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Azeem M, Ur Rehman A, Rasheed S, Shahzad A, Javed MH, Jamil QA, Karuniawati H, Al-Tamimi SK. The impact of combining cetuximab with the traditional chemotherapy regimens on clinical effectiveness in metastatic colorectal cancer: a systematic review and meta-analysis. BMC Cancer 2025; 25:331. [PMID: 39994602 PMCID: PMC11849154 DOI: 10.1186/s12885-025-13515-3] [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: 08/02/2024] [Accepted: 01/14/2025] [Indexed: 02/26/2025] Open
Abstract
BACKGROUND Metastatic colorectal cancer (mCRC) poses a high rate of morbidity and mortality despite various treatment advances. Cetuximab, an anti-EGFR, has shown promising efficacy in improving outcomes when combined with chemotherapy. Understanding its efficacy is essential for optimizing treatment strategies in mCRC. This systematic review and meta-analysis aims to evaluate the effectiveness of combining cetuximab with chemotherapy in mCRC. METHODS PubMed and Google Scholar were systematically searched following the benchmarks indicated by PRISMA. The primary outcomes of the study were progression-free survival (PFS) and overall survival (OS). Statistical analyses were executed using Stata version 16. RESULTS The meta-analysis encompassed 25 studies involving 3788 mCRC patients. The median age spans from 18 to 77 years. The cetuximab plus chemotherapy exhibited a higher PFS and OS with a significant difference (PFS: HR = 0.79, 95% CI = 0.63-0.96, p < 0.01, I2 = 38% and OS: HR = 0.78, 95% CI = 0.60-0.91, p < 0.01, I2 = 47%) compared to the control group. Subgroup analysis based on randomized controlled trials demonstrated consistent treatment effects for PFS (HR = 0.77, 95% CI = 0.62-0.93) and OS (HR = 0.76, 95% CI = 0.61-0.88) in the cetuximab treatment group. CONCLUSIONS Combining cetuximab with chemotherapy offers a potential benefit in improving survival outcomes for metastatic colorectal cancer patients, as indicated by this study. These results suggest that cetuximab may be a valuable addition to mCRC treatment strategies, warranting further clinical investigation and integration into standard care.
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Affiliation(s)
- Marryam Azeem
- Department of Pharmacy Practice, Faculty of Pharmacy, Bahauddin Zakariya University, Multan, Pakistan
| | - Anees Ur Rehman
- Department of Pharmacy Practice, Faculty of Pharmacy, Bahauddin Zakariya University, Multan, Pakistan.
| | - Saba Rasheed
- Department of Pharmacy Practice, Faculty of Pharmacy, Bahauddin Zakariya University, Multan, Pakistan
| | - Aleena Shahzad
- Department of Pharmacy Practice, Faculty of Pharmacy, Bahauddin Zakariya University, Multan, Pakistan
| | - Muhammad Hamza Javed
- Department of Pharmacy Practice, Faculty of Pharmacy, Bahauddin Zakariya University, Multan, Pakistan
| | - Qurratul Ain Jamil
- Department of Pharmacy Practice, Faculty of Pharmacy, The Islamia University of Bahawalpur, Bahawalpur, Pakistan
| | - Hidayah Karuniawati
- Department of Pharmacology and Clinical Pharmacy, Faculty of Pharmacy, Universitas Muhammadiyah Surakarta, Surakarta, Indonesia
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Han CJ, Ning X, Burd CE, Spakowicz DJ, Tounkara F, Kalady MF, Noonan AM, McCabe S, Von Ah D. Chemotoxicity and Associated Risk Factors in Colorectal Cancer: A Systematic Review and Meta-Analysis. Cancers (Basel) 2024; 16:2597. [PMID: 39061235 PMCID: PMC11274507 DOI: 10.3390/cancers16142597] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/11/2024] [Revised: 07/12/2024] [Accepted: 07/17/2024] [Indexed: 07/28/2024] Open
Abstract
BACKGROUND Colorectal cancer (CRC) patients experience multiple types of chemotoxicity affecting treatment compliance, survival, and quality of life (QOL). Prior research shows clinician-reported chemotoxicity (i.e., grading scales or diagnostic codes) predicts rehospitalization and cancer survival. However, a comprehensive synthesis of clinician-reported chemotoxicity is still lacking. OBJECTIVES We conducted a systematic review and meta-analysis to determine chemotoxicity's prevalence and risk factors in CRC. METHODS A systematic search from 2009 to 2024 yielded 30 studies for review, with 25 included in the meta-analysis. RESULTS Pooled prevalences of overall, non-hematological, and hematological moderate-to-severe toxicities were 45.7%, 39.2%, and 25.3%, respectively. The most common clinician-reported chemotoxicities were gastrointestinal (GI) toxicity (22.9%) and neuropathy or neutropenia (17.9%). Significant risk factors at baseline were malnutritional status, frailty, impaired immune or hepato-renal functions, short telomere lengths, low gut lactobacillus levels, age, female sex, aggressive chemotherapy, and low QOL. Age was associated with neutropenia (β: -1.44) and GI toxicity (β:1.85) (p-values < 0.01). Older adults (>65 y.o.) had higher prevalences of overall (OR: 1.14) and GI (OR: 1.65) toxicities, but a lower prevalence of neutropenia (OR: 0.65) than younger adults (p-values < 0.05). CONCLUSIONS Our findings highlight the importance of closely monitoring and managing chemotoxicity in CRC patients receiving chemotherapy.
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Affiliation(s)
- Claire J. Han
- Center for Healthy Aging, Self-Management and Complex Care, College of Nursing, The Ohio State University, Columbus, OH 43210, USA; (S.M.); (D.V.A.)
- The Ohio State University–James: Cancer Treatment and Research Center, Columbus, OH 43210, USA
| | - Xia Ning
- Clinical Informatics and Implementation Science Biomedical Informatics (BMI), Computer Science and Engineering (CSE), College of Engineering, The Ohio State University, Columbus, OH 43210, USA;
| | - Christin E. Burd
- Departments of Molecular Genetics, Cancer Biology and Genetics, The Ohio State University, Columbus, OH 43210, USA;
| | - Daniel J. Spakowicz
- Pelotonia Institute for Immuno-Oncology, Division of Medical Oncology, The Ohio State University, Comprehensive Cancer Center, Columbus, OH 43210, USA;
| | - Fode Tounkara
- Department of Biomedical Informatics, Ohio State University College of Medicine, Columbus, OH 43210, USA;
| | - Matthew F. Kalady
- Division of Colon and Rectal Surgery, The Ohio State University–James: Cancer Treatment and Research Center, Columbus, OH 43210, USA;
| | - Anne M. Noonan
- GI Medical Oncology Selection, The Ohio State University–James: Cancer Treatment and Research Center, Columbus, OH 43210, USA;
| | - Susan McCabe
- Center for Healthy Aging, Self-Management and Complex Care, College of Nursing, The Ohio State University, Columbus, OH 43210, USA; (S.M.); (D.V.A.)
| | - Diane Von Ah
- Center for Healthy Aging, Self-Management and Complex Care, College of Nursing, The Ohio State University, Columbus, OH 43210, USA; (S.M.); (D.V.A.)
- The Ohio State University–James: Cancer Treatment and Research Center, Columbus, OH 43210, USA
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Soler-González G, Sastre-Valera J, Viana-Alonso A, Aparicio-Urtasun J, García-Escobar I, Gómez-España MA, Guillén-Ponce C, Molina-Garrido MJ, Gironés-Sarrió R. Update on the management of elderly patients with colorectal cancer. Clin Transl Oncol 2024; 26:69-84. [PMID: 37498507 PMCID: PMC10761480 DOI: 10.1007/s12094-023-03243-0] [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: 05/03/2023] [Accepted: 05/31/2023] [Indexed: 07/28/2023]
Abstract
Colorectal cancer (CRC) is one of the most common tumours worldwide, and 70% of CRC patients are over 65 years of age. However, the scientific evidence available for these patients is poor, as they are underrepresented in clinical trials. Therefore, a group of experts from the Oncogeriatrics Section of the Spanish Society of Medical Oncology (SEOM), the Spanish Cooperative Group for the Treatment of Digestive Tumours, (TTD) and the Multidisciplinary Spanish Group of Digestive Cancer (GEMCAD) have reviewed the scientific evidence available in older patients with CRC. This group of experts recommends a multidisciplinary approach and geriatric assessment (GA) before making a therapeutic decision because GA predicts the risk of toxicity and survival and helps to individualize treatment. In addition, elderly patients with localized CRC should undergo standard cancer resection, preferably laparoscopically. The indication for adjuvant chemotherapy (CT) should be considered based on the potential benefit, the risk of recurrence, the life expectancy and patient comorbidities. When the disease is metastatic, the possibility of radical treatment with surgery, radiofrequency (RF) or stereotactic body radiation therapy (SBRT) should be considered. The efficacy of palliative CT is similar to that seen in younger patients, but elderly patients are at increased risk of toxicity. Clinical trials should be conducted with the elderly population and include GAs and specific treatment plans.
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Affiliation(s)
- Gemma Soler-González
- Departamento de Oncología Médica, Spanish Society of Medical Oncology (SEOM) Oncogeriatrics Section, Institut Català d'Oncologia (ICO) L'Hospitalet, Avinguda de la Granvia de l'Hospitalet 199-203, L'Hospitalet de Llobregat, 08908, Barcelona, Spain.
| | - Javier Sastre-Valera
- Spanish Cooperative Group for the Treatment of Digestive Tumours (TTD), Clinico San Carlos University Hospital, Madrid, Spain
| | - Antonio Viana-Alonso
- Spanish Society of Medical Oncology (SEOM) Oncogeriatrics Section, Nuestra Señora del Prado General University Hospital, Talavera de la Reina, Spain
| | - Jorge Aparicio-Urtasun
- Multidisciplinary Spanish Group of Digestive Cancer (GEMCAD), Polytechnic la Fe University Hospital, Valencia, Spain
| | - Ignacio García-Escobar
- Spanish Society of Medical Oncology (SEOM) Oncogeriatrics Section, General University Hospital of Toledo, Toledo, Spain
| | - María Auxiliadora Gómez-España
- Spanish Society of Medical Oncology (SEOM) Oncogeriatrics Section, Reina Sofía University Hospital. Instituto Maimónides de Investigación Biomédica de Córdoba (IMIBIC), Córdoba, Spain
| | - Carmen Guillén-Ponce
- Spanish Society of Medical Oncology (SEOM) Oncogeriatrics Section, Ramón y Cajal University Hospital, Madrid, Spain
| | - María José Molina-Garrido
- Spanish Society of Medical Oncology (SEOM) Oncogeriatrics Section, Virgen de la Luz Hospital, Cuenca, Spain
| | - Regina Gironés-Sarrió
- Spanish Society of Medical Oncology (SEOM) Oncogeriatrics Section, Polytechnic la Fe University Hospital, Valencia, Spain
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Jiang H, Zhou S, Li G. Novel biomarkers used for early diagnosis and tyrosine kinase inhibitors as targeted therapies in colorectal cancer. Front Pharmacol 2023; 14:1189799. [PMID: 37719843 PMCID: PMC10502318 DOI: 10.3389/fphar.2023.1189799] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/20/2023] [Accepted: 08/14/2023] [Indexed: 09/19/2023] Open
Abstract
Colorectal cancer (CRC) is the third most common and second most lethal type of cancer worldwide, presenting major health risks as well as economic costs to both people and society. CRC survival chances are significantly higher if the cancer is diagnosed and treated early. With the development of molecular biology, numerous initiatives have been undertaken to identify novel biomarkers for the early diagnosis of CRC. Pathological disorders can be diagnosed at a lower cost with the help of biomarkers, which can be detected in stool, blood, and tissue samples. Several lines of evidence suggest that the gut microbiota could be used as a biomarker for CRC screening and treatment. CRC treatment choices include surgical resection, chemotherapy, immunotherapy, gene therapy, and combination therapies. Targeted therapies are a relatively new and promising modality of treatment that has been shown to increase patients' overall survival (OS) rates and can inhibit cancer cell development. Several small-molecule tyrosine kinase inhibitors (TKIs) are being investigated as potential treatments due to our increasing awareness of CRC's molecular causes and oncogenic signaling. These compounds may inhibit critical enzymes in controlling signaling pathways, which are crucial for CRC cells' development, differentiation, proliferation, and survival. On the other hand, only one of the approximately 42 TKIs that demonstrated anti-tumor effects in pre-clinical studies has been licensed for clinical usage in CRC. A significant knowledge gap exists when bringing these tailored medicines into the clinic. As a result, the emphasis of this review is placed on recently discovered biomarkers for early diagnosis as well as tyrosine kinase inhibitors as possible therapy options for CRC.
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Rosati G, Montrone M, Pacilio C, Colombo A, Cicero G, Paragliola F, Vaia A, Annunziata L, Bilancia D. An Update on the Role of Anti-EGFR in the Treatment of Older Patients with Metastatic Colorectal Cancer. J Clin Med 2022; 11:jcm11237108. [PMID: 36498683 PMCID: PMC9739901 DOI: 10.3390/jcm11237108] [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: 10/01/2022] [Revised: 11/10/2022] [Accepted: 11/27/2022] [Indexed: 12/02/2022] Open
Abstract
Although colorectal cancer is increasingly being diagnosed in older patients, their number is largely underrepresented in phase II or III clinical trials. Consequently, guidelines and the SIOG recommendations are not sufficiently clear regarding the treatment of these patients, particularly when chemotherapy is combined with monoclonal antibodies (bevacizumab, cetuximab, and panitumumab). Targeted therapy based on the use of anti-epidermal growth factor receptors (EGFRs) is conditioned by the potential for increased toxicity, making it more difficult to treat an older, rat sarcoma virus (RAS) and B rapidly accelerated fibrosarcoma (BRAF) wild-type patient. In light of a more detailed characterization of the older population, modernly differentiable between fit, vulnerable, or frail patients on the basis of the comprehensive geriatric assessment, and of the analysis of more recent studies, this review fully collects data from the literature, differentiating the results on functional status patients.
