|
1
|
Kim M, Powers CA, Fisher DT, Ku AW, Neznanov N, Safina AF, Wang J, Gautam A, Balachandran S, Krishnamurthy A, Gurova KV, Evans SS, Gudkov AV, Skitzki JJ. Enhancing Anti-PD-1 Immunotherapy by Targeting MDSCs via Hepatic Arterial Infusion in Breast Cancer Liver Metastases. Cancers (Basel) 2024; 16:3711. [PMID: 39518148 PMCID: PMC11545300 DOI: 10.3390/cancers16213711] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/17/2024] [Revised: 10/23/2024] [Accepted: 10/30/2024] [Indexed: 11/16/2024] Open
Abstract
BACKGROUND Surgery, chemotherapy, and radiation often have limited utility for advanced metastatic disease in the liver, and despite its promising activity in select cancers, PD-1 blockade therapy similarly has minimal benefit in this setting. Curaxin, CBL0137, is an experimental anti-cancer drug that disrupts the binding of DNA to histones, destabilizes chromatin, and induces Z-DNA formation which may stimulate anti-tumor immune responses. METHODS Murine cell lines of colon (CT26) and breast (4T1) cancer were interrogated for survival and CBL0137-associated DNA changes in vitro. Immunocompetent models of liver metastases followed by CBL0137 hepatic arterial infusion (HAI) were used to examine in vivo tumor cell DNA alterations, treatment responses, and the immune contexture associated with CBL0137, both alone and in combination with anti-PD-1 therapy. RESULTS CBL0137 induced immediate changes to favor tumor cell death in vitro and in vivo with an efficient tumor uptake via the HAI route. Toxicity to CBL0137 was minimal and anti-tumor treatment effects were more efficient with HAI compared to intravenous delivery. Immune effects were pronounced with CBL0137 HAI with concurrent depletion of a specific population of myeloid-derived suppressor cells and maintenance of effector T cell populations. CONCLUSIONS Combination of CBL0137 HAI with PD-1 blockade improved survival in 4T1 tumors but not in CT26 tumors, and therapeutic efficacy relies on the finding of simultaneous and targeted depletion of myeloid-derived suppressor cells and skewing of T cell populations to produce synergy with PD-1 blockade therapy.
Collapse
Affiliation(s)
- Minhyung Kim
- Department of Surgical Oncology, Roswell Park Comprehensive Cancer Center, Buffalo, NY 14263, USA; (C.A.P.); (D.T.F.); (A.W.K.)
- Department of Immunology, Roswell Park Comprehensive Cancer Center, Buffalo, NY 14263, USA;
| | - Colin A. Powers
- Department of Surgical Oncology, Roswell Park Comprehensive Cancer Center, Buffalo, NY 14263, USA; (C.A.P.); (D.T.F.); (A.W.K.)
| | - Daniel T. Fisher
- Department of Surgical Oncology, Roswell Park Comprehensive Cancer Center, Buffalo, NY 14263, USA; (C.A.P.); (D.T.F.); (A.W.K.)
- Department of Immunology, Roswell Park Comprehensive Cancer Center, Buffalo, NY 14263, USA;
| | - Amy W. Ku
- Department of Surgical Oncology, Roswell Park Comprehensive Cancer Center, Buffalo, NY 14263, USA; (C.A.P.); (D.T.F.); (A.W.K.)
- Department of Immunology, Roswell Park Comprehensive Cancer Center, Buffalo, NY 14263, USA;
| | - Nickolay Neznanov
- Department of Cell Stress Biology, Roswell Park Comprehensive Cancer Center, Buffalo, NY 14263, USA; (N.N.); (A.F.S.); (K.V.G.); (A.V.G.)
| | - Alfiya F. Safina
- Department of Cell Stress Biology, Roswell Park Comprehensive Cancer Center, Buffalo, NY 14263, USA; (N.N.); (A.F.S.); (K.V.G.); (A.V.G.)
