Hospital, Trento, Italy.
| | - Michel Wissing
- Medical Oncology Department, University Medical Centre, Leiden, the Netherlands
| | - Diletta Bianchini
- Division of Clinical Studies, Prostate Cancer Targeted Therapies Group, Royal Marsden NHS Foundation Trust, Sutton, United Kingdom
| | - Andries Bergman
- Division of Internal Medicine (MOD) and Oncogenomics, Netherlands Cancer Institute, Amsterdam, the Netherlands
| | | | - Sebastian Schmid
- Klinik und Poliklinik für Urologie, Klinikum rechts der Isar der Technischen Universität München, München, Germany
| | - Evan Y Yu
- Department of Medicine, University of Washington School of Medicine, Seattle, WA
| | - Evangelos Bournakis
- Oncology Department, ARETAIEIO University Hospital of Athens, IASO General Clinic of Athens, Athens, Greece
| | - Avishay Sella
- Department of Oncology, Yitzhak Shamir Medical Center, Assaf Harofe Campus Harofeh Medical Center, Sackler School of Medicine, Tel-Aviv, Israel
| | - Vittorina Zagonel
- Medical Oncology Department, Istituto Oncologico Veneto, Padua, Italy
| | - Ugo De Giorgi
- Medical Oncology Department, Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori, Meldola, Italy
| | - Marcello Tucci
- Medical Oncology Department, Azienda Ospedaliera Universitaria S. Luigi Gonzaga, Orbassano, Italy
| | - Hans Gelderblom
- Medical Oncology Department, University Medical Centre, Leiden, the Netherlands
| | - Luca Galli
- Medical Oncology Department, Azienda Ospedaliera Universitaria, Pisa, Italy
| | | | - Emilio Bria
- Oncology Unit, Università Cattolica del Sacro Cuore, Fondazione Policlinico "A. Gemelli", Rome, Italy
| | - Isabella Sperduti
- Biostatistical Unit, Regina Elena National Cancer Institute, Rome, Italy
| | - Stephane Oudard
- Service de cancérologie médicale, Hôpital Européen Georges Pompidou, René Descartes University, Paris, France
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21
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Caffo O, Maines F, Kinspergher S, Veccia A, Messina C. Sequencing strategies in the new treatment landscape of prostate cancer. Future Oncol 2019; 15:2967-2982. [PMID: 31424285 DOI: 10.2217/fon-2019-0190] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/11/2022] Open
Abstract
Over the last 10 years, a number of new agents approved for the treatment of metastatic castration-resistant prostate cancer have led to a significant improvement in overall survival. The addition of new agents to androgen deprivation therapy has also allowed a paradigmatic change in the treatment of metastatic hormone-sensitive prostate cancer by improving overall survival in comparison with androgen deprivation therapy alone. Furthermore, recent data concerning the efficacy of three different androgen receptor-targeting agents in patients with nonmetastatic castration-resistant prostate cancer have opened up new scenarios for future patients' management. Defining the best sequencing strategies for men with prostate cancer is a currently unmet medical need, and choosing treatment is often challenging for clinicians because of the lack of direct comparisons of the available agents. The aim of this paper is to provide a comprehensive review of the literature concerning current sequencing strategies for prostate cancer patients.
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Affiliation(s)
- Orazio Caffo
- Department of Medical Oncology, Santa Chiara Hospital, Trento 38112, Italy
| | - Francesca Maines
- Department of Medical Oncology, Santa Chiara Hospital, Trento 38112, Italy
| | | | - Antonello Veccia
- Department of Medical Oncology, Santa Chiara Hospital, Trento 38112, Italy
| | - Carlo Messina
- Department of Medical Oncology, Santa Chiara Hospital, Trento 38112, Italy
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22
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Mignard X, Ruppert AM, Lavolé A, Vieira T, Rozensztajn N, Cadranel J, Wislez M. Is chemotherapy rechallenge feasible in advanced-stage non-small-cell lung cancer? Bull Cancer 2019; 106:725-733. [PMID: 31202557 DOI: 10.1016/j.bulcan.2019.04.010] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/21/2018] [Revised: 12/02/2018] [Accepted: 04/27/2019] [Indexed: 10/26/2022]
Abstract
BACKGROUND Despite recent progress, non-small cell lung cancer (NSCLC) first-line treatment remains a platinum-based doublet in most cases. No guidelines exist beyond third line. Chemotherapy rechallenge is an option, but little data is available in NSCLC. Our study aims to describe patients who underwent chemotherapy rechallenge while assessing its efficacy and safety. METHODS Consecutive patients with advanced-stage NSCLC receiving first-line treatment in Tenon hospital in 2011 were included, with a 5-year follow-up. Patients were analyzed according to chemotherapy rechallenge or not. Chemotherapy rechallenge was defined as re-initiation of a previously administered chemotherapy agent at any point in the treatment sequence, with at least one treatment regimen between first use and rechallenge. RESULTS Of 149 patients, 18 underwent chemotherapy rechallenge (12%). They were younger (56 vs. 61 years, P=0.04), mostly women (61% vs. 30%, P=0.02), with lepidic adenocarcinoma (23% vs. 3.5%, P=0.03), a better general state of health (100% performance status 0-1 vs. 74%, P=0.04), and fewer cardiovascular comorbidities (16% vs. 42%, P=0.04). They were more likely to have received a receptor tyrosine kinase inhibitor treatment (89% vs. 43%, P=0.0003). Progression-free survival was longer at first use than at rechallenge (median 9.2 vs. 2.7 months, P=0.002). No increased toxicity was observed at rechallenge compared to first use. Finally, a subsequent line of treatment was given after rechallenge in 61% of the patients. CONCLUSION Patients eligible for chemotherapy rechallenge were those with good prognostic factors. Chemotherapy rechallenge may provide a well-tolerated additional line of treatment, with decreased efficacy compared to its first application.
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Affiliation(s)
- Xavier Mignard
- Sorbonne université, UPMC Univ Paris 06, GRC n(o) 04, Theranoscan, 75252 Paris, France
| | - Anne-Marie Ruppert
- AP-HP, Tenon university hospital, pneumology department, 75970 Paris, France
| | - Armelle Lavolé
- AP-HP, Tenon university hospital, pneumology department, 75970 Paris, France
| | - Thibault Vieira
- Institut Mutualiste Montsouris, pneumology department, Paris, France
| | | | - Jacques Cadranel
- AP-HP, Tenon university hospital, pneumology department, 75970 Paris, France
| | - Marie Wislez
- AP-HP, Tenon university hospital, pneumology department, 75970 Paris, France; Sorbonne université, UPMC Univ Paris 06, GRC n(o) 04, Theranoscan, 75252 Paris, France.