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Affiliation(s)
- Gerardo Rosati
- Medical Oncology Unit, “San Carlo” Hospital, 85100 Potenza, Italy
- Correspondence: ; Tel.: +39-0971-612273
| | - Michele Montrone
- Medical Thoracic Oncology Unit, IRCCS Istituto Tumori “Giovanni Paolo II”, 70124 Bari, Italy
| | - Carmen Pacilio
- Medical Breast Cancer Department, IRCCS Istituto Tumori “G. Pascale”, 80131 Napoli, Italy
| | - Alfredo Colombo
- Medical Oncology Unit, CDC Macchiarella, 90138 Palermo, Italy
| | - Giuseppe Cicero
- Medical Oncology, Università degli Studi di Palermo, 90133 Palermo, Italy
| | | | - Angelo Vaia
- Medical Oncology Unit, “San Carlo” Hospital, 85100 Potenza, Italy
| | - Luigi Annunziata
- Medical Oncology Unit, “San Carlo” Hospital, 85100 Potenza, Italy
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Jang HR, Lee HY, Song SY, Lim KH. Clinical outcomes of targeted therapies in elderly patients aged ≥ 80 years with metastatic colorectal cancer. World J Clin Cases 2022; 10:10066-10076. [PMID: 36246797 PMCID: PMC9561573 DOI: 10.12998/wjcc.v10.i28.10066] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/07/2022] [Revised: 07/26/2022] [Accepted: 08/17/2022] [Indexed: 02/05/2023] Open
Abstract
BACKGROUND The 5-fluorouracil-based chemotherapy combined with oxaliplatin or irinotecan is usually used in colorectal cancer (CRC). The addition of a targeted agent (TA) to this combination chemotherapy is currently the standard treatment for metastatic CRC. However, the efficacy and safety of combination chemotherapy for metastatic CRC in patients aged above 80 years has yet to be established.
AIM To assess the clinical outcomes and feasibility of combination chemotherapy using a TA in extremely elderly patients with CRC.
METHODS Eligibility criteria were: (1) Age above 80 years; (2) Metastatic colorectal cancer; (3) Palliative chemotherapy naïve; (4) Eastern Cooperative Oncology Group performance status 0-1; and (5) Adequate organ function. Patients received at least one dose of combination chemotherapy with or without TA. Response was evaluated every 8 wk.
RESULTS Of 30 patients, the median age of 15 patients treated with TA was 83.0 years and that of those without TA was 81.3 years. The median progression-free survival (PFS) and overall survival (OS) in patients treated with TA were 7.4 mo and 15.4 mo, respectively, compared with 4.4 mo and 15.6 mo, respectively, in patients treated without TA. There was no significant difference in PFS (P: 0.193) and OS (P: 0.748) between patients treated with and without TA. Common grade 3/4 hematologic toxicities were anemia (16.7%) and neutropenia (10.0%). After disease progression, the median OS of patients who were treated with and without salvage chemotherapy were 23.5 mo and 7.0 mo, respectively, suggesting significant difference in OS (P = 0.001).
CONCLUSION Combination chemotherapy with TA for metastatic CRC may be considered feasible in patients aged above 80 years, when with careful caution. Salvage chemotherapy can help improve OS in some selected of these elderly patients.
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Affiliation(s)
- Hee Ryeong Jang
- Department of Internal Medicine, Kangwon National University Hospital, Kangwon National University School of Medicine, Chuncheon-si, Gangwon-do 24289, South Korea
| | - Hui-Young Lee
- Department of Internal Medicine, Kangwon National University Hospital, Kangwon National University School of Medicine, Chuncheon-si, Gangwon-do 24289, South Korea
| | - Seo-Young Song
- Department of Internal Medicine, Kangwon National University Hospital, Kangwon National University School of Medicine, Chuncheon-si, Gangwon-do 24289, South Korea
| | - Kyu-Hyoung Lim
- Department of Internal Medicine, Kangwon National University Hospital, Kangwon National University School of Medicine, Chuncheon-si, Gangwon-do 24289, South Korea
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Efficacy of FOLFIRI plus cetuximab vs FOLFIRI plus bevacizumab in 1st-line treatment of older patients with RAS wild-type metastatic colorectal cancer: an analysis of the randomised trial FIRE-3. Br J Cancer 2022; 127:836-843. [PMID: 35637412 PMCID: PMC9427779 DOI: 10.1038/s41416-022-01854-y] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/26/2021] [Revised: 04/14/2022] [Accepted: 05/09/2022] [Indexed: 12/09/2022] Open
Abstract
Summary
Background
The evidence on the efficacy of anticancer therapy is limited in older patients with metastatic colorectal cancer (mCRC). This retrospective analysis of phase III FIRE-3 trial assesses the efficacy of FOLFIRI plus either cetuximab or bevacizumab according to the patients’ age and sidedness of primary tumour.
Methods
The study endpoints overall response rate (ORR), progression-free survival (PFS) and overall survival (OS) were compared between younger (<65 years) and older (≥65 years) patients, followed by stratification according to primary tumour sidedness. ORR was compared using Fisher´s exact test, OS and PFS were estimated by the Kaplan–Meier method and compared using the log-rank test. Univariate Cox regression analyses assessed hazard ratios and 95% confidence intervals for OS and PFS.
Results
Overall, older patients with RAS WT tumours had a significantly shorter OS when compared to younger patients (25.9 months vs 29.3 months, HR 1.29; P = 0.02). Also the proportion of right-sided tumours was significantly greater in older patients (27.1% vs 17.9%; P = 0.029). Secondary resection rates were numerically higher in younger patients (25.4% vs. 17.6%, P = 0.068) than in older patients. This was primarily seen in the Cetuximab arm, where older patients underwent less likely resection (13.1% vs. 26%; P = 0.02). Older patients with left-sided tumours showed only a trend towards greater efficacy of cetuximab (HR 0.86; P = 0.38). In patients with right-sided primary tumours, older patients did not appear to benefit from cetuximab in contrast to younger patients (≥65 years: 16.6 months vs 23.6 months, HR 1.1; P = 0.87; <65 years: 21.9 months vs 16.4 months HR 1.5; P = 0.31).
Conclusions
In FIRE-3, OS was generally shorter in older patients in comparison to younger patients. This could be explained by the overrepresentation of right-sided tumours and a lower secondary resection rate in older patients. The efficacy of targeted therapy was dependent on tumour sidedness in older patients with RAS WT mCRC.
Clinical trial
FIRE-3 (NCT00433927).
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McCleary NJ, Harmsen WS, Haakenstad E, Cleary JM, Meyerhardt JA, Zalcberg J, Adams R, Grothey A, Sobrero AF, Van Cutsem E, Goldberg RM, Peeters M, Tabernero J, Seymour M, Saltz LB, Giantonio BJ, Arnold D, Rothenberg ML, Koopman M, Schmoll HJ, Pitot HC, Hoff PM, Tebbutt N, Masi G, Souglakos J, Bokemeyer C, Heinemann V, Yoshino T, Chibaudel B, deGramont A, Shi Q, Lichtman SM. Metastatic Colorectal Cancer Outcomes by Age Among ARCAD First- and Second-Line Clinical Trials. JNCI Cancer Spectr 2022; 6:pkac014. [PMID: 35603849 PMCID: PMC8935011 DOI: 10.1093/jncics/pkac014] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/28/2021] [Revised: 09/09/2021] [Accepted: 11/04/2021] [Indexed: 12/14/2022] Open
Abstract
BACKGROUND We evaluated the time to progression (TTP) and survival outcomes of second-line therapy for metastatic colorectal cancer among adults aged 70 years and older compared with younger adults following progression on first-line clinical trials. METHODS Associations between clinical and disease characteristics, time to initial progression, and rate of receipt of second-line therapy were evaluated. TTP and overall survival (OS) were compared between older and younger adults in first- and second-line trials by Cox regression, adjusting for age, sex, Eastern Cooperative Oncology Group Performance Status, number of metastatic sites and presence of metastasis in the lung, liver, or peritoneum. All statistical tests were 2-sided. RESULTS Older adults comprised 16.4% of patients on first-line trials (870 total older adults aged >70 years; 4419 total younger adults aged ≤70 years, on first-line trials). Older adults and those with Eastern Cooperative Oncology Group Performance Status >0 were less likely to receive second-line therapy than younger adults. Odds of receiving second-line therapy decreased by 11% for each additional decade of life in multivariable analysis (odds ratio = 1.11, 95% confidence interval = 1.02 to 1.21, P = .01). Older and younger adults enrolled in second-line trials experienced similar median TTP and median OS (median TTP = 5.1 vs 5.2 months, respectively; median OS = 11.6 vs 12.4 months, respectively). CONCLUSIONS Older adults were less likely to receive second-line therapy for metastatic colorectal cancer, though we did not observe a statistical difference in survival outcomes vs younger adults following second-line therapy. Further study should examine factors affecting decisions to treat older adults with second-line therapy. Inclusion of geriatric assessment may provide better criteria regarding the risks and benefits of second-line therapy.
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Affiliation(s)
- Nadine J McCleary
- Gastrointestinal Cancer Center, Dana-Farber Cancer Institute, Boston, MA, USA
| | - William S Harmsen
- Department of Health Science Research, Mayo Clinic, Rochester, MN, USA
| | - Ellana Haakenstad
- Gastrointestinal Cancer Center, Dana-Farber Cancer Institute, Boston, MA, USA
| | - James M Cleary
- Gastrointestinal Cancer Center, Dana-Farber Cancer Institute, Boston, MA, USA
| | | | | | - Richard Adams
- Cardiff University and Velindre Cancer Centre, Cardiff, UK
| | - Axel Grothey
- West Cancer Center and Research Institute, OneOncology, Germantown, TN, USA
| | | | | | - Richard M Goldberg
- West Virginia University Cancer Institute and the Mary Babb Randolph Cancer Center, Morgantown, WV, USA
| | - Marc Peeters
- Department of Oncology, Antwerp University Hospital, Antwerp, Belgium
| | - Josep Tabernero
- Vall d’Hebron University Hospital and Institute of Oncology (VHIO), Institute of Oncology Barcelona-Quiron, UVic-UCC, Barcelona, Spain
| | - Matt Seymour
- NIHR Clinical Research Network, Leeds, UK
- St. James’s Hospital and University of Leeds, Leeds, UK
| | | | - Bruce J Giantonio
- Perelman School of Medicine Abramson Cancer Center, University of Pennsylvania, Philadelphia, PA, USA
| | - Dirk Arnold
- Instituto CUF de Oncologia, Lisbon, Portugal
- Asklepios Tumorzentrum Hamburg, Asklepios Klinik Altona, Hamburg, Germany
| | | | - Miriam Koopman
- Department of Medical Oncology, University Medical Center Utrecht, University of Urtrecht, Utrecht, Netherlands
| | - Hans-Joachim Schmoll
- Klinik fur Innere Med IV, University Clinic Halle (Saale), Halle, Germany
- Martin Luther University, Halle, Germany
| | - Henry C Pitot
- Department of Oncology, Mayo Clinic, Rochester, MN, USA
| | - Paulo M Hoff
- Centro de Oncologia de Brasilia do Sirio Libanes-Unidade Lago Sul, Siro Libanes, Brazil
- Universidade de São Paulo Instituto do Cancer do Estado de São Paulo, São Paulo, Brazil
| | - Niall Tebbutt
- University of Sydney Medical School, Sydney, Australia
- Austin Health, Heidelberg, Victoria, Australia
| | - Gianluca Masi
- Department of Oncology, University of Pisa, Pisa, Italy
| | - John Souglakos
- Department of Medical Oncology, University General Hospital of Heraklion, Heraklion, Greece
| | | | - Volker Heinemann
- Department of Hematology/Oncology, Comprehensive Cancer Center Munich, University Hospital, LMU Munich, Germany
| | | | - Benoist Chibaudel
- Department of Medical Oncology, Institut Franco-Britannique, Levallois-Perret, France
| | - Aimery deGramont
- Department of Medical Oncology, Institut Franco-Britannique, Levallois-Perret, France
| | - Qian Shi
- Department of Health Science Research, Mayo Clinic, Rochester, MN, USA
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Reduced-dose of doublet chemotherapy combined with anti-EGFR antibodies in vulnerable older patients with metastatic colorectal cancer: Data from the REVOLT study. J Geriatr Oncol 2021; 13:302-307. [PMID: 34716122 DOI: 10.1016/j.jgo.2021.10.007] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/29/2021] [Revised: 10/12/2021] [Accepted: 10/18/2021] [Indexed: 11/21/2022]
Abstract
OBJECTIVES To assess the toxicity patterns and effectiveness of doublet chemotherapy when administered at reduced doses of 20% (FOLFOX or FOLFIRI) in combination with anti-EGFR antibodies (cetuximab or panitumumab) in old, vulnerable patients with metastatic colorectal cancer (mCRC). PATIENTS AND METHODS We performed a retrospective observational study of RAS and BRAF wild-type, vulnerable patients aged ≥70 years with previously untreated mCRC. The primary endpoint was safety, and secondary endpoints were overall response rate (ORR), progression-free survival (PFS), and overall survival (OS). RESULTS One hundred and eighteen patients were collected from 14 selected Italian centres. The median age was 75 (range, 70-85). Geriatric screening by G8 tool gave a score ≤ 14 in all patients. In total, 75 and 43 patients received FOLFOX or FOLFIRI, respectively, in combination with panitumumab (53%) or cetuximab (47%). The overall incidence of grade (G) 3-4 neutropenia was 11.8%, and for skin rash 11%. The most frequent adverse events were G1-2 skin rash (49.1%), G1-2 diarrhea (21.1%) and G1-2 nausea (17.7%). The ORR was 57.3%. Stable disease was observed in 29.1% of patients, with a disease control rate of 86.4%. With a median follow-up of 18 months, the median PFS was 10.0 months (95% confidence interval [CI]: 8.5-11.4), while the median OS was 18.0 months (95% CI: 16.0-19.9). No statistically significant difference was observed between the regimens in terms of ORR, PFS (p = 0.908), and OS (p = 0.832). CONCLUSION This study shows that with an appropriate design, including reduced doses, vulnerable older patients best tolerate chemotherapy when combined with anti-EGFR antibodies.