| | - Jianmin Wang
- Department of Biostatistics & Bioinformatics, Roswell Park Comprehensive Cancer Center, Buffalo, NY 14263, USA;
| | - Avishekh Gautam
- Blood Cell Development and Function Program, Fox Chase Cancer Center, Philadelphia, PA 19111, USA; (A.G.); (S.B.)
| | - Siddharth Balachandran
- Blood Cell Development and Function Program, Fox Chase Cancer Center, Philadelphia, PA 19111, USA; (A.G.); (S.B.)
| | - Anuradha Krishnamurthy
- Department of Medicine, Roswell Park Comprehensive Cancer Center, Buffalo, NY 14263, USA;
| | - Katerina V. Gurova
- Department of Cell Stress Biology, Roswell Park Comprehensive Cancer Center, Buffalo, NY 14263, USA; (N.N.); (A.F.S.); (K.V.G.); (A.V.G.)
| | - Sharon S. Evans
- Department of Immunology, Roswell Park Comprehensive Cancer Center, Buffalo, NY 14263, USA;
| | - Andrei V. Gudkov
- Department of Cell Stress Biology, Roswell Park Comprehensive Cancer Center, Buffalo, NY 14263, USA; (N.N.); (A.F.S.); (K.V.G.); (A.V.G.)
| | - Joseph J. Skitzki
- Department of Surgical Oncology, Roswell Park Comprehensive Cancer Center, Buffalo, NY 14263, USA; (C.A.P.); (D.T.F.); (A.W.K.)
- Department of Immunology, Roswell Park Comprehensive Cancer Center, Buffalo, NY 14263, USA;
| |
Collapse
|
|
2
|
Li J, Yang B, Teng Z, Liu Y, Li D, Qu X. Efficacy and safety of first-line treatments for advanced hepatocellular carcinoma patients: a systematic review and network meta-analysis. Front Immunol 2024; 15:1430196. [PMID: 39355238 PMCID: PMC11442238 DOI: 10.3389/fimmu.2024.1430196] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/09/2024] [Accepted: 08/28/2024] [Indexed: 10/03/2024] Open
Abstract
Background The first-line treatment for advanced hepatocellular carcinoma has evolved significantly. This study aimed to identify the most beneficial regimen. Methods A systematic search was conducted from July 2012 to August 2024 across the following four databases: PubMed, Embase, Cochrane Library, and ClinicalTrials.gov. This search focused on phase III prospective randomized controlled trials that compared first-line treatment for advanced hepatocellular carcinoma. Results Seventeen studies involving 10322 patients were included in this network meta-analysis. Of the studies we included, twelve studies were global multicenter clinical studies, four were initiated in China, and one was initiated in Korea. The results of our statistical analysis suggest that Hepatic artery infusion chemotherapy with oxaliplatin plus fluorouracil (HAIC-FO) demonstrated significant overall survival (OS) benefits compared with most treatments, including various immune checkpoint inhibitors (ICIs) and anti-vascular endothelial growth factor tyrosine kinase inhibitors (VEGF-TKIs). In terms of OS, HAIC had shown similar efficacy with sorafenib plus FOLFOX (HR, 0.88; 95% CI: 0.37-2.09) and transcatheter arterial chemoembolization (TACE) combined with lenvatinib (HR, 0.69; 95% CI: 0.30-1.56). Notably, immune-related treatments, such as ICIs combined with anti-VEGF therapies, also showed improved OS compared with anti-VEGF-TKIs alone. In terms of progression-free survival (PFS), HAIC-FO outperformed anti-VEGF-TKI monotherapy, ICI monotherapy, and several ICI combinations. However, it was not superior to lenvatinib plus TACE or lenvatinib plus pembrolizumab. Based on the Surface Under the Cumulative Ranking Curve (SUCRA) values, HAIC-FO was ranked the most effective in terms of OS (SUCRA = 0.961) and objective response rate (ORR) (SUCRA = 0.971). The results of the subgroup analysis suggested that HAIC-FO achieved the best OS benefit in the macrovascular invasion (MVI) and extrahepatic spread (EHS) subgroup (SUCRA = 0.99) and that tremelimumab combined with durvalumab achieved the best OS benefit in the Asian subgroup (SUCRA = 0.88). Conclusion This systematic review and network meta-analysis suggest that HAIC-based therapies may become a potential first-line treatment option for advanced HCC, especially for patients in Mainland China with MVI and EHS. Additionally, immune-related treatments may be more suitable for Asian populations.