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23
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Malone S, Shayegan B, Basappa NS, Chi K, Conter HJ, Hamilton RJ, Hotte SJ, Saad F, So AI, Park-Wyllie L, Hew H, McLeod D, Gotto G. Management algorithms for metastatic prostate cancer. Can Urol Assoc J 2019; 14:50-60. [PMID: 31039111 DOI: 10.5489/cuaj.5840] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/19/2022]
Abstract
INTRODUCTION Prostate cancer poses a significant lifetime risk to Canadian men. Treatment for metastatic prostatic cancer (mPCa) is an area of ongoing research with a lack of up-to-date clinical guidance. The multidisciplinary Canadian Genitourinary Research Consortium (GURC) determined that additional guidance focusing on management of mPCa was warranted. METHODS The most up-to-date guidelines, consensus statements, and emerging phase 3 trials were identified and used to inform development of algorithms by a multidisciplinary genitourinary oncology panel outlining recommendations for the management of mPCa. RESULTS A single pan-Canadian guideline and five national and international guidelines or consensus statements published since 2015 were identified, along with two new phase 3 trials and one additional randomized comparison. Iterative GURC discussions led to the development of two mPCa algorithms: the first addressing management of newly diagnosed metastatic castration-sensitive prostate cancer (mCSPC) patients and the second addressing treatment of patients with metastatic castration-resistant prostate cancer (mCRPC). For newly diagnosed mCSPC patients with high-volume/high-risk disease, either docetaxel or abiraterone acetate and prednisone (AAP) added to androgen-deprivation therapy (ADT) is recommended. The addition of radiotherapy to ADT is suggested for those with low-volume disease and/or AAP to ADT for low-volume or low-risk disease. For first-line mCRPC, androgen receptor-axis-targeted (ARAT) therapy is recommended for most patients, while sequencing with docetaxel, radium-223, ARAT therapy, and/or cabazitaxel is recommended for later lines of therapy. CONCLUSIONS Two treatment algorithms were developed for the management of mPC and can be used by multidisciplinary specialist teams to guide treatment.
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Affiliation(s)
- Shawn Malone
- The Ottawa Hospital, University of Ottawa, Ottawa, ON, Canada
| | - Bobby Shayegan
- Juravinski Cancer Centre, McMaster University, Hamilton, ON, Canada
| | - Naveen S Basappa
- Cross Cancer Institute, University of Alberta, Edmonton, AB, Canada
| | - Kim Chi
- BC Cancer Agency, Vancouver, BC, Canada
| | - Henry J Conter
- William Osler Health System, University of Western Ontario, Brampton, ON, Canada
| | - Robert J Hamilton
- Princess Margaret Cancer Centre, University of Toronto, Toronto, ON, Canada
| | | | - Fred Saad
- Centre Hospitalier de l'Université de Montréal, Montreal, QC, Canada
| | - Alan I So
- Vancouver Prostate Centre, University of British Columbia, Vancouver, BC, Canada
| | | | - Huong Hew
- Medical Affairs, Janssen Inc., Toronto, ON, Canada
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24
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Therapeutic options for first-line metastatic castration-resistant prostate cancer: Suggestions for clinical practise in the CHAARTED and LATITUDE era. Cancer Treat Rev 2019; 74:35-42. [DOI: 10.1016/j.ctrv.2019.01.002] [Citation(s) in RCA: 21] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/21/2018] [Revised: 01/03/2019] [Accepted: 01/04/2019] [Indexed: 12/11/2022]
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Gafita A, Rauscher I, Retz M, Knorr K, Heck M, Wester HJ, D'Alessandria C, Weber WA, Eiber M, Tauber R. Early Experience of Rechallenge 177Lu-PSMA Radioligand Therapy After an Initial Good Response in Patients with Advanced Prostate Cancer. J Nucl Med 2018; 60:644-648. [PMID: 30442756 DOI: 10.2967/jnumed.118.215715] [Citation(s) in RCA: 22] [Impact Index Per Article: 3.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/06/2018] [Accepted: 10/10/2018] [Indexed: 02/06/2023] Open
Abstract
Our aim was to retrospectively evaluate the feasibility of rechallenge 177Lu-prostate-specific membrane antigen (177Lu-PSMA) radioligand therapy. Methods: Rechallenge radioligand therapy was defined as subsequent treatment with 177Lu-PSMA after initial exposure with an excellent response followed by progression. Biochemical, radiographic, clinical antitumor response, and adverse events were analyzed. Prostate-specific antigen (PSA) progression-free survival (PFS) and overall survival were calculated. Results: Eight patients underwent a median of 2 (range: 1-4) cycles of rechallenge with 177Lu-PSMA for imaging and therapy. A maximum PSA decrease of 50% was achieved in 3 patients (37.5%). Radiographic response was favorable in 3 patients, whereas 4 exhibited progressive disease. Eastern Cooperative Oncology Group performance status was stable during therapy in all patients. No grade 4 toxicity was noticed, and grade 3 toxicity occurred in 3 patients (37.5%). The median PSA-PFS and overall survival were 3.2 mo (95% confidence interval, 2.6-3.7 mo) and 14.0 mo (95% confidence interval, 6.2-21.8 mo), respectively. Conclusion: In a small patient cohort with an initial excellent response, 177Lu-PSMA rechallenge is still active, with lower efficacy and higher toxicity.
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Affiliation(s)
- Andrei Gafita
- Department of Nuclear Medicine, Klinikum rechts der Isar, Technical University Munich, Munich, Germany
| | - Isabel Rauscher
- Department of Nuclear Medicine, Klinikum rechts der Isar, Technical University Munich, Munich, Germany
| | - Margitta Retz
- Department of Urology, Klinikum rechts der Isar, Technical University Munich, Munich, Germany; and
| | - Karina Knorr
- Department of Nuclear Medicine, Klinikum rechts der Isar, Technical University Munich, Munich, Germany
| | - Matthias Heck
- Department of Urology, Klinikum rechts der Isar, Technical University Munich, Munich, Germany; and
| | - Hans-Jürgen Wester
- Chair of Pharmaceutical Radiochemistry, Technical University of Munich, Munich, Germany
| | - Calogero D'Alessandria
- Department of Nuclear Medicine, Klinikum rechts der Isar, Technical University Munich, Munich, Germany
| | - Wolfgang A Weber
- Department of Nuclear Medicine, Klinikum rechts der Isar, Technical University Munich, Munich, Germany
| | - Matthias Eiber
- Department of Nuclear Medicine, Klinikum rechts der Isar, Technical University Munich, Munich, Germany
| | - Robert Tauber
- Department of Urology, Klinikum rechts der Isar, Technical University Munich, Munich, Germany; and
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26
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Thomas C, Brandt MP, Baldauf S, Tsaur I, Frees S, Borgmann H, Jäger W, Bartsch G, Schneider M, Dotzauer R, Neisius A, Haferkamp A. Docetaxel-rechallenge in castration-resistant prostate cancer: defining clinical factors for successful treatment response and improvement in overall survival. Int Urol Nephrol 2018; 50:1821-1827. [PMID: 30120678 DOI: 10.1007/s11255-018-1963-1] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/10/2018] [Accepted: 08/12/2018] [Indexed: 11/30/2022]
Abstract
PURPOSE The purpose of the study was to define clinical factors for successful treatment response and re-exposure to docetaxel in metastatic castration-resistant prostate cancer (mCRPC). METHODS An mCRPC database of patients receiving first-line docetaxel and rechallenge courses was established. Several clinical factors were evaluated for prediction of treatment response. Multivariate cox-regression analysis was used to define pre-treatment and treatment factors for survival. RESULTS Between 2005 and 2013, 94 patients with mCRPC were treated with docetaxel. Full data set and follow-up were available for 62 patients. Median follow-up was 84 m [interquartile range (IQR) 64-104 m]. Median biochemical progression-free survival (bPFS) and overall survival under docetaxel were 9 m (IQR 5-16 m) and 20 m (IQR 16-26 m), respectively. Partial PSA-response at first docetaxel-sequence (n = 62), rechallenge (n = 32), and third-sequence (n = 22) docetaxel was 48.4%, 31.6%, and 34.8%, respectively. Time from start of primary androgen deprivation to CRPC > 47 m was the only independent pre-treatment parameter to predict improved overall survival (Hazard Ratio 0.48, p = 0.015). Interestingly, there was a strong trend for improved overall survival in patients with high Gleason Score (Hazard Ratio 0.58; p = 0.08). Partial PSA-response at docetaxel-rechallenge (Hazard Ratio 0.31; p = 0.008) and treatment-free interval > 3 m (Hazard Ratio 3.49; p = 0.014) were the only independent predictive factors under taxane treatment for overall survival. CONCLUSION Despite novel hormonal drugs, docetaxel still plays an important role in the treatment of mCRPC. Patients with partial-PSA-response at rechallenge or a treatment-free interval > 3 m benefit most from docetaxel re-exposure.