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Capecitabine in combination with panitumumab is not the treatment of choice in older patients with metastatic colorectal cancer. J Geriatr Oncol 2021; 13:114-115. [PMID: 34507891 DOI: 10.1016/j.jgo.2021.09.001] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/09/2020] [Accepted: 09/01/2021] [Indexed: 11/23/2022]
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Siu HWD, Tebbutt N, Chantrill L, Karapetis C, Steer C, Wilson K, Espinoza D, Bailey L, Yip S, Cuff J, Pavlakis N, Thavaneswaran S, Briscoe K, Srivastav R, Shannon J, Segelov E, Tie J, Caird S, Francesconi A, Price T, Wuttke M, Ladwa R, Sjoquist K, Burge M. MONARCC: a randomised phase II study of panitumumab monotherapy and panitumumab plus 5-fluorouracil as first-line therapy for RAS and BRAF wildtype metastatic colorectal cancer: a study by the Australasian Gastrointestinal Trials Group (AGITG). BMC Cancer 2021; 21:932. [PMID: 34407800 PMCID: PMC8371602 DOI: 10.1186/s12885-021-08644-4] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/21/2020] [Accepted: 07/19/2021] [Indexed: 12/22/2022] Open
Abstract
Background Doublet chemotherapy in combination with a biologic agent has been a standard of care in patients with metastatic colorectal cancer for over a decade. The evidence for a “lighter” treatment approach is limited to mono-chemotherapy plus bevacizumab in the RAS unselected population. Anti-EGFR antibodies have activity as monotherapy or in combination with chemotherapy in RAS wildtype metastatic colorectal cancer; however their role in first-line treatment in combination with 5-fluorouracil monotherapy or when given alone has not been well studied. MONARCC aims to investigate this approach in an elderly population. Methods/design MONARCC is a prospective, open-label, multicentre, non-comparative randomised phase II trial. Eligible patients aged ≥70 with unresectable metastatic, untreated, RAS/BRAF wildtype metastatic colorectal cancer will be randomised 1:1 to receive panitumumab alone or panitumumab plus infusional 5-fluorouracil. RAS and BRAF analyses will be performed in local laboratories. Comprehensive Health Assessment and Limited Health Assessments will be performed at baseline and at 16 weeks, respectively, to assess frailty. The Patient Symptom Questionnaire and Overall Treatment Utility are to be undertaken at different timepoints to assess the impact of treatment-related toxicities and quality of life. Treatment will be delivered every 2 weeks until disease progression, unacceptable toxicity (as determined by treating clinician or patient), delay of treatment of more than 6 weeks, or withdrawal of consent. The primary end point is 6-month progression-free survival in both arms. Secondary end points include overall survival, time to treatment failure, objective tumour response rate as defined by RECIST v1.1 and safety (adverse events). Tertiary and correlative endpoints include the feasibility and utility of a comprehensive geriatric assessment, quality of life and biological substudies. Discussion MONARCC investigates the activity and tolerability of first-line panitumumab-based treatments with a view to expand on current treatment options while maximising progression-free and overall survival and quality of life in molecularly selected elderly patients with metastatic colorectal cancer. Trial registration Australia New Zealand Clinical Trials Registry: ACTRN12618000233224, prospectively registered 14 February 2018. Supplementary Information The online version contains supplementary material available at 10.1186/s12885-021-08644-4.
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Affiliation(s)
- Ho Wai Derrick Siu
- NHMRC Clinical Trials Centre, University of Sydney, Sydney, Australia. .,, Camperdown, Australia.
| | | | | | | | | | - Kate Wilson
- NHMRC Clinical Trials Centre, University of Sydney, Sydney, Australia
| | - David Espinoza
- NHMRC Clinical Trials Centre, University of Sydney, Sydney, Australia
| | - Lisa Bailey
- NHMRC Clinical Trials Centre, University of Sydney, Sydney, Australia
| | - Sonia Yip
- NHMRC Clinical Trials Centre, University of Sydney, Sydney, Australia
| | - Jeff Cuff
- Australasian Gastrointestinal Group (AGITG), Sydney, Australia
| | | | | | - Karen Briscoe
- Coffs Harbour Health Campus, Coffs Harbour, Australia
| | | | | | | | | | - Susan Caird
- Gold Coast University Hospital, Gold Coast, Australia
| | | | | | | | - Rahul Ladwa
- Princess Alexandra Hospital, Brisbane, Australia
| | - Katrin Sjoquist
- NHMRC Clinical Trials Centre, University of Sydney, Sydney, Australia
| | - Matthew Burge
- Royal Brisbane and Women's Hospital, Brisbane, Australia.,The Prince Charles Hospital, Brisbane, Australia
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12
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Correa E, Lindsay T, Dotan E. Management of Metastatic Colorectal Carcinoma in Older Adults: Balancing Risks and Benefits of Novel Therapies. Drugs Aging 2021; 38:639-654. [PMID: 34143421 PMCID: PMC9951235 DOI: 10.1007/s40266-021-00869-z] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 05/22/2021] [Indexed: 11/25/2022]
Abstract
The prevalence of older patients with metastatic colorectal cancer (mCRC) will continue to increase with our aging population. Treatment of mCRC has changed significantly in the last few decades as we have learned how to personalize the treatment of mCRC to the biology of the tumor, utilizing new treatment approaches. With an ever-changing treatment paradigm, managing the population of older adults becomes paramount. This review highlights the pivotal clinical trials that defined the use of systemic therapy, immunotherapy and targeted therapies for mCRC, and how those are applied to the older patient population. In addition, we outline the tools for an in-depth assessment of an older adult in regards to treatment planning and management of therapy-related toxicities. A comprehensive geriatric assessment can assist in the selection of treatment for an older adult with mCRC. While frail older patients can frequently only tolerate single agents or modified regimens, fit older adults remain candidates for a wider range of treatment options. However, since all of these treatments are associated with possible toxicities, each patient's treatment must be personalized to the patient's goals and wishes through a shared decision-making process.
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Affiliation(s)
- Erika Correa
- Department of Hematology/Oncology, Fox Chase Cancer Center, Philadelphia, PA, USA
| | - Timothy Lindsay
- Department of Hematology/Oncology, Fox Chase Cancer Center, Philadelphia, PA, USA
| | - Efrat Dotan
- Department of Hematology/Oncology, Fox Chase Cancer Center, Philadelphia, PA, USA.
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13
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Monteiro AR, Conde RS, Basto R, Sclafani F, Deleporte A, Hendlisz A, Dal Lago L. Targeted agents in older patients with gastrointestinal cancers - An overview. J Geriatr Oncol 2021; 12:1240-1252. [PMID: 34226158 DOI: 10.1016/j.jgo.2021.06.013] [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: 04/07/2021] [Revised: 06/12/2021] [Accepted: 06/25/2021] [Indexed: 12/24/2022]
Abstract
Targeted agents have been increasingly used in different malignancies and are associated with improved survival outcomes, including gastrointestinal cancers. Their use in the treatment of older patients is appealing given their favorable toxicity profile. In the last years, this subgroup of patients has been attracting increased interest given their representativeness and specific clinical needs. Nonetheless, the lack of data on efficacy and safety of standard treatments in older patients hinders proper evidence-based decision-making, leaving most therapeutic recommendations to be extrapolated from registration trials with low representation of older and frail patients. However, even if most decisions regarding the use of targeted agents in older patients with gastrointestinal cancer remain guided by subanalyses of large trials, data from recent older adult-specific trials are beginning to emerge, particularly in colorectal cancer. This review aims to summarize the existing evidence on treatment of older patients with gastrointestinal carcinomas (colon and rectum, stomach, esophagus, liver, and pancreas) with targeted agents (cetuximab, panitumumab, bevacizumab, ramucirumab, aflibercept, regorafenib, encorafenib, trastuzumab, sorafenib, lenvatinib, cabozantinib, erlotinib, olaparib), and place the evidence in a geriatric oncology perspective.
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Affiliation(s)
- Ana Raquel Monteiro
- Instituto Português de Oncologia de Coimbra Francisco Gentil, Department of Medical Oncology, Av. Bissaya Barreto 98, 3000-075 Coimbra, Portugal.
| | - Rita Saúde Conde
- Instituto Português de Oncologia de Lisboa Francisco Gentil, Department of Medical Oncology, Rua Professor Lima Basto, 1099-023 Lisboa, Portugal.
| | - Raquel Basto
- Instituto Português de Oncologia de Coimbra Francisco Gentil, Department of Medical Oncology, Av. Bissaya Barreto 98, 3000-075 Coimbra, Portugal.
| | - Francesco Sclafani
- Institut Jules Bordet, Department of Medicine, Blvd de Waterloo 121, 1000 Brussels, Belgium.
| | - Amélie Deleporte
- Institut Jules Bordet, Department of Medicine, Blvd de Waterloo 121, 1000 Brussels, Belgium.
| | - Alain Hendlisz
- Institut Jules Bordet, Department of Medicine, Blvd de Waterloo 121, 1000 Brussels, Belgium.
| | - Lissandra Dal Lago
- Institut Jules Bordet, Department of Medicine, Blvd de Waterloo 121, 1000 Brussels, Belgium.
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14
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García-Alfonso P, Muñoz Martín AJ, Ortega Morán L, Soto Alsar J, Torres Pérez-Solero G, Blanco Codesido M, Calvo Ferrandiz PA, Grasso Cicala S. Oral drugs in the treatment of metastatic colorectal cancer. Ther Adv Med Oncol 2021; 13:17588359211009001. [PMID: 33995592 PMCID: PMC8111515 DOI: 10.1177/17588359211009001] [Citation(s) in RCA: 31] [Impact Index Per Article: 7.8] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/10/2020] [Accepted: 03/17/2021] [Indexed: 12/18/2022] Open
Abstract
Colorectal cancer (CRC) is one of the most common forms of cancer, with an estimated 1.36 million new cases and almost 700,000 deaths annually. Approximately 21% of patients with CRC have metastatic disease at diagnosis. The objective of this article is to review the literature on the efficacy and safety of oral drugs available for the treatment of metastatic colorectal cancer (mCRC). Several such drugs have been developed, and fluoropyrimidines are the backbone of chemotherapy in this indication. They exert their antitumour activity by disrupting the synthesis and function of DNA and RNA. Oral fluoropyrimidines include prodrugs capecitabine, tegafur, eniluracil/5-fluorouracil, tegafur/uracil, tegafur/gimeracil/oteracil and trifluridine/tipiracil (FTD/TPI). Oral drugs offer several advantages over injectable formulations, including convenience, flexibility, avoidance of injection-related adverse events (AEs) and, in some circumstances, lower costs. However, oral drugs may not be suitable for patients with gastrointestinal obstruction or malabsorption, they may result in reduced treatment adherence and should not be co-administered with drugs that interfere with absorption or hepatic metabolism. Oral fluoropyrimidines such as capecitabine, as monotherapy or in combination with oxaliplatin, irinotecan or bevacizumab, are as effective as intravenous 5-fluorouracil (5-FU) in first-line treatment of mCRC. Other oral fluoropyrimidines, such as FTD/TPI, are effective in patients with mCRC who are refractory, intolerant or ineligible for 5-FU. In addition, oral fluoropyrimidines are used in adjuvant treatment of mCRC. Regorafenib is an oral multikinase inhibitor used in patients in whom several previous lines of therapy have failed. Frequent AEs associated with oral drugs used in the treatment of CRC include hand-foot syndrome and gastrointestinal and haematological toxicities.
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Affiliation(s)
- Pilar García-Alfonso
- Oncología Médica, Hospital General Universitario Gregorio Marañón, Calle Doctor Esquerdo 46, Madrid, 28009, Spain
| | | | - Laura Ortega Morán
- Oncología Médica, Hospital General Universitario Gregorio Marañón, Madrid, Spain
| | - Javier Soto Alsar
- Oncología Médica, Hospital General Universitario Gregorio Marañón, Madrid, Spain
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Niedersüß-Beke D, Orlinger M, Falch D, Heiler C, Piringer G, Thaler J, Hilbe W, Petzer A, Rumpold H. Clinical Effectiveness of Oncological Treatment in Metastatic Colorectal Cancer Is Independent of Comorbidities and Age. Cancers (Basel) 2021; 13:cancers13092091. [PMID: 33925931 PMCID: PMC8123394 DOI: 10.3390/cancers13092091] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/05/2021] [Revised: 04/20/2021] [Accepted: 04/22/2021] [Indexed: 12/14/2022] Open
Abstract
Simple Summary Colorectal cancer (CRC) is the third most common cancer worldwide. As with many other cancers, the risk for CRC increases with age. This is also true for comorbidities, which may hamper sufficient treatment of the cancer. Due to restrictive inclusion criteria, older patients and patients with comorbidities are underrepresented in clinical trials. Comprehensive knowledge about modern effectiveness of oncological treatments in older and/or comorbid patients is sparse. Due to the lack of clinical trials, this issue is investigated in real-life settings predominantly. In our retrospective study we show that patients benefit from oncological treatments irrespective of comorbidities, measured by the age-adjusted Charlson Comorbity (aaCCI) index, and age. Differences found in treatment outcomes are marginal and are likely due to less intense treatment of comorbid or elderly patients. Balancing risk and benefit for treatment decisions should take potential under-treatment of comorbid and older patients into account. Abstract We aimed to investigate the effectiveness of oncological treatments in metastatic CRC related to comorbidities and age. This retrospective study included 1105 patients from three oncological centers. aaCCI and CCI was available from 577 patients. An aaCCI > 3 was of the highest predictive value compared to other aaCCI-levels, CCI or age (p < 0.001 for all). Treatment (best supportive care (BSC), systemic treatment only (STO) and resection of metastases (ROM)) significantly prolonged survival in patients with aaCCI > 3 (STO: HR 0.39, CI 0.29–0.51; ROM: HR 0.16, CI 0.10–0.24) and patients older than 70 years (STO: HR 0.56, CI 0.47–0.66; ROM: HR 0.23, 0.18–0.30). Median overall survival was shorter in patients with aaCCI or age > 70 years and interaction for treatment type not significant for aaCCI, but significant for age older or younger than 70 years (STO: p = 0.01; ROM p = 0.02). BSC is more often considered as optimal care for patients with an aaCCI > 3 (37.6% vs. 12.4%; p < 0.001) or age > 70 years (35.7% vs. 11.2%; p < 0.001). Older patients or patients with comorbidities benefit from cancer-specific therapy independently of their age and comorbidities.
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Affiliation(s)
- Dora Niedersüß-Beke
- Department of Internal Medicine I, Wilhelminenspital, 1160 Vienna, Austria; (D.N.-B.); (D.F.); (C.H.); (W.H.)
| | - Manuel Orlinger
- Department of Hematology and Medical Oncology, Ordensklinikum Linz, 4010 Linz, Austria; (M.O.); (A.P.)
| | - David Falch
- Department of Internal Medicine I, Wilhelminenspital, 1160 Vienna, Austria; (D.N.-B.); (D.F.); (C.H.); (W.H.)
| | - Cordula Heiler
- Department of Internal Medicine I, Wilhelminenspital, 1160 Vienna, Austria; (D.N.-B.); (D.F.); (C.H.); (W.H.)
| | - Gudrun Piringer
- Department of Internal Medicine IV, Hospital Wels-Grieskirchen, 4600 Wels, Austria; (G.P.); (J.T.)