Collapse
Affiliation(s)
- Jingyi Li
- Department of Medical Oncology, the First Hospital of China Medical University, Shenyang, China
- Key Laboratory of Anticancer Drugs and Biotherapy of Liaoning Province, the First Hospital of China Medical University, Shenyang, China
- Liaoning Province Clinical Research Center for Cancer, the First Hospital of China Medical University, Shenyang, China
- Clinical Cancer Treatment and Research Center of Shenyang, the First Hospital of China Medical University, Shenyang, China
| | - Bowen Yang
- Department of Medical Oncology, the First Hospital of China Medical University, Shenyang, China
- Key Laboratory of Anticancer Drugs and Biotherapy of Liaoning Province, the First Hospital of China Medical University, Shenyang, China
- Liaoning Province Clinical Research Center for Cancer, the First Hospital of China Medical University, Shenyang, China
- Clinical Cancer Treatment and Research Center of Shenyang, the First Hospital of China Medical University, Shenyang, China
| | - Zan Teng
- Department of Medical Oncology, the First Hospital of China Medical University, Shenyang, China
- Key Laboratory of Anticancer Drugs and Biotherapy of Liaoning Province, the First Hospital of China Medical University, Shenyang, China
- Liaoning Province Clinical Research Center for Cancer, the First Hospital of China Medical University, Shenyang, China
- Clinical Cancer Treatment and Research Center of Shenyang, the First Hospital of China Medical University, Shenyang, China
| | - Yunpeng Liu
- Department of Medical Oncology, the First Hospital of China Medical University, Shenyang, China
- Key Laboratory of Anticancer Drugs and Biotherapy of Liaoning Province, the First Hospital of China Medical University, Shenyang, China
- Liaoning Province Clinical Research Center for Cancer, the First Hospital of China Medical University, Shenyang, China
- Clinical Cancer Treatment and Research Center of Shenyang, the First Hospital of China Medical University, Shenyang, China
| | - Danni Li
- Department of Medical Oncology, the First Hospital of China Medical University, Shenyang, China
- Key Laboratory of Anticancer Drugs and Biotherapy of Liaoning Province, the First Hospital of China Medical University, Shenyang, China
- Liaoning Province Clinical Research Center for Cancer, the First Hospital of China Medical University, Shenyang, China
- Clinical Cancer Treatment and Research Center of Shenyang, the First Hospital of China Medical University, Shenyang, China
| | - Xiujuan Qu
- Department of Medical Oncology, the First Hospital of China Medical University, Shenyang, China
- Key Laboratory of Anticancer Drugs and Biotherapy of Liaoning Province, the First Hospital of China Medical University, Shenyang, China
- Liaoning Province Clinical Research Center for Cancer, the First Hospital of China Medical University, Shenyang, China
- Clinical Cancer Treatment and Research Center of Shenyang, the First Hospital of China Medical University, Shenyang, China
| |
Collapse
|
|
3
|
Connor Chick R, Ruff SM, Monasterio J, Neilson T, Tsai S, Ejaz A, Tsung A, Kim AC. Implementation of Hepatic Artery Infusion Pump Therapy: Real-World Single-Center Experience. J Surg Oncol 2024. [PMID: 39238425 DOI: 10.1002/jso.27859] [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: 08/14/2024] [Accepted: 08/18/2024] [Indexed: 09/07/2024]
Abstract
BACKGROUND AND OBJECTIVES Hepatic artery infusion pump (HAIP) therapy is an available option at highly specialized centers to treat unresectable liver tumors (e.g., colorectal liver metastases [CRLM]). This study describes the safety and outcomes of HAIP program implementation at an academic-based cancer center. METHODS Patients who underwent HAIP placement (2021-2023) were included. Categorical and continuous variables were compared using Chi-square and Kruska-Wallis tests, respectively. Survival and variables associated with survival were calculated using the Kaplan-Meier method and Cox proportional hazards model, respectively. RESULTS Of the 26 HAIP procedures for unresectable CRLM, four were done as adjuvant therapy. Median duration of HAIP therapy was 9.2 months and four patients subsequently underwent hepatectomy. Complication rate was 37.5%, with biliary complication rate of 23.1%. Median overall survival (OS) from date of diagnosis was 55.2 months. Concurrent primary tumor resection was associated with inferior OS (p = 0.030). Multivariable regression did not identify independent predictors of OS. Progression-free survival from time of HAIP placement was 7.8 months. CONCLUSIONS HAIP placement was technically successful in most patients with an acceptable complication rate. Survival outcomes were comparable with those described in the literature for HAIP therapy in combination with systemic therapy. The significant difference in outcomes for those with concurrent colectomy warrants further investigation.