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Affiliation(s)
- Christian Thomas
- Department of Urology, University of Mainz, Langenbeckstraße 1, 55131, Mainz, Germany.
| | - Maximilian P Brandt
- Department of Urology, University of Mainz, Langenbeckstraße 1, 55131, Mainz, Germany
| | - Stephanie Baldauf
- Department of Urology, University of Mainz, Langenbeckstraße 1, 55131, Mainz, Germany
| | - Igor Tsaur
- Department of Urology, University of Mainz, Langenbeckstraße 1, 55131, Mainz, Germany
| | - Sebastian Frees
- Department of Urology, University of Mainz, Langenbeckstraße 1, 55131, Mainz, Germany
| | - Hendrik Borgmann
- Department of Urology, University of Mainz, Langenbeckstraße 1, 55131, Mainz, Germany
| | - Wolfgang Jäger
- Department of Urology, University of Mainz, Langenbeckstraße 1, 55131, Mainz, Germany
| | - Georg Bartsch
- Department of Urology, University of Mainz, Langenbeckstraße 1, 55131, Mainz, Germany
| | - Meike Schneider
- Department of Urology, University of Mainz, Langenbeckstraße 1, 55131, Mainz, Germany
| | - Robert Dotzauer
- Department of Urology, University of Mainz, Langenbeckstraße 1, 55131, Mainz, Germany
| | - Andreas Neisius
- Department of Urology, University of Mainz, Langenbeckstraße 1, 55131, Mainz, Germany
| | - Axel Haferkamp
- Department of Urology, University of Mainz, Langenbeckstraße 1, 55131, Mainz, Germany
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Abstract
PURPOSE OF REVIEW To update treatment options and considerations for castration-resistant prostate cancer with specific attention to sequencing of agents based on available evidence and treatment rationale. RECENT FINDINGS The newest research developments over the last several years include multicenter studies that address the sequencing of therapies to improve the treatment of metastatic castration-resistant prostate cancer. Chemotherapy agents, as well as androgen receptor antagonists, are evolving, and there are new tests available to define which patients are more likely to benefit. In addition, there have been some additional trials looking into the safety and efficacy of combination treatment and new therapies. There are multiple factors that should be considered to determine the sequence and/or combinations of therapies for metastatic castration-resistant prostate cancer that can improve quality of life and survival. Promising novel agents in combination with personalized medicine will likely continue to improve treatment of these patients.
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28
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Thibault C, Eymard JC, Birtle A, Krainer M, Baciarello G, Fléchon A, Le Moulec S, Spaeth D, Laguerre B, Caffo O, Deville JL, Beuzeboc P, Hasbini A, Gross-Goupil M, Helissey C, Bennamoun M, Hardy-Bessard AC, Oudard S. Efficacy of cabazitaxel rechallenge in heavily treated patients with metastatic castration-resistant prostate cancer. Eur J Cancer 2018; 97:41-48. [PMID: 29636272 DOI: 10.1016/j.ejca.2018.03.008] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/03/2018] [Revised: 02/23/2018] [Accepted: 03/09/2018] [Indexed: 01/24/2023]
Abstract
BACKGROUND Treatment option in patients with metastatic castration-resistant prostate cancer (mCRPC) previously treated with docetaxel (DOC), cabazitaxel (CABA) and new hormone therapy (NHT) is limited. Rechallenge with DOC is limited because of cumulative toxicities. This study investigated the activity and safety of CABA rechallenge in mCRPC. PATIENTS AND METHODS Clinical data were collected retrospectively in 17 centres in Europe. Eligible patients had undergone rechallenge with cabazitaxel after three previous lines of treatment (DOC, NHT and CABA, in any order). Overall survival (OS) and progression-free survival (PFS) were estimated by the Kaplan-Meier method. Data on toxicities were collected. RESULTS A total of 69 of 562 patients (Eastern Cooperative Oncology Group performance status 0-1 69%) were rechallenged with CABA (25 mg/m2 q3w, 58%; 20 mg/m2 q3w, 27.5%; other, 14.5%) for 1-10 (median 6) cycles; 76.8% received prophylactic granulocyte colony-stimulating factor. Median radiological or clinical PFS with CABA rechallenge was 7.8 months and 11.9 months with initial CABA therapy. OS was 13.7 months (95% confidence interval [CI]: 9.3-15.7) from the first CABA rechallenge cycle, 59.9 months (47.8-67.1) from the first life-extending therapy in mCRPC and 78.3 months (66.4-90.7) from mCRPC diagnosis. Best clinical benefit was improved (34.3%) or stable (47.8%). Lack of response to rechallenge occurred in 17.9% of patients (3.1% with initial CABA). The level of prostate-specific antigen decreased by ≥ 50% in 24% of patients at rechallenge (71% with initial CABA). There was no grade ≥III peripheral neuropathy or nail disorders. CONCLUSIONS CABA rechallenge may be a treatment option without cumulative toxicity in heavily pretreated patients with mCRPC who are still fit and had a progression >3 months after the last CABA injections.
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Affiliation(s)
- Constance Thibault
- European Georges Pompidou Hospital, Paris, France; René Descartes University, Paris V, France
| | | | | | | | | | | | | | | | | | - Orazio Caffo
- Department of Medical Oncology Santa Chiara Hospital, Trento, Italy
| | | | | | - Ali Hasbini
- Oncology Center Clinique Pasteur, Brest, France
| | | | - Carole Helissey
- Hôpital D'Instruction des Armées, Bégin, Saint Mandé, France
| | | | | | - Stéphane Oudard
- European Georges Pompidou Hospital, Paris, France; René Descartes University, Paris V, France.
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29
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Szarvas T, Sevcenco S, Módos O, Keresztes D, Nyirády P, Csizmarik A, Ristl R, Puhr M, Hoffmann MJ, Niedworok C, Hadaschik B, Maj-Hes A, Shariat SF, Kramer G. Matrix metalloproteinase 7, soluble Fas and Fas ligand serum levels for predicting docetaxel resistance and survival in castration-resistant prostate cancer. BJU Int 2018; 122:695-704. [PMID: 29802777 DOI: 10.1111/bju.14415] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/28/2023]
Abstract
OBJECTIVE To assess the predictive value of pre-chemotherapy matrix metalloproteinase 7 (MMP-7), soluble Fas (sFas) and Fas ligand (FasL) serum levels, as well as their changes during therapy. PATIENTS AND METHODS Serum levels of MMP-7, Fas and FasL were determined by ELISA in 96 patients with castration-resistant prostate cancer (CRPC): 21 docetaxel-resistant patients who received one single series and 75 docetaxel-sensitive patients who received repeated series of docetaxel. In addition to the 96 pretreatment serum samples, 987 sera collected during chemotherapy were also analysed. RESULTS Higher pretreatment serum MMP-7, sFas and prostate-specific antigen (PSA) levels were significantly associated with both docetaxel resistance (P = 0.007, P = 0.001, P < 0.001, respectively) and shorter cancer-specific survival (P < 0.001, P = 0.041, P < 0.001, respectively). High MMP-7 level remained an independent predictor of both docetaxel resistance (hazard ratio [HR] 2.298, 95% confidence interval [CI]: 1.354-3.899; P = 0.002) and poor cancer-specific survival (HR 2.11, 95% CI: 1.36-3.30; P = 0.001) in multivariable analyses. Greater increase in MMP-7 levels in the second treatment holiday and greater increase in PSA levels in the first and second treatment holidays were predictive of survival. CONCLUSIONS Pretreatment serum MMP-7 levels may help to select patients with CRPC who are likely to benefit from docetaxel chemotherapy. Furthermore, MMP-7 levels alone or in combination with PSA levels could be used for therapy monitoring. Correlative studies embedded in clinical trials are necessary to validate these biomarkers for clinical decision-making.