- Medical Faculty, Johannes Kepler University Linz, 4020 Linz, Austria
| | - Josef Thaler
- Department of Internal Medicine IV, Hospital Wels-Grieskirchen, 4600 Wels, Austria; (G.P.); (J.T.)
| | - Wolfgang Hilbe
- Department of Internal Medicine I, Wilhelminenspital, 1160 Vienna, Austria; (D.N.-B.); (D.F.); (C.H.); (W.H.)
| | - Andreas Petzer
- Department of Hematology and Medical Oncology, Ordensklinikum Linz, 4010 Linz, Austria; (M.O.); (A.P.)
| | - Holger Rumpold
- Medical Faculty, Johannes Kepler University Linz, 4020 Linz, Austria
- Gastrointestinal Cancer Center, Ordensklinikum Linz, 4010 Linz, Austria
- Correspondence:
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16
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Tuca A, Gallego R, Ghanem I, Gil-Raga M, Feliu J. Chemotherapy and Targeted Agents in the Treatment of Elderly Patients with Metastatic Colorectal Cancer. J Clin Med 2020; 9:E4015. [PMID: 33322567 PMCID: PMC7764481 DOI: 10.3390/jcm9124015] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/10/2020] [Revised: 12/04/2020] [Accepted: 12/07/2020] [Indexed: 12/20/2022] Open
Abstract
Colorectal cancer (CRC) is one of the main causes of cancer death in the elderly. The older patients constitute a heterogeneous group in terms of functional status, comorbidities, and aging-related conditions. Therefore, therapeutic decisions need to be individualized. Additionally, a higher toxicity risk comes from the fact that pharmacokinetics and pharmacodynamics of the drugs as well as the tissue tolerance can be altered with aging. Although the chemotherapy efficacy in metastatic colorectal cancer (mCRC) is similar for older and young patients, more toxicity is presented in the elderly. While the mono-chemotherapy provides the same benefit for young and older patients, doublets front-line chemotherapy improves progression-free survival (PFS) but not overall survival (OS) in the elderly. Furthermore, the benefit of the addition of bevacizumab to chemotherapy in older patients has been shown in several clinical trials, while the clinical data for the benefit of anti-epidermal growth factor antibodies are scarcer. Immunocheckpoint inhibitors could be an appropriate option for patients with microsatellite instability (MSI) tumors. A prior geriatric assessment is required before deciding the type of treatment in order to offer the best therapeutic option.
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Affiliation(s)
- Albert Tuca
- Department of Medical Oncology, Hospital Clinic, 08036 Barcelona, Spain;
| | - Rosa Gallego
- Department of Medical Oncology, General Hospital of Granollers, 08402 Granollers, Spain;
| | - Ismael Ghanem
- Department of Medical Oncology, Hospital Universitario La Paz, CIBERONC, 28046 Madrid, Spain;
| | - Mireia Gil-Raga
- Department of Medical Oncology, University General Hospital of Valencia, CIBERONC, 46014 Valencia, Spain;
| | - Jaime Feliu
- Department of Medical Oncology, Hospital Universitario La Paz, CIBERONC, 28046 Madrid, Spain;
- Cátedra UAM-AMGEN, 28049 Madrid, Spain
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17
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Méndez Méndez JC, Salgado Fernández M, de la Cámara Gómez J, Pellón Augusto ML, Covela Rua M, Quintero Aldana G, Fernández Montes A, Reboredo López M, Valladares Ayerbes M, Jorge Fernández M, González Villarroel P, Romero Reinoso C, Ramos Vázquez M. First-line panitumumab plus capecitabine for the treatment of older patients with wild-type RAS metastatic colorectal cancer. The phase II, PANEL study. J Geriatr Oncol 2020; 11:1263-1267. [DOI: 10.1016/j.jgo.2020.06.003] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/11/2020] [Revised: 04/24/2020] [Accepted: 06/03/2020] [Indexed: 12/12/2022]
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Gilabert M, Ries P, Chanez B, Triby S, Francois E, Lièvre A, Rousseau F. Place of anti-EGFR therapy in older patients with metastatic colorectal cancer in 2020. J Geriatr Oncol 2020; 11:1229-1236. [DOI: 10.1016/j.jgo.2020.04.004] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/03/2020] [Revised: 03/02/2020] [Accepted: 04/15/2020] [Indexed: 12/24/2022]
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Battisti NML, Liposits G, De Glas NA, Gomes F, Baldini C, Mohile S. Systemic Therapy of Common Tumours in Older Patients: Challenges and Opportunities. A Young International Society of Geriatric Oncology Review Paper. Curr Oncol Rep 2020; 22:98. [PMID: 32725503 DOI: 10.1007/s11912-020-00958-z] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/08/2023]
Abstract
PURPOSE OF REVIEW Decision-making for systemic treatments in older patients with cancer is difficult because of concerns for decreased organ function, risk of toxicity, limited life expectancy due to comorbidities and the lack of evidence available to guide its management in this population. Here, we review the data on the role of systemic agents for the treatment of common malignancies in this age group. RECENT FINDINGS Evidence on the use of systemic treatments for older patients with cancer is increasing, especially for newer options including immune checkpoint inhibitors and targeted agents that provide comparable benefit in older and younger patients. Nonetheless, the risks for short- and long-term toxicities need to be considered. More research is warranted and represents a unique opportunity to increase the knowledge on cancer treatment for older adults. Healthy, older individuals should be considered for standard systemic treatment options, whereas those at risk based on geriatric assessments require adjusted plans. Geriatric assessments are key for decision-making.
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Affiliation(s)
- Nicolò Matteo Luca Battisti
- Department of Medicine, The Royal Marsden NHS Foundation Trust, Downs Road, Sutton, London, SM2 5PT, UK. .,Breast Cancer Research Division, The Institute of Cancer Research, 15 Cotswold Road, Sutton, London, SM2 5NG, UK.
| | - Gabor Liposits
- Department of Oncology, Regional Hospital West Jutland, Gl Landevej 61, 7400, Herning, Denmark
| | - Nienke Aafke De Glas
- Department of Medical Oncology, Leiden University Medical Center, Albinusdreef 2, 2333, Leiden, ZA, Netherlands
| | - Fabio Gomes
- Medical Oncology, The Christie NHS Foundation Trust, Wilmslow Road, Manchester, M20 4BX, UK
| | - Capucine Baldini
- Drug Development Department, Institut Gustave Roussy, Gustave Roussy Cancer Campus, 114 Rue Edouard Vaillant, 94800, Villejuif, France
| | - Supriya Mohile
- Division of Hematology/Oncology, James P. Wilmot Cancer Institute, University of Rochester Medical Center, 601 Elmwood Ave # 704, Rochester, NY, 14642, USA
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20
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Aparicio T, Canouï-Poitrine F, Caillet P, François E, Cudennec T, Carola E, Albrand G, Bouvier AM, Petri C, Couturier B, Phelip JM, Bengrine-Lefevre L, Paillaud E. Treatment guidelines of metastatic colorectal cancer in older patients from the French Society of Geriatric Oncology (SoFOG). Dig Liver Dis 2020; 52:493-505. [PMID: 32029404 DOI: 10.1016/j.dld.2019.12.145] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/01/2019] [Revised: 12/21/2019] [Accepted: 12/23/2019] [Indexed: 12/11/2022]
Abstract
BACKGROUND Several guidelines dedicated to metastatic colorectal cancer (mCRC) are available. Since 2013 no recent guidelines are specifically dedicated to older patients and based on a systematic review. MATERIALS AND METHODS A multidisciplinary Task Force with digestive oncologists, geriatricians and methodologists from the SoFOG was formed in 2016 to update recommendations on medical treatment of mCRC based on a systematic review of publications from 2000 to 2018. Search strategy has followed a standardized protocol from the formulation of clinical questions and definition of a search algorithm to the selection of complete articles for recommendations. RESULTS The four selected key questions were: For which older patients with mCRC can we considered: (1) Any chemotherapy, (2) Mono or poly-chemotherapy, (3) Anti-angiogenic therapy, (4) Other targeted therapy. Main recommendations for older patients are: (1) Omission of chemotherapy should be discussed with a geriatrician for patients with severe comorbidities, advanced dementia, uncontrolled psychiatric disorder or severe loss of autonomy. (2) If tumor response is not the main aim, a mono-chemotherapy with 5-fluorouracil combined with bevacizumab is recommended as first-line. (3) For patients with symptoms related to metastases or with a planned metastasis ablation, a doublet chemotherapy combined with bevacizumab or anti-EGFR antibody in the context of a RAS wild type tumor is recommended as first-line. Preliminary data suggest that regorafenib may be used, in its registered indication, in patients under 80 with a performance status of 0 and no autonomy alterations and that trifluridine-tipiracil may be used with a tight supervising of hematological function.
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Affiliation(s)
- Thomas Aparicio
- Department of Gastroenterology and Digestive Oncology, Saint Louis Hospital, AP-HP, University of Paris, Paris, France.
| | - Florence Canouï-Poitrine
- Clinical Epidemiology and Ageing Unit, Henri Mondor Hospital, APHP, EA 7376, CEpiA- IMRB, University of Paris-Est, Créteil, France
| | - Philippe Caillet
- Department of Geriatry, Georges Pompidou Hospital, APHP, University of Paris, Paris, France
| | - Eric François
- Department of Medical Oncology, Antoine-Lacassagne Center, University Côte d'Azur, Nice, France
| | - Tristan Cudennec
- Department of Geriatry, Ambroise Paré Hospital, APHP, University Versailles - Saint Quentin, Boulogne-Billancourt, France
| | - Elisabeth Carola
- Department of Medical Oncology, Public Sud de l'Oise Hospital, Creil, France
| | - Gilles Albrand
- Department of Geriatry, Lyon-Sud Hospital, Hospices Civils de Lyon, Pierre Bénite, France
| | - Anne-Marie Bouvier
- Digestive Cancer Registry of Burgundy, INSERM UMR1231 EPICAD University of Burgundy Franche Comté, Dijon, France
| | - Camille Petri
- Clinical Epidemiology and Ageing Unit, Henri Mondor Hospital, APHP, EA 7376, CEpiA- IMRB, University of Paris-Est, Créteil, France
| | - Bérengère Couturier
- Clinical Epidemiology and Ageing Unit, Henri Mondor Hospital, APHP, EA 7376, CEpiA- IMRB, University of Paris-Est, Créteil, France
| | - Jean-Marc Phelip
- Department of Gastroenterology and Digestive Oncology, Saint-Etienne Hospital, University Jean Monnet, Saint-Priest-en-Jarez, France
| | | | - Elena Paillaud
- Department of Geriatry, Georges Pompidou Hospital, APHP, University of Paris, Paris, France
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21
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Bai SX, Zhang RR, Chen WH, Dong HM, Wang G, Li XK, Wang W. Clinical efficacy and safety of nimotuzumab plus chemotherapy in patients with advanced colorectal cancer: a retrospective analysis. J Int Med Res 2020; 48:300060519895858. [PMID: 31948326 PMCID: PMC7113702 DOI: 10.1177/0300060519895858] [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] [Indexed: 11/15/2022] Open
Abstract
Objective To compare the clinical efficacy and safety of nimotuzumab combined with chemotherapy versus chemotherapy alone as first-line treatment for advanced colorectal cancer (ACRC). Method We retrospectively enrolled patients with ACRC treated with nimotuzumab plus chemotherapy (n = 40) or chemotherapy alone (n = 44). Responses were evaluated according to the Response Evaluation Criteria in Solid Tumors and adverse events according to the Common Terminology Criteria for Adverse Events 3.0. Results The objective overall response rate and disease control rate were higher in the combined-treatment group (55.0% vs 36.4% and 85.0% vs 75.0%, respectively), but the differences were not significant. There was no significant difference in median progression-free survival or median survival time between the combined-treatment and chemotherapy-alone groups (9.89 vs 7.86 months and 22.32 vs 18.10 months, respectively). There was no significant difference in adverse events between the two groups. Conclusion Nimotuzumab combined with chemotherapy had similar efficacy and safety to chemotherapy alone in patients with ACRC. The efficacy and safety of the combined treatment should be further studied in a randomized multicenter trial with a larger number of patients with ACRC.
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Affiliation(s)
- Sai-Xi Bai
- Department of Abdominal Oncology, Guizhou Cancer Hospital, Guiyang, China
| | - Ruo-Rong Zhang
- Clinical Medical College, Guizhou Medical University, Guiyang, China
| | - Wang-Hua Chen
- Department of Oncology, Affiliated Hospital of Guizhou Medical University, Guiyang, China
| | - Hong-Min Dong
- Department of Oncology, Affiliated Hospital of Guizhou Medical University, Guiyang, China
| | - Gang Wang
- Department of Oncology, Affiliated Hospital of Guizhou Medical University, Guiyang, China
| | - Xiao-Kai Li
- Department of Oncology, Affiliated Hospital of Guizhou Medical University, Guiyang, China
| | - Wenling Wang
- Department of Oncology, Affiliated Hospital of Guizhou Medical University, Guiyang, China
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Rosati G, Addeo R, Aprile G, Avallone A, Bilancia D, Brugnatelli S, Buccafusca G, Carlomagno C, Cordio S, Delfanti S, Dell'Aquila E, Di Bisceglie M, Di Donato S, Di Stasi A, Germano D, Giuliani F, Granetto C, Latiano TP, Leo S, Tralongo P, Stroppolo ME, Venturini F, Bianco S. Italian survey on cetuximab-based therapy of elderly patients with metastatic colorectal cancer. Cancer Chemother Pharmacol 2019; 84:1089-1096. [PMID: 31493178 DOI: 10.1007/s00280-019-03943-x] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/14/2019] [Accepted: 08/24/2019] [Indexed: 02/07/2023]
Abstract
PURPOSE There is no consensus on the use of cetuximab in elderly patients with metastatic colorectal cancer. To this end, a survey was carried in 17 Italian oncology centers. METHODS The centers answered a 29-item questionnaire structured as follows: (i) demographic characteristics; (ii) medical history; (iii) assessment of RAS/BRAF mutations and DPD/UGT polymorphism before treatment; (iv) treatment schemes and side effects; (v) geriatric assessment and customization of treatment. RESULTS One-third of patients are over 80 years old. The RAS/BRAF mutational status is not primarily evaluated by 17.6% of the centers, while DPD and UGT polymorphism is not evaluated by 82.4% and 76.5% of the centers. The most common therapeutic scheme is cetuximab/FOLFIRI and diarrhea is the main cause of suspension/reduction of treatment. The 70% of centers use systemic tetracyclines for skin toxicity. The 23.5% of the centers do not carry out any geriatric evaluation before the start of the therapy and those who perform it prefer the G8 (70.6%) and VES-13 (29.4%) scales. CONCLUSIONS Greater efforts should be made to improve the evaluation of the patient both about mutational and genetic procedures with geriatric evaluation. As for cetuximab in elderly patients, randomized studies are needed to provide guidance to physicians.