Collapse
Affiliation(s)
- Robert Connor Chick
- Division of Surgical Oncology, The James Cancer Hospital and Solove Research Institute, The Ohio State University, Columbus, Ohio, USA
| | - Samantha M Ruff
- Division of Surgical Oncology, The James Cancer Hospital and Solove Research Institute, The Ohio State University, Columbus, Ohio, USA
- Department of Surgery, University of Virginia, Charlottesville, Virgina, USA
| | - Julia Monasterio
- College of Medicine, The Ohio State University, Columbus, Ohio, USA
| | - Taylor Neilson
- Department of Surgery, The Ohio State University Wexner Medical Center, Columbus, Ohio, USA
| | - Susan Tsai
- Division of Surgical Oncology, The James Cancer Hospital and Solove Research Institute, The Ohio State University, Columbus, Ohio, USA
| | - Aslam Ejaz
- Department of Surgery, Division of Surgical Oncology, University of Illinois Chicago, Chicago, Illinois, USA
| | - Allan Tsung
- Department of Surgery, University of Virginia, Charlottesville, Virgina, USA
| | - Alex C Kim
- Department of Surgery, Division of Surgical Oncology, University of Texas Southwestern Medical Center, Dallas, Texas, USA
| |
Collapse
|
|
4
|
Meng W, Pan L, Huang L, Li Q, Sun Y. Applications of image-guided locoregional transarterial chemotherapy in patients with inoperable colorectal cancer: a review. Front Oncol 2024; 14:1464242. [PMID: 39246324 PMCID: PMC11377196 DOI: 10.3389/fonc.2024.1464242] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/13/2024] [Accepted: 08/08/2024] [Indexed: 09/10/2024] Open
Abstract
With the development of comprehensive treatment, locoregional transarterial chemotherapy has become an alternative conversion therapy, palliative therapy, and neoadjuvant therapy for many solid malignant tumors. Locoregional transarterial chemotherapy, which is most frequently used for treating liver cancer, has the characteristics of high regional efficacy and few systemic adverse reactions. In recent years, the number of relevant reports of locoregional chemotherapy for treating initially inoperable colorectal cancer (CRC), including non-metastatic and metastatic CRC, has gradually increased. However, the specific treatment options for such locoregional therapy are not the same, and its indications, medication regimens and combined treatments have not reached any consensus. In this review, the application status of locoregional transarterial chemotherapy in primary and metastatic CRC patients has been reviewed and summarized to provide a reference for future clinical work and scientific research.