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Affiliation(s)
- Tibor Szarvas
- Department of Urology, Semmelweis University, Budapest, Hungary.,Department of Urology, Vienna General Hospital, Medical University Vienna, Vienna, Austria.,Department of Urology, Faculty of Medicine, University Duisburg-Essen, Essen, Germany
| | - Sabina Sevcenco
- Department of Urology, Vienna General Hospital, Medical University Vienna, Vienna, Austria
| | - Orsolya Módos
- Department of Urology, Semmelweis University, Budapest, Hungary
| | - Dávid Keresztes
- Department of Urology, Semmelweis University, Budapest, Hungary
| | - Péter Nyirády
- Department of Urology, Semmelweis University, Budapest, Hungary
| | - Anita Csizmarik
- Department of Urology, Semmelweis University, Budapest, Hungary
| | - Robin Ristl
- Centre for Medical Statistics, Informatics, and Intelligent Systems, Medical University of Vienna, Vienna, Austria
| | - Martin Puhr
- Experimental Urology, Department of Urology, Medical University of Innsbruck, Innsbruck, Austria
| | - Michèle J Hoffmann
- Department of Urology, Medical Faculty, Heinrich-Heine-University Düsseldorf, Düsseldorf, Germany
| | - Christian Niedworok
- Department of Urology, Faculty of Medicine, University Duisburg-Essen, Essen, Germany
| | - Boris Hadaschik
- Department of Urology, Faculty of Medicine, University Duisburg-Essen, Essen, Germany
| | - Agnieszka Maj-Hes
- Department of Urology, Vienna General Hospital, Medical University Vienna, Vienna, Austria
| | - Shahrokh F Shariat
- Department of Urology, Vienna General Hospital, Medical University Vienna, Vienna, Austria
| | - Gero Kramer
- Department of Urology, Vienna General Hospital, Medical University Vienna, Vienna, Austria
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30
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Cash H, Steiner U, Heidenreich A, Klotz T, Albers P, Melchior S, Martus P, Fuller F, Magheli A, Hinz S, Kempkensteffen C, Miller K. Intermittent vs continuous docetaxel therapy in patients with metastatic castration-resistant prostate cancer - a phase III study (PRINCE). BJU Int 2018; 122:774-782. [PMID: 29633515 DOI: 10.1111/bju.14239] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/29/2022]
Abstract
OBJECTIVE To investigate non-inferiority of intermittent docetaxel compared to continuous docetaxel in patients with metastatic castration-resistant prostate cancer (mCRPC). PATIENT AND METHODS The investigator initiated randomised phase III study included 187 chemotherapy-naïve patients with mCRPC who were allocated to two treatment arms: intermittent docetaxel and continuous docetaxel. Docetaxel was applied in both arms as weekly (35 mg/m2 ) or 3-weekly (75 mg/m2 ). The primary endpoint was 1-year survival, which was tested for non-inferiority (margin δ = 0.125). The secondary endpoints were: overall survival (OS), progression-free survival (PFS), median time to treatment failure (TTF), and toxicity. RESULTS Of 156 eligible patients, 78 were allocated to each arm. The intermittent treatment met the non-inferiority criteria for 1-year survival (two-sided 95% confidence interval, -0.12, 18, P = 0.022), but not for OS, according to the result of a post hoc analysis. The differences between the study arms in PFS and TTF were not significant. The median (range) treatment holiday in the intermittent arm was 110 (13-486) days, or 38% of the overall treatment duration. Safety profiles of both study arms were comparable. The main limitation of this study was that the planned number of patients could not be recruited. CONCLUSION Intermittent docetaxel chemotherapy was non-inferior to continuous therapy for 1-year survival; non-inferiority in regard to OS was not reached.
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Affiliation(s)
- Hannes Cash
- Department of Urology, Charité, University Medicine Berlin, Berlin, Germany
| | - Ursula Steiner
- Department of Urology, Charité, University Medicine Berlin, Berlin, Germany
| | - Axel Heidenreich
- Department of Urology, University Hospital Cologne, Cologne, Germany
| | - Theodor Klotz
- Department of Urology, Weiden Hospital, Weiden, Germany
| | - Peter Albers
- Department of Urology, University Hospital Düsseldorf, Düsseldorf, Germany
| | | | - Peter Martus
- Institute for Clinical Epidemiology and Applied Biometrics, Tübingen University Hospital, Tübingen, Germany
| | - Florian Fuller
- Department of Urology, Charité, University Medicine Berlin, Berlin, Germany
| | - Ahmed Magheli
- Department of Urology, Charité, University Medicine Berlin, Berlin, Germany
| | - Stefan Hinz
- Department of Urology, Charité, University Medicine Berlin, Berlin, Germany
| | | | - Kurt Miller
- Department of Urology, Charité, University Medicine Berlin, Berlin, Germany
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Lavaud P, Gravis G, Foulon S, Joly F, Oudard S, Priou F, Latorzeff I, Mourey L, Soulié M, Delva R, Krakowski I, Laguerre B, Théodore C, Ferrero JM, Beuzeboc P, Habibian M, Rolland F, Deplanque G, Pouessel D, Zanetta S, Berdah JF, Dauba J, Baciuchka M, Platini C, Linassier C, Tubiana-Mathieu N, Machiels JP, Kouri CE, Ravaud A, Suc E, Eymard JC, Hasbini A, Bousquet G, Culine S, Boher JM, Tergemina-Clain G, Legoupil C, Fizazi K. Anticancer Activity and Tolerance of Treatments Received Beyond Progression in Men Treated Upfront with Androgen Deprivation Therapy With or Without Docetaxel for Metastatic Castration-naïve Prostate Cancer in the GETUG-AFU 15 Phase 3 Trial. Eur Urol 2018; 73:696-703. [DOI: 10.1016/j.eururo.2017.09.022] [Citation(s) in RCA: 43] [Impact Index Per Article: 6.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/22/2017] [Accepted: 09/19/2017] [Indexed: 12/19/2022]
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Mansinho A, Macedo D, Fernandes I, Costa L. Castration-Resistant Prostate Cancer: Mechanisms, Targets and Treatment. ADVANCES IN EXPERIMENTAL MEDICINE AND BIOLOGY 2018; 1096:117-133. [PMID: 30324351 DOI: 10.1007/978-3-319-99286-0_7] [Citation(s) in RCA: 73] [Impact Index Per Article: 10.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/14/2022]
Abstract
Prostate cancer is the most common malignancy in men, and remains the second leading cause of cancer-related death in this gender [1]. Data suggests that 10-20% of patients with prostate cancer metastasis develop castration-resistant prostate cancer (CRPC) within 5 years of follow-up, and that the median survival since development of castration resistance is approximately 14 months (range 9-30) [2]. Additionally, patients with non-metastatic CRPC are at higher risk of disease progression. Approximately 15-33% of patients develop metastasis within 2 years, increasing the mortality burden in this population [3, 4].