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Affiliation(s)
- Gerardo Rosati
- U.O. Oncologia Medica, Azienda Ospedaliera S. Carlo, Potenza, Italy.
| | - Raffaele Addeo
- U.O. Oncologia Medica, Ospedale "San Giovanni di Dio", ASL NA 2 NORD, Frattamaggiore, Italy
| | - Giuseppe Aprile
- Dipartimento di Oncologia Clinica, Ospedale San Bortolo, AULSS8, Vicenza, Italy
| | - Antonio Avallone
- Unità Oncologia Clinica Sperimentale Addome, Dipartimento Assistenziale e di Ricerca dei Percorsi Oncologici del Distretto Addominale, INT Fondazione 'G. Pascale', Naples, Italy
| | | | - Silvia Brugnatelli
- S.C. Oncologia Medica, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy
| | | | - Chiara Carlomagno
- Dipartimento di Medicina Clinica e Chirurgia, Università Federico II, Naples, Italy
| | - Stefano Cordio
- S.C. Oncologia Medica, Ospedale Garibaldi, Catania, Italy
| | - Sara Delfanti
- S.C. Oncologia Medica, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy
| | | | | | | | | | | | | | | | - Tiziana Pia Latiano
- Dipartimento di Oncologia Medica, Ospedale Casa Sollievo della Sofferenza, San Giovanni Rotondo, FG, Italy
| | | | - Paolo Tralongo
- U.O. Oncologia Medica, Ospedale Umberto I - RAO, Siracusa, Italy
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Current Trends in Systemic Therapies in Elderly Patients With Metastatic Colorectal Cancer. CURRENT COLORECTAL CANCER REPORTS 2019. [DOI: 10.1007/s11888-019-00436-0] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/31/2023]
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24
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Carrato A, Benavides M, Massutí B, Ferreiro-Monteagudo R, García Alfonso P, Falcó E, Reboredo M, Cano T, Gallego J, Viéitez JM, Layos L, Salud A, Polo E, Dotor E, Durán-Ogalla G, Rodriguez-Garrote M, Calvo A, Grande E, Aranda E. First-line single-agent regorafenib in frail patients with metastatic colorectal cancer: a pilot phase II study of the Spanish Cooperative Group for the Treatment of Digestive Tumours (TTD). BMC Cancer 2019; 19:533. [PMID: 31159765 PMCID: PMC6547483 DOI: 10.1186/s12885-019-5753-7] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/04/2018] [Accepted: 05/27/2019] [Indexed: 12/13/2022] Open
Abstract
BACKGROUND Treatment of frail patients with advanced colorectal cancer (CRC) is controversial. This pilot phase II trial aimed to assess the efficacy and safety of regorafenib when administered in first-line to frail patients with advanced CRC. METHODS Frail patients without prior advanced colorectal cancer treatment were included in the study. Definition of frailty was defined per protocol based on dependency criteria, presence of chronic comorbid pathologies and/or geriatric features. MAIN OBJECTIVE to assess progression-free survival (PFS) rate at 6 months. Treatment consisted of 28-day cycles of orally administered regorafenib 160 mg/day (3 weeks followed by 1 week rest). RESULTS Forty-seven patients were included in the study. Median age was 81 years (range 63-89). Frailty criteria: dependency was observed in 26 patients (55%), comorbidities in 27 (57%) and geriatric features in 18 (38%). PFS rate at 6 months was 45% (95% confidence interval [CI] 30-60]. Median PFS was 5.6 months (95%CI 2.7-8.4). Median overall survival (OS) was 16 months (95%CI 7.8-24). Complete response, partial response and stable disease were observed in one, two and 21 patients respectively (objective response rate 6.4%; disease control rate 51%). Thirty-nine patients (83%) experienced grade 3-4 adverse events (AEs). The most common grade 3-4 AEs were hypertension (15 patients; 32%), asthenia (14; 30%), hypophosphatemia (6; 13%); diarrhea (4; 8%), hand-foot-skin reaction (4; 8%). There were two toxic deaths (4.2%) (grade 5 rectal bleeding and death not further specified). Dose reduction was required in 26 patients (55%) and dose-delays in 13 patients (28%). CONCLUSIONS The study did not meet the pre-specified boundary of 55% PFS rate at 6 months. Toxicity observed (83% patients experienced grade 3 and 4 AEs) preclude its current use in clinical practice on this setting. Disease control rate and overall survival results are interesting and might warrant further investigation to identify those who benefit from this approach. TRIAL REGISTRATION This trial was prospectively registered at EudraCT ( 2013-000236-94 ). Date of trial registration: April 9th, 2013.
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Affiliation(s)
- A. Carrato
- Medical Oncology Department, Hospital Universitario Ramón y Cajal, IRYCIS, CIBERONC, Alcala University, Ctra. De Colmenar Viejo, km 9,100, 28034 Madrid, Spain
| | - M. Benavides
- Hospital Regional Universitario Virgen de la Victoria, Málaga, Spain
| | - B. Massutí
- Hospital General Universitario de Alicante, Alicante, Spain
| | - R. Ferreiro-Monteagudo
- Medical Oncology Department, Hospital Universitario Ramón y Cajal, IRYCIS, CIBERONC, Alcala University, Ctra. De Colmenar Viejo, km 9,100, 28034 Madrid, Spain
| | | | - E. Falcó
- Hospital Son Llatzer, Mallorca, Spain
| | - M. Reboredo
- Complejo Hospitalario Universitario A Coruña, La Coruña, Spain
| | - T. Cano
- Hospital Universitario Reina Sofia, IMIBIC, University of Córdoba, CIBERONC, Instituto de Salud Carlos III, Córdoba, Spain
| | - J. Gallego
- Hospital General Universitario de Elche, Alicante, Spain
| | - J. M. Viéitez
- Hospital Universitario Central de Asturias, Oviedo, Spain
| | - L. Layos
- Hospital Germans Trias i Pujol, ICO, Badalona, Spain
| | - A. Salud
- Hospital de Lleida Arnau de Vilanova, Lérida, Spain
| | - E. Polo
- Hospital Miguel Servet, Zaragoza, Spain
| | - E. Dotor
- Corporació Sanitària Parc Taulí, Barcelona, Spain
| | - G. Durán-Ogalla
- Hospital Regional Universitario Virgen de la Victoria, Málaga, Spain
| | - M. Rodriguez-Garrote
- Medical Oncology Department, Hospital Universitario Ramón y Cajal, IRYCIS, CIBERONC, Alcala University, Ctra. De Colmenar Viejo, km 9,100, 28034 Madrid, Spain
| | - A. Calvo
- Hospital Gregorio Marañón, Madrid, Spain
| | - E. Grande
- Medical Oncology Department, Hospital Universitario Ramón y Cajal, IRYCIS, CIBERONC, Alcala University, Ctra. De Colmenar Viejo, km 9,100, 28034 Madrid, Spain
| | - E. Aranda
- Hospital Universitario Reina Sofia, IMIBIC, University of Córdoba, CIBERONC, Instituto de Salud Carlos III, Córdoba, Spain
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Moriwaki T, Sakai Y, Ishida H, Yamamoto Y, Endo S, Kuramochi H, Sato M, Hatachi Y, Bando Y, Maeba T, Ikezawa K, Shimada M, Amagai K, Morimoto M, Kobayashi K, Tsuji A, Nishina T, Hyodo I. Phase II study of S-1 on alternate days plus bevacizumab in patients aged ≥ 75 years with metastatic colorectal cancer (J-SAVER). Int J Clin Oncol 2019; 24:1214-1222. [PMID: 31089842 DOI: 10.1007/s10147-019-01465-3] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/28/2019] [Accepted: 05/04/2019] [Indexed: 11/24/2022]
Abstract
BACKGROUND Alternate-day administration of S-1 is thought to reduce toxicities. This phase II study evaluated S-1 on alternate days combined with bevacizumab as first-line treatment for elderly patients with metastatic colorectal cancer. PATIENTS AND METHODS Eligible patients had histologically proven colorectal adenocarcinoma, measurable metastatic lesions, age ≥ 75 years, Eastern Cooperative Oncology Group performance status ≤ 1, no previous chemotherapy, and refused oxaliplatin- or irinotecan-containing regimens. Patients received 40 mg, 50 mg, or 60 mg (body surface area ≤ 1.25 m2, > 1.25 to ≤ 1.50 m2, or > 1.50 m2, respectively) of S-1 twice orally on Sunday, Monday, Wednesday, and Friday every week. Bevacizumab (7.5 mg/kg) was administered every 3 weeks. The primary endpoint was progression-free survival. RESULTS Of 54 enrolled patients, 50 patients were evaluated for efficacy and 53 for safety. The median age was 79 years (range 75-88 years). The median progression-free survival was 8.1 months (95% confidence interval (CI) 6.7-9.5 months). The median overall survival was 23.1 months (95% CI 17.4-28.8 months). The response rate was 44% (95% CI 30.2-57.8%), and the disease control rate was 88% (95% CI 79.0-97.0%). Grade 3 or higher hematologic, non-hematologic, and bevacizumab-related adverse events occurred in 9%, 11%, and 25% of patients, respectively. The most common grade 3 and 4 treatment-related adverse events were hypertension (11%), nausea (6%), fatigue (6%), anemia (6%), and proteinuria (6%). Only 6 patients discontinued treatment due to adverse events. CONCLUSION S-1 on alternate days combined with bevacizumab showed better tolerability and comparable survival compared with the results of similar studies.
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Affiliation(s)
- Toshikazu Moriwaki
- Division of Gastroenterology, Faculty of Medicine, University of Tsukuba, 1-1-1, Tennodai, Tsukuba, 305-8575, Ibaraki, Japan.
| | - Yoshinori Sakai
- Department of Gastroenterology, Tsuchiura Kyodo General Hospital, Tsuchiura City, Ibaraki, Japan
| | - Hiroyasu Ishida
- Department of Gastroenterology, National Hospital Organization Mito Medical Center, Higashi Ibaraki-Gun, Ibaraki, Japan
| | - Yoshiyuki Yamamoto
- Division of Gastroenterology, Faculty of Medicine, University of Tsukuba, 1-1-1, Tennodai, Tsukuba, 305-8575, Ibaraki, Japan
| | - Shinji Endo
- Division of Gastroenterology and Hepatology, Shinmatsudo Central General Hospital, Matsudo City, Chiba, Japan
| | - Hideaki Kuramochi
- Department of Chemotherapy, Yachiyo Medical Center, Tokyo Women's University, Yachiyo City, Chiba, Japan
| | - Mikio Sato
- Department of Gastroenterology and Hepatology, Ryugasaki Saiseikai Hospital, Ryugasaki City, Ibaraki, Japan
| | - Yukimasa Hatachi
- Department of Medical Oncology, Kobe City Medical Center General Hospital, Kobe City, Hyogo, Japan
| | - Yoshiaki Bando
- Department of Surgery, Tokushima Prefecture Naruto Hospital, Naruto City, Tokushima, Japan
| | - Takashi Maeba
- Department of Surgery, Japan Community Health Care Organization Ritsurin Hospital, Takamatsu City, Kagawa, Japan
| | - Kazuto Ikezawa
- Division of Gastroenterology, Department of Internal Medicine, Tsukuba Memorial Hospital, Tsukuba City, Ibaraki, Japan
| | - Mitsuo Shimada
- Department of Surgery, Tokushima University, Tokushima City, Tokushima, Japan
| | - Kenji Amagai
- Division of Gastroenterology and G.I. Oncology, Ibaraki Prefectural Central Hospital and Cancer Center, Kasama City, Ibaraki, Japan
| | | | - Kazuma Kobayashi
- Department of Surgery, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki City, Nagasaki, Japan
| | - Akihito Tsuji
- Department of Clinical Oncology, Faculty of Medicine, Kagawa University, Kita-gun, Kagawa, Japan
| | - Tomohiro Nishina
- Department of Gastrointestinal Medical Oncology, National Hospital Organization Shikoku Cancer Center, Matsuyama City, Ehime, Japan
| | - Ichinosuke Hyodo
- Division of Gastroenterology, Faculty of Medicine, University of Tsukuba, 1-1-1, Tennodai, Tsukuba, 305-8575, Ibaraki, Japan
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Kienle DL, Dietrich D, Ribi K, Wicki A, Quagliata L, Winterhalder RC, Koeberle D, Horber D, Bastian S, Kueng M, Saletti P, Helbling D, Baertschi D, Lugli A, Bernhard J, Andrieu C, von Moos R. Cetuximab monotherapy and cetuximab plus capecitabine as first-line treatment in older patients with RAS- and BRAF wild-type metastatic colorectal cancer. Results of the multicenter phase II trial SAKK 41/10. J Geriatr Oncol 2019; 10:304-310. [DOI: 10.1016/j.jgo.2018.11.011] [Citation(s) in RCA: 17] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/27/2018] [Revised: 10/23/2018] [Accepted: 11/30/2018] [Indexed: 02/07/2023]
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27
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Asimakopoulou N, Souglakos J, Kentepozidis N, Karampeazis A, Kotsakis A, Ziras N, Makrantonakis P, Prinarakis E, Vamvakas L, Georgoulias V. Efficacy of panitumumab in older patients with metastatic colorectal cancer: a retrospective analysis using the database of the Hellenic Oncology Research Group (HORG). J Geriatr Oncol 2019; 10:143-148. [DOI: 10.1016/j.jgo.2018.08.002] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/30/2018] [Revised: 05/03/2018] [Accepted: 08/01/2018] [Indexed: 01/09/2023]
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Sampson B, Lewis BKH. Paronychia Associated with Ledipasvir/Sofosbuvir for Hepatitis C Treatment. THE JOURNAL OF CLINICAL AND AESTHETIC DERMATOLOGY 2019; 12:35-37. [PMID: 30881576 PMCID: PMC6405246] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Subscribe] [Scholar Register] [Indexed: 06/09/2023]
Abstract
We present a case of medication-associated paronychia involving multiple toenails in a patient undergoing hepatitis C (HCV) therapy with ledipasvir/sofosbuvir. The patient was treated conservatively with topical mupirocin, clobetasol ointment, and acetic acid soaks, resulting in symptom improvement and control. This topical regimen was maintainined throughout the remaining weeks of the patient's antiviral course, with complete symptom resolution occurring only after completion of his ledipasvir/sofosbuvir treatment.