Collapse
Affiliation(s)
- Wenjun Meng
- Department of Biotherapy, Cancer Center, West China Hospital, Sichuan University, Chengdu, China
- West China School of Medicine, Sichuan University, Chengdu, China
| | - Lu Pan
- Department of Biotherapy, Cancer Center, West China Hospital, Sichuan University, Chengdu, China
- West China School of Nursing, Sichuan University, Chengdu, China
| | - Li Huang
- Department of Biotherapy, Cancer Center, West China Hospital, Sichuan University, Chengdu, China
- West China School of Nursing, Sichuan University, Chengdu, China
| | - Qing Li
- Department of Biotherapy, Cancer Center, West China Hospital, Sichuan University, Chengdu, China
| | - Yi Sun
- Department of Oncology and Hematology, Air Force Hospital of Western Theater Command, Chengdu, China
| |
Collapse
|
|
5
|
Kolbeinsson HM, Chandana S, Wright GP, Chung M. Pancreatic Cancer: A Review of Current Treatment and Novel Therapies. J INVEST SURG 2023; 36:2129884. [PMID: 36191926 DOI: 10.1080/08941939.2022.2129884] [Citation(s) in RCA: 134] [Impact Index Per Article: 67.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/07/2023]
Abstract
Pancreatic cancer is one of the leading causes for cancer-related deaths in the United States. Majority of patients present with unresectable or metastatic disease. For those that present with localized disease, a multidisciplinary approach is necessary to maximize survival and optimize outcomes. The quality and safety of surgery for pancreatic cancer have improved in recent years with increasing adoption of minimally invasive techniques and surgical adjuncts. Systemic chemotherapy has also evolved to impact survival. It is now increasingly being utilized in the neoadjuvant setting, often with concomitant radiation. Increased utilization of genomic testing in metastatic pancreatic cancer has led to better understanding of their biology, thereby allowing clinicians to consider potential targeted therapies. Similarly, targeted agents such as PARP inhibitors and immune checkpoint- inhibitors have emerged with promising results. In summary, pancreatic cancer remains a disease with poor long-term survival. However, recent developments have led to improved outcomes and have changed practice in the past decade. This review summarizes current practices in pancreatic cancer treatment and the milestones that brought us to where we are today, along with emerging therapies.
Collapse
Affiliation(s)
- Hordur Mar Kolbeinsson
- Spectrum Health General Surgery Residency, Grand Rapids, Michigan, USA.,Department of Surgery, Michigan State University College of Human Medicine, Grand Rapids, Michigan, USA
| | - Sreenivasa Chandana
- Department of Surgery, Michigan State University College of Human Medicine, Grand Rapids, Michigan, USA.,Cancer and Hematology Centers of Western Michigan, PC, Grand Rapids, Michigan, USA
| | - G Paul Wright
- Spectrum Health General Surgery Residency, Grand Rapids, Michigan, USA.,Department of Surgery, Michigan State University College of Human Medicine, Grand Rapids, Michigan, USA.,Division of Surgical Oncology, Spectrum Health Medical Group, Grand Rapids, Michigan, USA
| | - Mathew Chung
- Spectrum Health General Surgery Residency, Grand Rapids, Michigan, USA.,Department of Surgery, Michigan State University College of Human Medicine, Grand Rapids, Michigan, USA.,Division of Surgical Oncology, Spectrum Health Medical Group, Grand Rapids, Michigan, USA
| |
Collapse
|
|
6
|
Patel RK, Rahman S, Schwantes IR, Bartlett A, Eil R, Farsad K, Fowler K, Goodyear SM, Hansen L, Kardosh A, Nabavizadeh N, Rocha FG, Tsikitis VL, Wong MH, Mayo SC. Updated Management of Colorectal Cancer Liver Metastases: Scientific Advances Driving Modern Therapeutic Innovations. Cell Mol Gastroenterol Hepatol 2023; 16:881-894. [PMID: 37678799 PMCID: PMC10598050 DOI: 10.1016/j.jcmgh.2023.08.012] [Citation(s) in RCA: 12] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/01/2023] [Revised: 08/30/2023] [Accepted: 08/30/2023] [Indexed: 09/09/2023]
Abstract