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Affiliation(s)
- André Mansinho
- Oncology Department, Hospital de Santa Maria, Centro Hospitalar Lisboa Norte, Lisbon, Portugal
| | - Daniela Macedo
- Oncology Department, Hospital de Santa Maria, Centro Hospitalar Lisboa Norte, Lisbon, Portugal
| | - Isabel Fernandes
- Department of Oncology, Hospital de Santa Maria, Centro Hospitalar Lisboa Norte, Lisbon, Portugal.,Oncology Division, Faculdade de Medicina de Lisboa, Instituto de Medicina Molecular, Lisbon, Portugal
| | - Luís Costa
- Department of Oncology, Hospital de Santa Maria, Centro Hospitalar Lisboa Norte, Lisbon, Portugal. .,Oncology Division, Faculdade de Medicina de Lisboa, Instituto de Medicina Molecular, Lisbon, Portugal.
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Bouman-Wammes EW, van den Berg HP, de Munck L, Beeker A, Smorenburg CH, Vervenne WL, Coenen JLLM, Verheul HMW, Gerritsen WR, Van den Eertwegh AJM. A randomised phase II trial of docetaxel versus docetaxel plus carboplatin in patients with castration-resistant prostate cancer who have progressed after response to prior docetaxel chemotherapy: The RECARDO trial. Eur J Cancer 2017; 90:1-9. [PMID: 29268139 DOI: 10.1016/j.ejca.2017.11.021] [Citation(s) in RCA: 16] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/14/2017] [Revised: 11/09/2017] [Accepted: 11/20/2017] [Indexed: 11/18/2022]
Abstract
BACKGROUND Docetaxel is standard first-line chemotherapy for patients with metastatic castration-resistant prostate carcinoma (mCRPC). Docetaxel re-challenge has never been tested in a prospective randomised controlled study. As some studies support the addition of carboplatin to docetaxel, we performed a phase II trial investigating the combination of docetaxel plus carboplatin versus docetaxel re-treatment in docetaxel pre-treated mCRPC patients. METHODS Patients with mCRPC with a progression-free interval of ≥3 months after initial docetaxel treatment were randomised between docetaxel 75 mg/m2 or docetaxel 60 mg/m2 plus carboplatin AUC4. The primary end-point was progression-free survival (PFS; PSA/RECIST). RESULTS Owing to insufficient recruitment, the study was discontinued early after inclusion of 75 patients (targeted 150) PFS and overall survival (OS) were comparable between both groups (median PFS 12.7 months (95% CI 9.9-17.5 months) with docetaxel monotherapy and 11.7 months (95% CI 8.5-21.0 months) with combination therapy (p = 0.98); OS 18.5 months (95% CI 11.8-24.5 months) versus 18.9 months (95% CI 16.0-23.7 months) (p = 0.79). An interim analysis (SEQTEST) showed that the null hypothesis could already be excepted, and no significant difference between both study arms was expected if inclusion would be completed. The incidence of grade 3-4 infections and gastrointestinal side-effects was numerical higher in the carboplatin arm (p = 0.056). CONCLUSION This early terminated study suggests no benefit from the addition of carboplatin to docetaxel re-treatment in patients with mCRPC, whereas the combination resulted in more toxicity. Re-treatment with docetaxel monotherapy appears to be feasible, save and effective for patients with mCRPC and an initial good response to docetaxel. TRIAL REGISTRATION NTR3070.
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Affiliation(s)
- Esther W Bouman-Wammes
- Department of Medical Oncology, VU University Medical Center, Amsterdam, The Netherlands.
| | | | - Linda de Munck
- Department of Research, Netherlands Comprehensive Cancer Organisation, Utrecht, The Netherlands
| | - Aart Beeker
- Department of Medical Oncology, Spaarne Gasthuis, Hoofddorp, The Netherlands
| | | | - Walter L Vervenne
- Department of Medical Oncology, Deventer ziekenhuis, Deventer, The Netherlands
| | | | - Henk M W Verheul
- Department of Medical Oncology, VU University Medical Center, Amsterdam, The Netherlands
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Hoshi S, Numahata K, Ono K, Yasuno N, Bilim V, Hoshi K, Amemiya H, Sasagawa I, Ohta S. Treatment sequence in castration-resistant prostate cancer: A retrospective study in the new anti-androgen era. Mol Clin Oncol 2017; 7:601-603. [PMID: 28855993 DOI: 10.3892/mco.2017.1361] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/10/2017] [Accepted: 05/16/2017] [Indexed: 01/07/2023] Open
Abstract
In recent years, abiraterone acetate (AA) and enzalutamide (EZL) have become available for the treatment of cancer. Prior clinical trials have demonstrated the benefits of these agents in males with castration-resistant prostate cancer (CRPC). The optimal sequencing of available therapies in the context of efficacy and known cross-resistance remains uncertain. Based on the mechanisms of action and accessible clinical data, AA and EZL may be indicated for the early stages of prostate cancer. Until clinical trials are conducted to determine the best treatment sequence, individualized therapy is required for each patient based on the clinicopathological characteristics. In the present study, 46 sequential patients (median age: 77, range 59-89; median serum PSA level: 56 ng/ml, range 1.5-3,211) with CRPC treated with EZL (160 mg/day) were retrospectively analyzed between June 2014 and July 2015 at the following institutions: Yamagata Prefectural Central Hospital (Yamagata, Japan); Yamagata Tokushukai Hospital (Yamagata, Japan); Ishinomaki Red Cross Hospital (Ishinomaki, Japan); Kan-etsu Hospital (Tsurugashima, Japan); Niigata Cancer Center Hospital (Niigata, Japan); Sakado Central Hospital (Sakado, Japan). A total of 18 patients were pre-treated with Docetaxel (DOC) and 28 patients were DOC-naïve. Once EZL therapy was initiated, increases in prostate specific antigen (PSA) levels were observed in 3/18 patients (17%) pre-treated with DOC and in 6/20 (30%) who were DOC-naïve. In total, 8/28 DOC-naïve patients were treated with AA without EZL. An increase in the PSA level was observed in only 1/8 (12%) cases following AA treatment in the DOC-naïve group. It was demonstrated that AA had a better efficacy in DOC-naïve patients. The efficacy of EZL was limited in AA-pre-treated patients following DOC administration.