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Affiliation(s)
- Blake Sampson
- Dr. Sompson is with the Oregon MedicoI Group in Eugene/Springfield, Oregon (with the Deportment of Dermatology at University of Utah in Salt Lake City, Utah (at the time of this work)
- Dr. Lewis is with the Department of Dermatology at University of Utah in Salt Lake City, Utah
| | - Bethany K H Lewis
- Dr. Sompson is with the Oregon MedicoI Group in Eugene/Springfield, Oregon (with the Deportment of Dermatology at University of Utah in Salt Lake City, Utah (at the time of this work)
- Dr. Lewis is with the Department of Dermatology at University of Utah in Salt Lake City, Utah
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29
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Rosati G, Pinto C, Di Fabio F, Chiara S, Lolli IR, Ruggeri EM, Ciuffreda L, Ferrara R, Antonuzzo L, Adua D, Racca P, Bilancia D, Benincasa E, Stroppolo ME, Di Costanzo F. Quality of life, compliance, safety and effectiveness in fit older metastatic colorectal patients with cancer treated in first-line with chemotherapy plus cetuximab: A restrospective analysis from the ObservEr study. J Geriatr Oncol 2018; 9:243-248. [DOI: 10.1016/j.jgo.2018.01.009] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/27/2017] [Revised: 01/08/2018] [Accepted: 01/23/2018] [Indexed: 01/05/2023]
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30
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Boudrias-Dalle E, Cloutier M, Harvey M, Leblanc G, Besner-Morin O, Adam JP. Durable complete remission following anti-EGFR antibodies in recurrent metastatic colorectal cancer. J Oncol Pharm Pract 2017; 25:239-243. [PMID: 28950807 DOI: 10.1177/1078155217730130] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/16/2022]
Abstract
In this case report, we describe a patient who remains in complete remission two years after the discontinuation of anti-EGFR monotherapy as a third-line treatment, accompanied by persistent severe hypomagnesemia. A 45-year-old Caucasian woman with mCRC started chemotherapy with weekly cetuximab. After ten months of treatment, the therapy was stopped because the patient had persistent grade III hypomagnesemia despite amiloride, oral, and intravenous magnesium. A month later, the patient was switched to panitumumab 6 mg/kg every two weeks for four additional months to avoid weekly visits to the clinic. Following discontinuation of panitumumab, PET scans remain negative to this day, two years after anti-EGFR therapy discontinuation. No factor has been identified to explain the complete and sustained response experienced by this patient. Hypomagnesemia is a common adverse effect of anti-EGFR therapy that can lead to treatment interruption and discontinuation if severe. This case highlights the importance of pursuing anti-EGFR therapy when a response is observed in spite of severe hypomagnesemia. It also provides preliminary information that anti-EGFR therapy could be stopped after a complete response is obtained.
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Affiliation(s)
| | - Magali Cloutier
- 1 Faculty of pharmacy, University of Montreal, Montréal, QC, Canada
| | - Marjorie Harvey
- 1 Faculty of pharmacy, University of Montreal, Montréal, QC, Canada
| | - Guy Leblanc
- 2 Department of Surgery, 60301 Maisonneuve-Rosemont Hospital , University of Montreal, Montreal, Canada
| | - Olivier Besner-Morin
- 3 Department of Pharmacy, 60301 Maisonneuve Rosemont Hospital , Montréal, QC, Canada
| | - Jean-Philippe Adam
- 4 Department of Pharmacy, Centre Hospitalier de l'Université de Montréal, Montréal, QC, Canada.,5 Centre de recherche du Centre Hospitalier de l'Université de Montréal, Montréal, QC, Canada
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31
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Targeted Therapies in Elderly Patients with Metastatic Colorectal Cancer: A Review of the Evidence. Drugs Aging 2017; 34:173-189. [PMID: 28197947 DOI: 10.1007/s40266-017-0439-9] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/05/2023]
Abstract
Metastatic colorectal cancer (mCRC) is the third leading cause of cancer deaths worldwide. As the population of the western world ages, the incidence of colorectal tumours among elderly patients is increasing and consequently so is the demand for treatments for elderly patients. Unfortunately, elderly patients (≥65 years) often go untreated and they are also under-represented in clinical trials. Yet there is some evidence suggesting that 'fit' elderly patients have similar outcomes and tolerance to chemotherapy treatment to their younger counterparts (although the definition of fitness in the elderly population is still a matter of debate). The evidence supporting the administration of new targeted therapies in patients older than 65 years is scarce and more research is needed. In this paper, we review all the available data concerning the use of targeted therapies for mCRC in patients older than 65 years of age and discuss the differences between this age subgroup and younger patients.
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32
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Martinelli E, Cardone C, Troiani T, Normanno N, Pisconti S, Sforza V, Bordonaro AR, Rachiglio AM, Lambiase M, Latiano TP, Modoni G, Cordio S, Giuliani F, Biglietto M, Montesarchio V, Barone C, Tonini G, Cinieri S, Febbraro A, Rizzi D, De Vita F, Orditura M, Colucci G, Maiello E, Ciardiello F, Iaffaioli V, Nasti G, Nappi A, Botti G, Tatangelo F, Chicchinelli N, Montrone M, Sebastio A, Guarino T, Simone G, Graziano P, Chiarazzo C, Maggio G, Longhitano L, Manusia M, Cartenì G, Nappi O, Micheli P, Leo L, Rossi S, Cassano A, Tommaselli E, Giordano G, Sponziello F, Marino A, Rinaldi A, Romito S, Muda AO, Lorusso V, Leo S, Barni S, Grimaldi G, Aieta M. Clinical activity and tolerability of FOLFIRI and cetuximab in elderly patients with metastatic colorectal cancer in the CAPRI-GOIM first-line trial. ESMO Open 2017; 1:e000086. [PMID: 28848656 PMCID: PMC5548975 DOI: 10.1136/esmoopen-2016-000086] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/21/2016] [Accepted: 07/13/2016] [Indexed: 12/22/2022] Open
Abstract
BACKGROUND In the cetuximab after progression in KRAS wild-type colorectal cancer patients (CAPRI) trial patients with metastatic colorectal cancer (mCRC) received 5-fluorouracil, folinic acid and irinotecan (FOLFIRI) and cetuximab in first line followed by 5-Fluorouracil, folinic acid, oxaliplatin (FOLFOX) with or without cetuximab until progression. Limited data are available on the efficacy and safety of anti-epidermal growth factor receptor (anti-EGFR) agents on elderly patients with mCRC. In the current study we evaluated the efficacy and safety of FOLFIRI plus cetuximab in age-defined subgroups. METHODS A post-hoc analysis was performed in CAPRI trial patients; outcomes (progression-free survival (PFS), overall response rate (ORR), safety) were analysed by age-groups and stratified according to molecular characterisation. 3 age cut-offs were used to define the elderly population (≥65; ≥70 and ≥75 years). RESULTS 340 patients with mCRC were treated in first line with FOLFIRI plus cetuximab. Among those, 154 patients were >65 years, 86 >70 years and 35 >75 years. Next-generation sequencing (NGS) was performed in 182 patients. Among them, 87 patients were >65 years, 46 >70 and 17 >75. 104 of 182 patients were wild type (WT) for KRAS, NRAS, BRAF, PIK3CA genes. In the quadruple WT group, 51 patients were ≥65 years; 29 were ≥70; 9 were ≥75. Median PFS was similar within the age-subgroups in the intention-to-treat population, NGS cohort and quadruple WT patients, respectively. Likewise, ORR was not significantly different among age-subgroups in the 3 populations. Safety profile was acceptable and similarly reported among all age-groups, with the exception of grade ≥3 diarrhoea (55% vs 25%, p=0.04) and neutropaenia (75% vs 37%, p=0.03) in patients ≥75 years and grade ≥3 fatigue (31% vs 20%, p=0.01) in patients <75 years. CONCLUSIONS Tolerability of cetuximab plus FOLFIRI was acceptable in elderly patients. Similar ORR and PFS were observed according to age-groups. No differences in adverse events were reported among the defined subgroups with the exception of higher incidence of grade ≥3 diarrhoea and neutropaenia in patients ≥75 years and grade ≥3 fatigue in patients <75 years. TRIAL REGISTRATION NUMBER 2009-014041-81.
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Affiliation(s)
- E Martinelli
- Medical Oncology, Department of Clinical and Experimental Medicine "F. Magrassi", Universitá degli Studi della Campania "Luigi Vanvitelli" , Naples, Italy.
| | - C Cardone
- Medical Oncology, Department of Clinical and Experimental Medicine "F. Magrassi", Universitá degli Studi della Campania "Luigi Vanvitelli" , Naples, Italy
| | - T Troiani
- Medical Oncology, Department of Clinical and Experimental Medicine "F. Magrassi", Universitá degli Studi della Campania "Luigi Vanvitelli" , Naples, Italy
| | - N Normanno
- Cell Biology and Biotherapy Unit, National Cancer Institute "Fondazione Giovanni Pascale", Naples, Italy
| | - S Pisconti
- Department of Medical Oncology, Hospital SS. Annunziata, Taranto, Italy
| | - V Sforza
- Medical Oncology, Department of Clinical and Experimental Medicine "F. Magrassi", Universitá degli Studi della Campania "Luigi Vanvitelli" , Naples, Italy
| | - A R Bordonaro
- Department of Medical Oncology, Hospital Garibaldi, Nesima, Catania, Italy
| | - A M Rachiglio
- Cell Biology and Biotherapy Unit, National Cancer Institute "Fondazione Giovanni Pascale", Naples, Italy; Laboratory of Pharmacogenomics, Centro di Ricerche Oncologiche di Mercogliano (CROM)-National Cancer Institute "Fondazione Giovanni Pascale", Naples, Italy
| | - M Lambiase
- Cell Biology and Biotherapy Unit, National Cancer Institute "Fondazione Giovanni Pascale", Naples, Italy; Laboratory of Pharmacogenomics, Centro di Ricerche Oncologiche di Mercogliano (CROM)-National Cancer Institute "Fondazione Giovanni Pascale", Naples, Italy
| | - T P Latiano
- Department of Medical Oncology, Hospital Casa Sollievo della Sofferenza, San Giovanni Rotondo (Foggia), Italy
| | - G Modoni
- Department of Medical Oncology, Hospital SS. Annunziata, Taranto, Italy
| | - S Cordio
- Department of Medical Oncology, Hospital Garibaldi, Nesima, Catania, Italy
| | - F Giuliani
- Department of Medical Oncology, National Cancer Institute Giovanni Paolo II, Bari,Italy
| | - M Biglietto
- Department of Medical Oncology, Hospital "A. Cardarelli", Naples, Italy
| | - V Montesarchio
- Department of Medical Oncology, Hospital Monaldi- Azienda Ospedaliera dei Colli, Naples,Italy
| | - C Barone
- Department of Medical Oncology, University Hospital A. Gemelli ,Rome, Italy
| | - G Tonini
- Department of Medical Oncology, Policlinico Universitario Campus Bio-Medico, Rome, Italy
| | - S Cinieri
- Department of Medical Oncology, Hospital A. Perrino, Brindisi, Italy
| | - A Febbraro
- Department of Medical Oncology, Hospital Sacro Cuore di Gesù, Fatebenefratelli, Benevento, Italy
| | | | - F De Vita
- Medical Oncology, Department of Clinical and Experimental Medicine "F. Magrassi", Universitá degli Studi della Campania "Luigi Vanvitelli" , Naples, Italy
| | - M Orditura
- Medical Oncology, Department of Clinical and Experimental Medicine "F. Magrassi", Universitá degli Studi della Campania "Luigi Vanvitelli" , Naples, Italy
| | - G Colucci
- Department of Medical Oncology, National Cancer Institute Giovanni Paolo II, Bari,Italy
| | - E Maiello
- Department of Medical Oncology, Hospital Casa Sollievo della Sofferenza, San Giovanni Rotondo (Foggia), Italy
| | - F Ciardiello
- Medical Oncology, Department of Clinical and Experimental Medicine "F. Magrassi", Universitá degli Studi della Campania "Luigi Vanvitelli" , Naples, Italy
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Moth EB, Vardy J, Blinman P. Decision-making in geriatric oncology: systemic treatment considerations for older adults with colon cancer. Expert Rev Gastroenterol Hepatol 2016; 10:1321-1340. [PMID: 27718755 DOI: 10.1080/17474124.2016.1244003] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/08/2023]
Abstract
Colon cancer is common and can be considered a disease of older adults with more than half of cases diagnosed in patients aged over 70 years. Decision-making about treatment with chemotherapy for older adults may be complicated by age-related physiological changes, impaired functional status, limited social supports, concerns regarding the occurrence of and ability to tolerate treatment toxicity, and the presence of comorbidities. This is compounded by a lack of high quality evidence guiding cancer treatment decisions for older adults. Areas covered: This narrative review evaluates the evidence for adjuvant and palliative systemic therapy in older adults with colon cancer. The value of an adequate assessment prior to making a treatment decision is addressed, with emphasis on the geriatric assessment. Guidance in making a treatment decision is provided. Expert commentary: Treatment decisions should consider goals of care, a patient's treatment preferences, and weigh up relative benefits and harms.
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Affiliation(s)
- Erin B Moth
- a Concord Cancer Centre , Concord Repatriation General Hospital , Sydney , Australia.,b Sydney Medical School , University of Sydney , Sydney , Australia
| | - Janette Vardy
- a Concord Cancer Centre , Concord Repatriation General Hospital , Sydney , Australia.,b Sydney Medical School , University of Sydney , Sydney , Australia
| | - Prunella Blinman
- a Concord Cancer Centre , Concord Repatriation General Hospital , Sydney , Australia.,b Sydney Medical School , University of Sydney , Sydney , Australia
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Daste A, Chakiba C, Domblides C, Gross-goupil M, Quivy A, Ravaud A, Soubeyran P. Targeted therapy and elderly people: A review. Eur J Cancer 2016; 69:199-215. [DOI: 10.1016/j.ejca.2016.10.005] [Citation(s) in RCA: 24] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/21/2016] [Accepted: 10/05/2016] [Indexed: 11/26/2022]
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Aparicio T, Pamoukdjian F, Quero L, Manfredi S, Wind P, Paillaud E. Colorectal cancer care in elderly patients: Unsolved issues. Dig Liver Dis 2016; 48:1112-8. [PMID: 27260332 DOI: 10.1016/j.dld.2016.05.011] [Citation(s) in RCA: 27] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/03/2016] [Revised: 04/24/2016] [Accepted: 05/12/2016] [Indexed: 12/11/2022]
Abstract
Colorectal cancers are common in elderly patients. However, cancer screening is poorly used after 75. Elderly patients form a heterogeneous population with specific characteristics. Standards of care cannot therefore be transposed from young to elderly patients. Tumour resection is frequently performed but adjuvant chemotherapy is rarely prescribed as there are no clearly established standards of care. In a metastatic setting, recent phase III studies have demonstrated that doublet front-line chemotherapy provided no survival benefit. Moreover, several studies have established the benefit of bevacizumab in association with chemotherapy. There is a lack of evidence for the efficacy of anti-epidermal growth factor antibodies in elderly patients. Geriatric assessments could help to select the adequate treatment strategy for individual patients. Geriatric oncology is now the challenge we have to face, and more specific trials are needed.