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Affiliation(s)
- Senji Hoshi
- Department of Urology, Yamagata Prefectural Central Hospital, Yamagata 990-2214, Japan.,Department of Urology, Yamagata Tokushukai Hospital, Yamagata 990-0834, Japan
| | - Kenji Numahata
- Department of Urology, Yamagata Prefectural Central Hospital, Yamagata 990-2214, Japan
| | - Kunio Ono
- Department of Urology, Ishinomaki Red Cross Hospital, Ishinomaki, Miyagi 986-0861, Japan
| | - Nobuhiro Yasuno
- Department of Pharmacy, Kan-etsu Hospital, Tsurugashima, Saitama 350-2213, Japan
| | - Vladimir Bilim
- Department of Urology, Niigata Cancer Center Hospital, Niigata 951-8133, Japan
| | - Kiyotsugu Hoshi
- Department of Urology, Yamagata Tokushukai Hospital, Yamagata 990-0834, Japan
| | - Hiroshi Amemiya
- Department of Urology, Sakado Central Hospital, Sakado, Saitama 350-0233, Japan
| | - Isoji Sasagawa
- Department of Urology, Yamagata Tokushukai Hospital, Yamagata 990-0834, Japan
| | - Shoichiro Ohta
- Department of Clinical Pathology, Faculty of Pharmaceutical Science, Josai University, Sakado, Saitama 350-0295, Japan
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Picciotto M, Franchina T, Russo A, Ricciardi GRR, Provazza G, Sava S, Baldari S, Caffo O, Adamo V. Emerging role of Radium-223 in the growing therapeutic armamentarium of metastatic castration-resistant prostate cancer. Expert Opin Pharmacother 2017; 18:899-908. [DOI: 10.1080/14656566.2017.1323875] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/29/2022]
Affiliation(s)
- Maria Picciotto
- Medical Oncology Unit A.O. Papardo & Department of Human Pathology, University of Messina, Messina, Italy
| | - Tindara Franchina
- Medical Oncology Unit A.O. Papardo & Department of Human Pathology, University of Messina, Messina, Italy
| | - Alessandro Russo
- Medical Oncology Unit A.O. Papardo & Department of Human Pathology, University of Messina, Messina, Italy
| | | | - Giusy Provazza
- Medical Oncology Unit A.O. Papardo & Department of Human Pathology, University of Messina, Messina, Italy
| | - Serena Sava
- Medical Oncology Unit A.O. Papardo & Department of Human Pathology, University of Messina, Messina, Italy
| | - Sergio Baldari
- Department of Biomedical and Dental Sciences and of Morphological and Functional Images, University of Messina, Messina, Italy
| | - Orazio Caffo
- Medical Oncology Department, Santa Chiara Hospital, Trento, Italy
| | - Vincenzo Adamo
- Medical Oncology Unit A.O. Papardo & Department of Human Pathology, University of Messina, Messina, Italy
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Oudard S, Maroto P, Demonty G, Gerritsen WR. Charting Recent Progress and Challenges in Metastatic Castration-resistant Prostate Cancer: Is There an Optimal Treatment Sequence? Eur Urol Focus 2016; 2:426-440. [DOI: 10.1016/j.euf.2015.11.008] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/20/2015] [Revised: 11/04/2015] [Accepted: 11/23/2015] [Indexed: 12/14/2022]
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Kongsted P, Svane IM, Lindberg H, Sengeløv L. Clinical Impact of the Number of Treatment Cycles in First-Line Docetaxel for Patients With Metastatic Castration-Resistant Prostate Cancer. Clin Genitourin Cancer 2016; 15:e281-e287. [PMID: 27692811 DOI: 10.1016/j.clgc.2016.08.019] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/30/2016] [Revised: 08/12/2016] [Accepted: 08/26/2016] [Indexed: 12/11/2022]
Abstract
BACKGROUND We investigated the impact of the number of docetaxel cycles administered in patients with metastatic castration-resistant prostate cancer (mCRPC) treated with first-line chemotherapy. PATIENTS AND METHODS Charts from 421 consecutive patients who initiated standard treatment with docetaxel-based chemotherapy (75 mg/m2 every 3 weeks) between 2007 and 2013 were reviewed. Patients who received < 6 cycles of docetaxel were excluded from the analysis. Remaining patients were divided into 2 groups on the basis of whether or not ≥ 9 cycles of docetaxel were administered (n = 108 and 184, respectively). Reasons for treatment discontinuation and postdocetaxel treatments were registered. Prostate-specific antigen (PSA) responses were defined as a confirmed ≥ 50% decrease in baseline PSA levels. Overall survival (OS) was calculated from start of therapy using the Kaplan-Meier method. Cox proportional hazards were calculated to estimate the effect of clinical variables on OS. RESULTS OS was longer in patients treated with ≥ 9 cycles of docetaxel (21.9 months vs. 17.2 months; P < .0001, log rank). Survival also favored patients treated with ≥ 9 cycles of docetaxel when only patients ending docetaxel because of toxicity or treatment conclusion (22.3 vs. 19.4 months; P = .048, log rank) or patients who achieved a PSA response (22.3 vs. 18.7 months; P = .012, log rank) were evaluated. mCRPC-related prognostic factors and patients who received ≥ 1 subsequent line of therapy post-docetaxel were well balanced. CONCLUSION On the basis of our retrospective findings, a superior OS was found in patients treated with ≥ 9 cycles of docetaxel when adjusting for known prognostic factors. Dose reductions might increase the number of docetaxel cycles administered.
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Affiliation(s)
- Per Kongsted
- Department of Oncology, Herlev University Hospital, Herlev, Denmark.
| | - Inge Marie Svane
- Department of Oncology, Herlev University Hospital, Herlev, Denmark
| | | | - Lisa Sengeløv
- Department of Oncology, Herlev University Hospital, Herlev, Denmark
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Daste A, Gross-Goupil M, Quivy A, François L, Bernhard JC, Ravaud A. Efficacy of Rechallenge of Metastatic Renal Cell Carcinoma Patient With Sunitinib After Prior Resistance to Axitinib: Case Report and Review of the Literature. Clin Genitourin Cancer 2016; 14:e525-e527. [PMID: 27185091 DOI: 10.1016/j.clgc.2016.04.009] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/20/2016] [Accepted: 04/11/2016] [Indexed: 01/15/2023]
Affiliation(s)
- Amaury Daste
- Department of Medical Oncology, Hôpital Saint-André, University of Bordeaux-CHU Bordeaux, France; University of Bordeaux, Bordeaux, France.
| | - Marine Gross-Goupil
- Department of Medical Oncology, Hôpital Saint-André, University of Bordeaux-CHU Bordeaux, France
| | - Amandine Quivy
- Department of Medical Oncology, Hôpital Saint-André, University of Bordeaux-CHU Bordeaux, France
| | - Louis François
- Department of Medical Oncology, Hôpital Saint-André, University of Bordeaux-CHU Bordeaux, France; University of Bordeaux, Bordeaux, France
| | | | - Alain Ravaud
- Department of Medical Oncology, Hôpital Saint-André, University of Bordeaux-CHU Bordeaux, France; University of Bordeaux, Bordeaux, France
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Di Lorenzo G, Pagliuca M, Perillo T, Benincasa A, Bosso D, De Placido S, Buonerba C. Docetaxel Rechallenge in a Heavily Pretreated Patient With Castration-Resistant Prostate Cancer: A Case Report and Review of Literature. Medicine (Baltimore) 2016; 95:e2754. [PMID: 27057826 PMCID: PMC4998742 DOI: 10.1097/md.0000000000002754] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/30/2022] Open
Abstract
Chemotherapy agents for patients with metastatic castration-resistant prostate cancer (mCRPC) include docetaxel and cabazitaxel. Although docetaxel is approved in the first-line treatment setting, a few studies have shown that selected patients can benefit from docetaxel rechallenge.We, here, report the case of a heavily pretreated mCRPC patient who reported clinical benefit from receiving docetaxel after previous exposure to docetaxel, cabazitaxel, abiraterone, and enzalutamide.After 4 cycles of treatment, patient's performance status had improved to 1, the hemoglobin level was 12.9 g/dL and his serum prostate specific antigen levels were reduced by >70%, with no treatment-related adverse events.Although docetaxel rechallenge is a therapeutic option for selected patients, the risk of cumulative toxicity described in literature must be carefully considered.As the risk of cabazitaxel-related cumulative toxicity is probably lower, retreatment with cabazitaxel rather than docetaxel may also be an option in the setting of heavily pretreated mCRPC patients.
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Affiliation(s)
- Giuseppe Di Lorenzo
- From the Medical Oncology Unit, Department of Clinical Medicine, Federico II University, Naples, Italy
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Di Lorenzo G, Bracarda S, Gasparro D, Gernone A, Messina C, Zagonel V, Puglia L, Bosso D, Dondi D, Sonpavde G, Lucarelli G, De Placido S, Buonerba C. Lack of Cumulative Toxicity Associated With Cabazitaxel Use in Prostate Cancer. Medicine (Baltimore) 2016; 95:e2299. [PMID: 26765406 PMCID: PMC4718232 DOI: 10.1097/md.0000000000002299] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/26/2022] Open
Abstract
Cabazitaxel provided a survival advantage compared with mitoxantrone in patients with castration-resistant prostate cancer refractory to docetaxel. Grade 3 to 4 (G3-4) neutropenia and febrile neutropenia were relatively frequent in the registrative XRP6258 Plus Prednisone Compared to Mitoxantrone Plus Prednisone in Hormone Refractory Metastatic Prostate Cancer (TROPIC) trial, but their incidence was lower in the Expanded Access Program (EAP). Although cumulative doses of docetaxel are associated with neuropathy, the effect of cumulative doses of cabazitaxel is unknown. In this retrospective review of prospectively collected data, the authors assessed "per cycle" incidence and predictors of toxicity in the Italian cohort of the EAP, with a focus on the effect of cumulative doses of cabazitaxel.The study population consisted of 218 Italian patients enrolled in the cabazitaxel EAP. The influence of selected variables on the most relevant adverse events identified was assessed using a Generalized Estimating Equations model at univariate and multivariate analysis."Per cycle" incidence of G 3 to 4 neutropenia was 8.7%, whereas febrile neutropenia was reported in 0.9% of cycles. All events of febrile neutropenia occurred during the first 3 cycles. Multivariate logistic regression analysis showed that higher prior dose of cabazitaxel was associated with decreased odds of having G3 to 4 neutropenia (OR = 0.90; 95% CI: 0.86-0.93; P < 0.01), febrile neutropenia (OR = 0.52; 95% CI: 0.34-0.81; P < 0.01) and G3 to 4 anemia (OR = 0.93; 95% CI: 0.86-1; P = 0.07). Patients with a body surface area >2 m2 presented increased odds of having G 3 to 4 neutropenia (OR = 0.93; 95% CI: 0.86-1; P = 0.07), but decreased odds of having G3 to 4 anemia.Among the toxicities assessed, the authors did not identify any that appeared to be associated with a higher number of cabazitaxel cycles delivered. Prior cumulative dose was associated with reduced G3 to 4 neutropenia and anemia. The apparent protective effect associated with higher doses of cabazitaxel is likely to be affected by early dose reduction and early toxicity-related treatment discontinuation. Because this analysis is limited by its retrospective design, prospective trials are required to assess the optimal duration of cabazitaxel treatment.
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Affiliation(s)
- Giuseppe Di Lorenzo
- From the Department of Clinical Medicine, Federico II University, Naples (GDL, LP, DB, SDP, CB); Department of Oncology, Medical Oncology Unit, San Donato Hospital, Arezzo (SB); Department of Oncohematology, University Hospital of Parma, Parma (DG); Policlinico Hospital, Bari (AG); Ospedale Papa Giovanni Paolo XXIII Hospital, Bergamo (CM); Medical Oncology Unit, Istituto Oncologico Veneto-IRCCS, Padua (VZ); Medical Affairs Oncology Division, Sanofi, Milan, Italy (DD); Department of Medicine, Urologic Oncology, Division of Hematology & Oncology, University of Alabama at Birmingham, Birmingham, AL (GS); and Department of Emergency and Organ Transplantation, Urology, Andrology and Kidney Transplantation Unit, University of Bari, Bari, Italy (GL)
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Herden J, Heidegger I, Paffenholz P, Porres D. Systemic Medical Treatment in Men with Metastatic Castration-Resistant Prostate Cancer: Recommendations for Daily Routine. Oncol Res Treat 2015; 38:654-68. [PMID: 26633646 DOI: 10.1159/000442030] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/09/2015] [Accepted: 10/20/2015] [Indexed: 11/19/2022]
Abstract
The approval or clinical evaluation of several new agents - cabazitaxel, abiraterone acetate, enzalutamide, sipuleucel-T, and radium-223 - has significantly changed the management of patients with metastatic castration-resistant prostate cancer (mCRPC) prior to or after docetaxel-based chemotherapy. All of these agents have resulted in a significant survival benefit as compared to their control group. However, treatment responses might differ depending on the associated comorbidities and the extent and biological aggressiveness of the disease. Furthermore, treatment-associated side effects differ between the various drugs. As new drugs become approved, new treatment strategies and markers to best select which patients will best respond to which drug are needed. It is the aim of the current article to i) summarize the data of established treatment options in mCRPC, ii) highlight new developments in medical treatment, iii) provide clinically useful algorithms for the daily routine, and iv) point out future developments in medical treatment.
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Affiliation(s)
- Jan Herden
- Department of Urology, University Hospital Cologne, Cologne, Germany
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Petrioli R, Francini E, Roviello G. Is there still a place for docetaxel rechallenge in prostate cancer? World J Clin Oncol 2015; 6:99-103. [PMID: 26468445 PMCID: PMC4600198 DOI: 10.5306/wjco.v6.i5.99] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/11/2015] [Revised: 06/15/2015] [Accepted: 07/24/2015] [Indexed: 02/06/2023] Open
Abstract
Three-weekly docetaxel plus prednisone is the standard first-line cytotoxic treatment for patients with metastatic castrate-resistant prostate cancer (mCRPC). Today, several new treatment options are available for patients with tumor progression after first-line docetaxel: Abiraterone, enzalutamide, cabazitaxel, sipuleucel-T immunotherapy, and the radionuclide radium-223. However, despite the evolving scenario in CRPC treatment, the optimal sequencing of the innovative therapies remains unclear. The reintroduction of docetaxel at the occurrence of disease progression after a drug holiday (docetaxel rechallenge) was often proposed, and this chemotherapeutic agent showed to maintain antitumor activity in mCRPC patients. Docetaxel rechallenge may still constitute a valid treatment option mainly for patients with favorable response to first-line docetaxel, at least > 3 mo progression-free interval, age less than 75 years, good performance status, and acceptable docetaxel toxicity. The risk of cumulative toxicity must be evaluated, since sensory neuropathy, nail disorders and fatigue might occur on docetaxel rechallenge.
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Bracarda S, Caserta C, Galli L, Carlini P, Pastina I, Sisani M, Scali S, Hamzaj A, Derosa L, Felici A, Rossi M, Altavilla A, Chioni A, De Angelis V. Docetaxel rechallenge in metastatic castration-resistant prostate cancer: any place in the modern treatment scenario? An intention to treat evaluation. Future Oncol 2015; 11:3083-90. [PMID: 26437324 DOI: 10.2217/fon.15.217] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/21/2022] Open
Abstract
BACKGROUND We evaluated the possible advantages of a docetaxel (DCT) rechallenge strategy in metastatic castration-resistant prostate cancer (mCRPC) patients, also given the possible earlier positioning of this treatment option in the modern scenario. PATIENTS & METHODS All mCRPC patients planned for DCT chemotherapy rechallenge in our institutions were evaluated. RESULTS Of 128 patients, 98 achieved disease control on the initial DCT round. After a treatment holiday of 8.3 months, the 98 responsive patients underwent a second DCT round, with 56 cases achieving again disease control. After a 5.7-month off-treatment period, 32 of these cases underwent a third DCT round, and 16 responded. Lastly, after a further 4.2-month treatment holiday, eight patients underwent a fourth DCT round and two responded. Median time to definitive disease progression for the whole population was 16.4 months. CONCLUSIONS Rechallenge with DCT may be considered a suitable treatment option for mCRPC patients recurring after a successful DCT chemotherapy. The interest in this strategy may be increased because of the showed efficacy of early DCT chemotherapy in patients with bulky disease (CHAARTED study) and the potential lower efficacy of the new hormonal agents abiraterone acetate and enzalutamide when used in a immediate sequencing.