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Affiliation(s)
- Thomas Aparicio
- Gastroenterology and Digestive Oncology Department, CHU Avicenne, APHP, Bobigny, France.
| | | | - Laurent Quero
- Radiotherapy Department, CHU Saint Louis, APHP, Paris, France
| | - Sylvain Manfredi
- Hepato-Gastroenterology and Oncology Department, INSERM U866, CHU Dijon, Dijon, France
| | - Philippe Wind
- Surgery Department, CHU Avicenne, APHP, Bobigny, France
| | - Elena Paillaud
- Geriatric Department, CHU Henri Mondor, APHP, Créteil, France
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36
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Winther SB, Jørgensen TL, Pfeiffer P, Qvortrup C. Can we predict toxicity and efficacy in older patients with cancer? Older patients with colorectal cancer as an example. ESMO Open 2016; 1:e000021. [PMID: 27843604 PMCID: PMC5070237 DOI: 10.1136/esmoopen-2015-000021] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/10/2016] [Revised: 03/08/2016] [Accepted: 03/10/2016] [Indexed: 12/29/2022] Open
Abstract
Colorectal cancer is a disease of the elderly. As older and frail patients are under-represented in clinical trials, most of the evidence available on treatment of older metastatic colorectal patients with cancer originates from pooled analyses of the older patients included in large prospective clinical trials and from community-based studies. The aging process is highly individual and cannot be based on the chronological age alone. It is characterised by a decline in organ function with an increased risk of comorbidity and polypharmacy. These issues can result in an increased susceptibility to the complications of both the disease and treatment. Therefore, evaluation of performance status and the chronological age alone is not sufficient, and additionally assessment must be included in the treatment decision process. In the present review, we will focus on clinical aspects of treating older and frail metastatic colorectal patients with cancer, but also on the present knowledge on how to select and tailor therapy for this particular group of patients. TRIAL REGISTRATION NUMBER EudraCT 2014-000394-39, pre-results.
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Affiliation(s)
- Stine Braendegaard Winther
- Department of Oncology, Odense University Hospital, Odense, Denmark
- Institute of Clinical Research, University of Southern Denmark, Odense, Denmark
| | | | - Per Pfeiffer
- Department of Oncology, Odense University Hospital, Odense, Denmark
- Institute of Clinical Research, University of Southern Denmark, Odense, Denmark
| | - Camilla Qvortrup
- Department of Oncology, Odense University Hospital, Odense, Denmark
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Rosati G, Aprile G, Cardellino GG, Avallone A. A review and assessment of currently available data of the EGFR antibodies in elderly patients with metastatic colorectal cancer. J Geriatr Oncol 2016; 7:134-41. [DOI: 10.1016/j.jgo.2016.01.006] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/02/2015] [Revised: 01/16/2016] [Accepted: 01/29/2016] [Indexed: 12/15/2022]
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Palma S, Zwenger AO, Croce MV, Abba MC, Lacunza E. From Molecular Biology to Clinical Trials: Toward Personalized Colorectal Cancer Therapy. Clin Colorectal Cancer 2015; 15:104-15. [PMID: 26777471 DOI: 10.1016/j.clcc.2015.11.001] [Citation(s) in RCA: 18] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/07/2015] [Revised: 10/30/2015] [Accepted: 11/23/2015] [Indexed: 12/22/2022]
Abstract
During the past years, molecular studies through high-throughput technologies have led to the confirmation of critical alterations in colorectal cancer (CRC) and the discovery of some new ones, including mutations, DNA methylations, and structural chromosomal changes. These genomic alterations might act in concert to dysregulate specific signaling pathways that normally exert their functions on critical cell phenotypes, including the regulation of cellular metabolism, proliferation, differentiation, and survival. Targeted therapy against key components of altered signaling pathways has allowed an improvement in CRC treatment. However, a significant percentage of patients with CRC and metastatic CRC will not benefit from these targeted therapies and will be restricted to systemic chemotherapy. Mechanisms of resistance have been associated with specific gene alterations. To fully understand the nature and significance of the genetic and epigenetic defects in CRC that might favor a tumor evading a given therapy, much work remains. Therefore, a dynamic link between basic molecular research and preclinical studies, which ultimately constitute the prelude to standardized therapies, is very important to provide better and more effective treatments against CRC. We present an updated revision of the main molecular features of CRC and their associated therapies currently under study in clinical trials. Moreover, we performed an unsupervised classification of CRC clinical trials with the aim of obtaining an overview of the future perspectives of preclinical studies.
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Affiliation(s)
- Sabina Palma
- CINIBA, Facultad de Ciencias Médicas, Universidad Nacional de La Plata, La Plata, Argentina
| | - Ariel O Zwenger
- Servicio de Oncología, Hospital Provincial Neuquén, Neuquén, Argentina
| | - María V Croce
- CINIBA, Facultad de Ciencias Médicas, Universidad Nacional de La Plata, La Plata, Argentina
| | - Martín C Abba
- CINIBA, Facultad de Ciencias Médicas, Universidad Nacional de La Plata, La Plata, Argentina
| | - Ezequiel Lacunza
- CINIBA, Facultad de Ciencias Médicas, Universidad Nacional de La Plata, La Plata, Argentina.
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Millan M, Merino S, Caro A, Feliu F, Escuder J, Francesch T. Treatment of colorectal cancer in the elderly. World J Gastrointest Oncol 2015; 7:204-20. [PMID: 26483875 PMCID: PMC4606175 DOI: 10.4251/wjgo.v7.i10.204] [Citation(s) in RCA: 91] [Impact Index Per Article: 9.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/29/2015] [Revised: 06/30/2015] [Accepted: 08/30/2015] [Indexed: 02/05/2023] Open
Abstract
Colorectal cancer has a high incidence, and approximately 60% of colorectal cancer patients are older than 70, with this incidence likely increasing in the near future. Elderly patients (> 70-75 years of age) are a very heterogeneous group, ranging from the very fit to the very frail. Traditionally, these patients have often been under-treated and recruited less frequently to clinical trials than younger patients, and thus are under-represented in publications about cancer treatment. Recent studies suggest that fit elderly patients can be treated in the same way as their younger counterparts, but the treatment of frail patients with comorbidities is still a matter of controversy. Many factors should be taken into account, including fitness for treatment, the wishes of the patient and family, and quality of life. This review will focus on the existing evidence for surgical, oncologic, and palliative treatment in patients over 70 years old with colorectal cancer. Careful patient assessment is necessary in order to individualize treatment approach, and this should rely on a multidisciplinary process. More well-designed controlled trials are needed in this patient population.
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40
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Pietrantonio F, Cremolini C, Aprile G, Lonardi S, Orlandi A, Mennitto A, Berenato R, Antoniotti C, Casagrande M, Marsico V, Marmorino F, Cardellino GG, Bergamo F, Tomasello G, Formica V, Longarini R, Giommoni E, Caporale M, Di Bartolomeo M, Loupakis F, de Braud F. Single-Agent Panitumumab in Frail Elderly Patients With Advanced RAS and BRAF Wild-Type Colorectal Cancer: Challenging Drug Label to Light Up New Hope. Oncologist 2015; 20:1261-5. [PMID: 26446234 DOI: 10.1634/theoncologist.2015-0171] [Citation(s) in RCA: 36] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/26/2015] [Accepted: 08/21/2015] [Indexed: 12/22/2022] Open
Abstract
BACKGROUND No prospective trials have specifically addressed the efficacy and safety of panitumumab in elderly patients with metastatic colorectal cancer (CRC). We aimed at assessing the efficacy and safety of single agent panitumumab in "frail" elderly patients diagnosed with metastatic RAS and BRAF wild-type CRC. MATERIALS AND METHODS Forty elderly patients (aged ≥ 75 years) with metastatic RAS-BRAF wild-type CRC received off-label prescriptions of single-agent panitumumab at seven Italian institutions. Treatment was administered as first line in patients with absolute contraindication to any chemotherapy or as second-line treatment after failure of a fluoropyrimidine-based treatment, in the presence of contraindication to irinotecan. The outcome measures included objective response rate (ORR), as well as progression-free survival (PFS), disease control rate (DCR), overall survival (OS), and safety. RESULTS The median PFS and OS were 6.4 months (95% confidence interval [CI]: 4.9-8 months) and 14.3 months (95% CI: 10.9-17.7 months), respectively. ORR was 32.5%, and DCR was 72.5%. Dose reductions related to adverse events (AEs) were reported in 9 (23%) patients, but no permanent treatment discontinuation caused by was reported. The most frequent grade 3 AE was skin rash, with an incidence of 20%. CONCLUSION Panitumumab is effective and well-tolerated in frail elderly patients with RAS-BRAF wild-type metastatic CRC and deemed unfit for chemotherapy. A randomized study is needed to confirm these data. IMPLICATIONS FOR PRACTICE Treatment of elderly patients with metastatic colorectal cancer represents a difficult challenge in clinical practice. A significant proportion of frail elderly patients do not receive treatment, reflecting ongoing uncertainty of clinical benefit and toxicity of chemotherapy. Unfit condition in this cohort of patients further limits antineoplastic prescription and consequently patient survival. RAS and BRAF wild-type status could help select an elderly and unfit population that could benefit from anti-epidermal growth factor receptor single agent therapy. In the present study, single-agent off-label panitumumab was effective and well-tolerated as first-line treatment in frail elderly patients deemed unfit for chemotherapy for metastatic RAS and BRAF wild-type colorectal cancer.
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Affiliation(s)
- Filippo Pietrantonio
- Medical Oncology Department, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy
| | - Chiara Cremolini
- Polo Oncologico, Azienda Ospedaliero-Universitaria Pisana, Pisa, Italy
| | - Giuseppe Aprile
- Dipartimento di Oncologia, Azienda Ospedaliero-Universitaria di Udine, Udine, Italy
| | - Sara Lonardi
- Unità Operativa Complessa Oncologia Medica 1, Istituto Oncologico Veneto, IRCCS, Padova, Italy
| | - Armando Orlandi
- Medical Oncology Unit, Policlinico Universitario "A. Gemelli," Rome, Italy
| | - Alessia Mennitto
- Medical Oncology Department, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy
| | - Rosa Berenato
- Medical Oncology Department, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy
| | | | | | - Valentina Marsico
- Unità Operativa Complessa Oncologia Medica 1, Istituto Oncologico Veneto, IRCCS, Padova, Italy
| | | | | | - Francesca Bergamo
- Unità Operativa Complessa Oncologia Medica 1, Istituto Oncologico Veneto, IRCCS, Padova, Italy
| | | | - Vincenzo Formica
- Unità di Oncologia Medica, Policlinico Universitario Tor Vergata, Roma, Italy
| | | | - Elisa Giommoni
- Struttura Complessa Oncologia Medica I, Azienda Ospedaliero-Universitaria Careggi, Firenze, Italy
| | - Marta Caporale
- Medical Oncology Department, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy
| | - Maria Di Bartolomeo
- Medical Oncology Department, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy
| | - Fotios Loupakis
- Polo Oncologico, Azienda Ospedaliero-Universitaria Pisana, Pisa, Italy
| | - Filippo de Braud
- Medical Oncology Department, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy
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Abstract
The response to first-line therapy is a primary determinant of outcome in patients with metastatic colorectal cancer (mCRC), for three main reasons: effective upfront therapy provides a unique opportunity to cure some patients; can be crucial in delaying disease progression and achieving symptom relief; and can improve patient eligibility for, and the effectiveness of, further treatments. In the past decade, decision-making regarding the choice of first-line therapy for mCRC has been complicated by the availability of many different options without a definitive consensus on a specific standard of care (despite major advances in categorizing predictive molecular disease subtypes). Most of the efforts of the scientific community have been directed at establishing the best biologic agent to be combined with a chemotherapy doublet, although a different branch of research has produced new data that underscore the importance of defining the optimal chemotherapy backbone. Herein, we review the key clinical trials completed in the past 10 years that have investigated and compared the use of chemotherapy doublets, triplets, and monotherapies, with or without molecularly targeted biologic agents, in the first-line treatment of patients with mCRC. Our examination of the literature led us to propose a new patient-oriented algorithm to guide clinicians' decisions on the best choice of upfront therapy for mCRC.
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42
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Kim JH. Chemotherapy for colorectal cancer in the elderly. World J Gastroenterol 2015; 21:5158-5166. [PMID: 25954089 PMCID: PMC4419056 DOI: 10.3748/wjg.v21.i17.5158] [Citation(s) in RCA: 142] [Impact Index Per Article: 14.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/26/2014] [Revised: 03/02/2015] [Accepted: 04/03/2015] [Indexed: 02/07/2023] Open
Abstract
Colorectal cancer (CRC) is one of the leading causes of cancer-related death in the elderly. However, elderly patients with CRC tend to be under-presented in clinical trials and undertreated in clinical practice. Advanced age alone should not be the only criteria to preclude effective therapy in elderly patients with CRC. The best guide about optimal cancer treatment can be provided by comprehensive geriatric assessment. Elderly patients with stage III colon cancer can enjoy the same benefit from adjuvant chemotherapy with 5-fluorouracil/leucovorin or capecitabine as younger patients, without a substantial increase in toxicity. With conflicting results of retrospective studies and a lack of data available from randomized studies, combined modality treatment should be used with great caution in elderly patients with locally advanced rectal cancer. Combination chemotherapy can be considered for older patients with metastatic CRC. For elderly patients who are frail or vulnerable, however, monotherapy or a stop-and-go strategy may be desirable. The use of targeted therapies in older patients with metastatic CRC appears to be promising in view of their better efficacy and toxicity. Treatment should be individualized based on the nature of the disease, the physiologic or functional status, and the patient’s preference.