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Affiliation(s)
- Sergio Bracarda
- Medical Oncology, Ospedale San Donato, Azienda USL8, Istituto Toscano Tumori (ITT), Arezzo, Italy
| | - Claudia Caserta
- Medical Oncology, Ospedale S Maria, Terni, Italy.,Medical Oncology, Ospedale della Gruccia, Azienda USL8, Istituto Toscano Tumori (ITT), Arezzo, Italy
| | - Luca Galli
- Medical Oncology, Azienda Ospedaliera Universitaria di Perugia, Perugia, Italy
| | - Paolo Carlini
- Medical Oncology, Azienda Ospedaliero Universitaria Pisana, Istituto Toscano Tumori (ITT), Pisa, Italy
| | | | - Michele Sisani
- Medical Oncology, Ospedale San Donato, Azienda USL8, Istituto Toscano Tumori (ITT), Arezzo, Italy
| | - Simona Scali
- Medical Oncology, Ospedale Misericordia, Istituto Toscano Tumori (ITT), Grosseto, Italy
| | - Alketa Hamzaj
- Medical Oncology, Ospedale San Donato, Azienda USL8, Istituto Toscano Tumori (ITT), Arezzo, Italy.,Medical Oncology, Ospedale della Gruccia, Azienda USL8, Istituto Toscano Tumori (ITT), Arezzo, Italy
| | - Lisa Derosa
- Medical Oncology, Azienda Ospedaliera Universitaria di Perugia, Perugia, Italy
| | - Alessandra Felici
- Medical Oncology, Azienda Ospedaliero Universitaria Pisana, Istituto Toscano Tumori (ITT), Pisa, Italy
| | - Marta Rossi
- Medical Oncology, Ospedale della Gruccia, Azienda USL8, Istituto Toscano Tumori (ITT), Arezzo, Italy
| | - Amelia Altavilla
- Medical Oncology, Ospedale San Donato, Azienda USL8, Istituto Toscano Tumori (ITT), Arezzo, Italy
| | | | - Verena De Angelis
- Medical Oncology, Ospedale della Gruccia, Azienda USL8, Istituto Toscano Tumori (ITT), Arezzo, Italy
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Lorente D, Mateo J, Perez-Lopez R, de Bono JS, Attard G. Sequencing of agents in castration-resistant prostate cancer. Lancet Oncol 2015; 16:e279-92. [PMID: 26065613 DOI: 10.1016/s1470-2045(15)70033-1] [Citation(s) in RCA: 115] [Impact Index Per Article: 11.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
Until 2010, docetaxel was the only agent with proven survival benefit for castration-resistant prostate cancer. The development of cabazitaxel, abiraterone acetate, enzalutamide, radium-223, and sipuleucel-T has increased the number of treatment options. Because these agents were developed concurrently within a short period of time, prospective data on their sequential use efficacy are scarce. The challenge now is to reach a consensus on the best way to sequence effective treatments, ideally by the use of an approach specific to patient subgroups. However, the absence of robust surrogates of survival and the lack of predictive biomarkers makes data for the sequential use of these agents difficult to obtain and interpret.
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Affiliation(s)
- David Lorente
- Prostate Cancer Targeted Therapy Group, The Institute of Cancer Research and the Royal Marsden NHS Foundation Trust, London, UK
| | - Joaquin Mateo
- Prostate Cancer Targeted Therapy Group, The Institute of Cancer Research and the Royal Marsden NHS Foundation Trust, London, UK
| | - Raquel Perez-Lopez
- Prostate Cancer Targeted Therapy Group, The Institute of Cancer Research and the Royal Marsden NHS Foundation Trust, London, UK
| | - Johann S de Bono
- Prostate Cancer Targeted Therapy Group, The Institute of Cancer Research and the Royal Marsden NHS Foundation Trust, London, UK
| | - Gerhardt Attard
- Prostate Cancer Targeted Therapy Group, The Institute of Cancer Research and the Royal Marsden NHS Foundation Trust, London, UK.
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Petrioli R, Roviello G, Fiaschi AI, Laera L, Miano ST, De Rubertis G, Barbanti G, Bianco V, Brozzetti S, Francini E. Rechallenge of docetaxel combined with epirubicin given on a weekly schedule in advanced castration-resistant prostate cancer patients previously exposed to docetaxel and abiraterone acetate: a single-institution experience. Med Oncol 2015; 32:52. [PMID: 25636506 DOI: 10.1007/s12032-015-0485-2] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/22/2014] [Accepted: 01/23/2015] [Indexed: 12/21/2022]
Abstract
The aim of this paper was to evaluate the activity and tolerability of weekly docetaxel (D) combined with weekly epirubicin (EPI) in patients with advanced castrate-resistant prostate cancer (CRPC) previously exposed to D and abiraterone acetate (AA). Locally advanced or metastatic CRPC patients with 0-2 performance status, who had progressed after D and AA therapy, were included in the study. Previous treatment with chemotherapy agent cabazitaxel was also admitted. Treatment consisted of D 30 mg/m(2) intravenously (i.v.) and EPI 30 mg/m(2) i.v., every week (D/EPI). Chemotherapy was administered until disease progression or unacceptable toxicity. In our institution, twenty-six patients received D/EPI: their median age was 72 years (range 59-83 years). Twenty-three (88.5%) patients had bone metastases. A decrease in PSA levels ≥50% was observed in seven patients (26.9%, 95% CI: 0.11-0.47); of these, five had achieved a ≥50% PSA response during prior first-line D and six had achieved a PSA response during prior AA Among the subjects who were symptomatic at baseline, pain was reduced in nine patients (38.1%) with a significant decrease in analgesic use. Median progression-free survival was 4.4 months (95% CI, 3-5.2), and median overall survival was 10.7 months (95% CI, 8.9-18.4). Treatment was well tolerated and no grade 4 toxicities were observed. Our findings suggest that weekly D/EPI is feasible and active in heavily pretreated advanced CRPC patients and seem to support the hypothesis that the addition of EPI to D may lead to overcome the resistance to D in a subgroup of patients.
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Affiliation(s)
- R Petrioli
- Medical Oncology Unit, University of Siena, Viale Bracci 11, 53100, Siena, Italy,
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Rechallenge of docetaxel combined with epirubicin given on a weekly schedule in advanced castration-resistant prostate cancer patients previously exposed to docetaxel and abiraterone acetate: a single-institution experience. MEDICAL ONCOLOGY (NORTHWOOD, LONDON, ENGLAND) 2015. [PMID: 25636506 DOI: 10.1007/s12032-015-0485-232:485] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Subscribe] [Scholar Register] [Indexed: 12/15/2022]
Abstract
The aim of this paper was to evaluate the activity and tolerability of weekly docetaxel (D) combined with weekly epirubicin (EPI) in patients with advanced castrate-resistant prostate cancer (CRPC) previously exposed to D and abiraterone acetate (AA). Locally advanced or metastatic CRPC patients with 0-2 performance status, who had progressed after D and AA therapy, were included in the study. Previous treatment with chemotherapy agent cabazitaxel was also admitted. Treatment consisted of D 30 mg/m(2) intravenously (i.v.) and EPI 30 mg/m(2) i.v., every week (D/EPI). Chemotherapy was administered until disease progression or unacceptable toxicity. In our institution, twenty-six patients received D/EPI: their median age was 72 years (range 59-83 years). Twenty-three (88.5%) patients had bone metastases. A decrease in PSA levels ≥50% was observed in seven patients (26.9%, 95% CI: 0.11-0.47); of these, five had achieved a ≥50% PSA response during prior first-line D and six had achieved a PSA response during prior AA Among the subjects who were symptomatic at baseline, pain was reduced in nine patients (38.1%) with a significant decrease in analgesic use. Median progression-free survival was 4.4 months (95% CI, 3-5.2), and median overall survival was 10.7 months (95% CI, 8.9-18.4). Treatment was well tolerated and no grade 4 toxicities were observed. Our findings suggest that weekly D/EPI is feasible and active in heavily pretreated advanced CRPC patients and seem to support the hypothesis that the addition of EPI to D may lead to overcome the resistance to D in a subgroup of patients.
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