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43
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The place of targeted agents in the treatment of elderly patients with metastatic colorectal cancer. Cancers (Basel) 2015; 7:439-49. [PMID: 25782007 PMCID: PMC4381267 DOI: 10.3390/cancers7010439] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/13/2015] [Revised: 03/02/2015] [Accepted: 03/06/2015] [Indexed: 01/05/2023] Open
Abstract
Despite the high prevalence of colorectal cancer in a continuously aging population and the substantial advances in the treatment of metastatic disease during the past decade, the treatment of elderly patients with advanced, unresectable or metastatic colorectal cancer is a clearly unmet need. Since older patients are under-represented or even excluded from randomized trials, the evidence that oncologists use as guidance is weak. However, small prospective studies, pooled analyses and observational studies show that combination approaches are safe, efficacious and feasible in the geriatric population with metastatic colorectal cancer. The use of biologic agents targeting angiogenesis and the epidermal growth factor receptor, which have been shown to clearly improve outcomes in multiple prospective trials in patients with advanced colorectal cancer, is a vital component of the aforementioned combination approaches. Herein, we review all available data concerning the management of elderly patients with these agents and underscore the differences between this age subgroup and younger patients.
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44
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Rosati G, Aprile G, Poletto E, Avallone A. An update on the management of metastatic colorectal cancer in the elderly. COLORECTAL CANCER 2014. [DOI: 10.2217/crc.14.32] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/27/2022]
Abstract
SUMMARY The availability of new chemotherapeutic and targeted agents has changed the life expectancy of patients with metastatic colorectal cancer thanks to the possibility of sequentially administering fluoropyrimidines combined with irinotecan and oxaliplatin plus monoclonal antibodies. This approach is seldom feasible in the elderly, especially because of the poor tolerability of some agents. Frail patients should only receive palliative treatment. Oppositely, fit elderly patients can be treated with more aggressive therapies, similarly to the younger ones. What is not sufficiently known is how to manage the elderly categorized as intermediate. In the coming years, it appears necessary how to accurately differentiate the elderly through a comprehensive geriatric assessment performed with validated scales and uniformed criteria simpler than those currently available.
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Affiliation(s)
- Gerardo Rosati
- Medical Oncology Unit, S. Carlo Hospital, Potenza, Italy
| | - Giuseppe Aprile
- Department of Medical Oncology, University Hospital, Udine, Italy
| | - Elena Poletto
- Department of Medical Oncology, University Hospital, Udine, Italy
| | - Antonio Avallone
- Department of Gastrointestinal Medical Oncology, National Cancer Institute, Naples, Italy
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45
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McCleary NJ, Dotan E, Browner I. Refining the Chemotherapy Approach for Older Patients With Colon Cancer. J Clin Oncol 2014; 32:2570-80. [DOI: 10.1200/jco.2014.55.1960] [Citation(s) in RCA: 42] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/10/2023] Open
Abstract
Population studies support an increased incidence of most cancers among older adults. Colorectal cancer has high prevalence in the aging population, with a median age of 69 years at diagnosis and 74 years at death. The vast majority of patients with colon cancer (CC) will require chemotherapy treatments during their disease course, challenging oncologists with the task of tailoring therapy for older patients with CC in the face of limited evidence-based data to guide them. Factors such as comorbidity, performance status, cognitive function, and social support may affect decision making and complicate tolerance of any recommended therapy. In recent years, attention to the specific needs of the aging population with cancer has given rise to the field of geriatric oncology in general, and has generated an increasing fund of knowledge on which to base chemotherapy delivery for this specific population of patients with CC. This article will review the available data specifically for chemotherapy management of older patients with CC in the postoperative and metastatic settings.
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Affiliation(s)
- Nadine J. McCleary
- Nadine J. McCleary, Dana-Farber Cancer Institute, Boston MA; Efrat Dotan, Fox Chase Cancer Center, Philadelphia, PA; and Ilene Browner, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins, Baltimore, MD
| | - Efrat Dotan
- Nadine J. McCleary, Dana-Farber Cancer Institute, Boston MA; Efrat Dotan, Fox Chase Cancer Center, Philadelphia, PA; and Ilene Browner, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins, Baltimore, MD
| | - Ilene Browner
- Nadine J. McCleary, Dana-Farber Cancer Institute, Boston MA; Efrat Dotan, Fox Chase Cancer Center, Philadelphia, PA; and Ilene Browner, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins, Baltimore, MD
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Papamichael D, Audisio RA, Glimelius B, de Gramont A, Glynne-Jones R, Haller D, Köhne CH, Rostoft S, Lemmens V, Mitry E, Rutten H, Sargent D, Sastre J, Seymour M, Starling N, Van Cutsem E, Aapro M. Treatment of colorectal cancer in older patients: International Society of Geriatric Oncology (SIOG) consensus recommendations 2013. Ann Oncol 2014; 26:463-76. [PMID: 25015334 DOI: 10.1093/annonc/mdu253] [Citation(s) in RCA: 296] [Impact Index Per Article: 26.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022] Open
Abstract
Colorectal cancer (CRC) is one of the most commonly diagnosed cancers in Europe and worldwide, with the peak incidence in patients >70 years of age. However, as the treatment algorithms for the treatment of patients with CRC become ever more complex, it is clear that a significant percentage of older CRC patients (>70 years) are being less than optimally treated. This document provides a summary of an International Society of Geriatric Oncology (SIOG) task force meeting convened in Paris in 2013 to update the existing expert recommendations for the treatment of older (geriatric) CRC patients published in 2009 and includes overviews of the recent data on epidemiology, geriatric assessment as it relates to surgery and oncology, and the ability of older CRC patients to tolerate surgery, adjuvant chemotherapy, treatment of their metastatic disease including palliative chemotherapy with and without the use of the biologics, and finally the use of adjuvant and palliative radiotherapy in the treatment of older rectal cancer patients. An overview of each area was presented by one of the task force experts and comments invited from other task force members.
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Affiliation(s)
- D Papamichael
- Department of Medical Oncology, B.O. Cyprus Oncology Centre, Nicosia, Cyprus
| | | | - B Glimelius
- Department of Radiology, Oncology and Radiation Science, University of Uppsala, Uppsala, Sweden
| | | | | | - D Haller
- Abramson Cancer Center at the University of Pennsylvania, Philadelphia, USA
| | - C-H Köhne
- Klinikum Oldenburg, Oldenburg, Germany
| | - S Rostoft
- Department of Geriatric Medicine, Oslo University Hospital, Oslo, Norway
| | - V Lemmens
- Erasmus MC University Medical Centre, Rotterdam Eindhoven Cancer Registry, Comprehensive Cancer Centre South (IKZ), Eindhoven, The Netherlands
| | - E Mitry
- Department of Medical Oncology, Institut Curie, Paris Université Versailles Saint-Quentin, Guyancourt, France
| | - H Rutten
- Catharina Hospital Eindhoven, Eindhoven Maastricht University Medical Center, Maastricht, The Netherlands
| | | | - J Sastre
- Department of Medical Oncology, Hospital Clinico San Carlos, Madrid, Spain
| | - M Seymour
- Cancer Medicine and Pathology, University of Leeds, Leeds
| | - N Starling
- Gastrointestinal Unit, Royal Marsden Hospital, London, UK
| | - E Van Cutsem
- Digestive Oncology, Leuven Cancer Institute, Leuven, Belgium
| | - M Aapro
- SIOG Office, Clinique de Genolier, Genolier, Switzerland
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Dotan E, Devarajan K, D'Silva AJ, Beck A, Kloth DD, Cohen SJ, Denlinger C. Patterns of use and tolerance of anti-epidermal growth factor receptor antibodies in older adults with metastatic colorectal cancer. Clin Colorectal Cancer 2014; 13:192-8. [PMID: 25074246 DOI: 10.1016/j.clcc.2014.05.003] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/04/2014] [Accepted: 05/19/2014] [Indexed: 01/14/2023]
Abstract
BACKGROUND Limited data are available regarding the tolerance of anti-epidermal growth factor receptor (EGFR) antibodies among elderly patients with metastatic colorectal cancer (mCRC). We retrospectively reviewed our experience of treating elderly patients with mCRC with these agents between 2004 and 2011. METHODS Patients with mCRC ≥ 65 years treated with anti-EGFR agents were included in this analysis. We recorded demographic and disease characteristics, treatment regimen and duration, KRAS status, and overall survival (OS). Toxicity evaluation included common hematologic and nonhematologic toxicities seen with these agents. RESULTS One hundred seventeen patients were included, with a median age at treatment initiation of 73 years (range, 65-86 years), 59% of male sex, 82% with colon primary tumors, and 51% with metastatic disease at presentation. Median time on anti-EGFR treatment was 2.4 months. Older age at treatment initiation was associated with use of anti-EGFR antibody as monotherapy versus combination therapy (P = .0009). Worse performance status (PS) at treatment initiation was associated with a shorter overall survival (OS) (P = .013) and shorter treatment duration (P = .01). The incidence of hematologic/nonhematologic grade ≥ 3 was 36% and 15%, respectively. No association was found between age and presence of grade ≥ 3 toxicity. Longer treatment duration and better PS at treatment initiation were the only factors associated with higher incidence of grade 3 toxicity. CONCLUSION Our data demonstrate that anti-EGFR antibodies can be used in older patients with mCRC, with toxicity profiles similar to those reported in large phase III studies of younger patients. Advanced age was associated with receipt of anti-EGFR agents as monotherapy but did not impact treatment outcomes in this population.
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Affiliation(s)
- Efrat Dotan
- Department of Medical Oncology, Fox Chase Cancer Center, Philadelphia, PA.
| | - Karthik Devarajan
- Department of Biostatistics and Bioinformatics, Fox Chase Cancer Center, Philadelphia, PA
| | - A James D'Silva
- Department of Internal Medicine, Temple University Hospital, Philadelphia, PA
| | - Andrew Beck
- Department of Medical Oncology, Fox Chase Cancer Center, Philadelphia, PA
| | - Dwight D Kloth
- Department of Pharmacy, Fox Chase Cancer Center, Philadelphia, PA
| | - Steven J Cohen
- Department of Medical Oncology, Fox Chase Cancer Center, Philadelphia, PA
| | - Crystal Denlinger
- Department of Medical Oncology, Fox Chase Cancer Center, Philadelphia, PA
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First-line bevacizumab and capecitabine-oxaliplatin in elderly patients with mCRC: GEMCAD phase II BECOX study. Br J Cancer 2014; 111:241-8. [PMID: 24946000 PMCID: PMC4102952 DOI: 10.1038/bjc.2014.346] [Citation(s) in RCA: 28] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/30/2014] [Revised: 05/12/2014] [Accepted: 05/27/2014] [Indexed: 12/13/2022] Open
Abstract
Background: Subgroup analyses of clinical studies suggest that bevacizumab plus XELOX is effective and tolerable in elderly patients with metastatic colorectal cancer (mCRC). The prospective BECOX study examined the efficacy and safety of bevacizumab plus XELOX, followed by bevacizumab plus capecitabine in elderly patients with mCRC. Methods: Patients aged ⩾70 years with Eastern Cooperative Oncology Group performance status 0 out of 1 and confirmed mCRC were included. Patients received bevacizumab 7.5 mg kg−1 and oxaliplatin 130 mg m−2 on day 1, plus capecitabine 1000 mg m−2 bid orally on days 1–14 every 21 days; oxaliplatin was discontinued after 6 cycles. The primary end point was time to progression (TTP). Results: The intent-to-treat population comprised 68 patients (65% male, median age 76 years). Median TTP was 11.1 months; median overall survival was 20.4 months; overall response rate was 46%. Grade 3 or 4 adverse events included diarrhoea (18%) and asthenia (16%). Grade 3 or 4 adverse events of special interest for bevacizumab included deep-vein thrombosis (6%) and pulmonary embolism (4%). Conclusions: Bevacizumab plus XELOX was effective and well tolerated in elderly patients in the BECOX study. The adverse-event profile was similar to previous reports; no new safety concerns were identified. Fit elderly patients with mCRC should be considered for treatment with bevacizumab plus XELOX.
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Aguado C, García-Paredes B, Sotelo MJ, Sastre J, Díaz-Rubio E. Should capecitabine replace 5-fluorouracil in the first-line treatment of metastatic colorectal cancer? World J Gastroenterol 2014; 20:6092-6101. [PMID: 24876731 PMCID: PMC4033448 DOI: 10.3748/wjg.v20.i20.6092] [Citation(s) in RCA: 30] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/21/2013] [Revised: 02/13/2014] [Accepted: 03/19/2014] [Indexed: 02/06/2023] Open
Abstract
Fluoropyrimidines play a central role in the first-line treatment of metastatic colorectal cancer. Our aim was to review whether capecitabine was a safer, non-inferior, economically superior and more convenient alternative to 5-fluorouracil. Capecitabine has previously been compared to 5-fluorouracil-either as a monotherapy or in combination with oxaliplatin, irinotecan, or biological drugs-and has been found to have comparable efficacy and safety profiles. Furthermore, pharmacoeconomic data and patients’ preferences for oral chemotherapy further favor capecitabine. Therefore, capecitabine appears to be an effective and safe alternative to fluorouracil in the first-line treatment of metastatic colorectal cancer.
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Kordatou Z, Kountourakis P, Papamichael D. Treatment of older patients with colorectal cancer: a perspective review. Ther Adv Med Oncol 2014; 6:128-40. [PMID: 24790652 PMCID: PMC3987654 DOI: 10.1177/1758834014523328] [Citation(s) in RCA: 35] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/27/2022] Open
Abstract
In a continuously aging population, the burden of colorectal cancer (CRC) is rising among older patients. Despite the fact that almost half of the cases occur in patients over 75 years, this age group is subjected to disparities regarding diagnostic and therapeutic options. So far, exclusion of older patients from randomized clinical trials has resulted in a lack of evidence-based guidelines. Nevertheless, newer data from studies specifically targeting older patients and subgroup analyses indicate that proper treatment planning and specific medical and geriatric assessment can achieve a safe and beneficial treatment result in older patients, often with similar outcomes to their younger counterparts. Resection of the primary tumour, if feasible, should be the primary goal of surgery aiming for cure, although it should be avoided under emergency conditions. Chronological age per se should not be an exclusion criterion for adjuvant or palliative chemotherapy, or targeted therapies. Careful patient selection, dose adjustments, close monitoring and early intervention in the event of side effects are essential. The benefits of treatment must be balanced with potential effects of treatment and patients' wishes.
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Affiliation(s)
- Z Kordatou
- Department of Medical Oncology, BOC Oncology Centre, Nicosia, Cyprus
| | - P Kountourakis
- Department of Medical Oncology, BOC Oncology Centre, Nicosia, Cyprus
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