Colorectal cancer is the second leading cause of cancer-related deaths in the United States and accounts for an estimated 1 million deaths annually worldwide. The liver is the most common site of metastatic spread from colorectal cancer, significantly driving both morbidity and mortality. Although remarkable advances have been made in recent years in the management for patients with colorectal cancer liver metastases, significant challenges remain in early detection, prevention of progression and recurrence, and in the development of more effective therapeutics. In 2017, our group held a multidisciplinary state-of-the-science symposium to discuss the rapidly evolving clinical and scientific advances in the field of colorectal liver metastases, including novel early detection and prognostic liquid biomarkers, identification of high-risk cohorts, advances in tumor-immune therapy, and different regional and systemic therapeutic strategies. Since that time, there have been scientific discoveries translating into therapeutic innovations addressing the current management challenges. These innovations are currently reshaping the treatment paradigms and spurring further scientific discovery. Herein, we present an updated discussion of both the scientific and clinical advances and future directions in the management of colorectal liver metastases, including adoptive T-cell therapies, novel blood-based biomarkers, and the role of the tumor microbiome. In addition, we provide a comprehensive overview detailing the role of modern multidisciplinary clinical approaches used in the management of patients with colorectal liver metastases, including considerations toward specific molecular tumor profiles identified on next generation sequencing, as well as quality of life implications for these innovative treatments.
Collapse
Affiliation(s)
- Ranish K Patel
- Department of Surgery, Oregon Health & Science University (OHSU), Portland, Oregon
| | - Shahrose Rahman
- Department of Surgery, Oregon Health & Science University (OHSU), Portland, Oregon
| | - Issac R Schwantes
- Department of Surgery, Oregon Health & Science University (OHSU), Portland, Oregon
| | - Alexandra Bartlett
- Division of Surgical Oncology, Department of Surgery, OHSU, Portland, Oregon
| | - Robert Eil
- Division of Surgical Oncology, Department of Surgery, OHSU, Portland, Oregon; The Knight Cancer Institute, OHSU, Portland, Oregon
| | - Khashayar Farsad
- Charles T. Dotter Department of Interventional Radiology, OHSU, Portland, Oregon
| | - Kathryn Fowler
- Department of Surgery, Oregon Health & Science University (OHSU), Portland, Oregon
| | - Shaun M Goodyear
- The Knight Cancer Institute, OHSU, Portland, Oregon; Division of Hematology and Oncology, School of Medicine, OHSU, Portland, Oregon
| | - Lissi Hansen
- The Knight Cancer Institute, OHSU, Portland, Oregon; School of Nursing, OHSU, Portland, Oregon
| | - Adel Kardosh
- The Knight Cancer Institute, OHSU, Portland, Oregon; Division of Hematology and Oncology, School of Medicine, OHSU, Portland, Oregon
| | - Nima Nabavizadeh
- The Knight Cancer Institute, OHSU, Portland, Oregon; Department of Radiation Medicine, OHSU, Portland, Oregon
| | - Flavio G Rocha
- Division of Surgical Oncology, Department of Surgery, OHSU, Portland, Oregon; The Knight Cancer Institute, OHSU, Portland, Oregon
| | - V Liana Tsikitis
- The Knight Cancer Institute, OHSU, Portland, Oregon; Division of Gastrointestinal Surgery, Department of Surgery, OHSU, Portland, Oregon
| | - Melissa H Wong
- The Knight Cancer Institute, OHSU, Portland, Oregon; Department of Cell, Developmental and Cancer Biology, OHSU, Portland, Oregon
| | - Skye C Mayo
- Division of Surgical Oncology, Department of Surgery, OHSU, Portland, Oregon; The Knight Cancer Institute, OHSU, Portland, Oregon.
| |
Collapse
|
|
7
|
Kong SY, Song JJ, Jin YQ, Deng MJ, Yan JX. Hepatic arterial infusion chemotherapy versus transarterial chemoembolization for patients with unresectable hepatocellular carcinoma: a systematic review and meta-analysis. Acta Clin Belg 2023; 78:171-179. [PMID: 35587164 DOI: 10.1080/17843286.2022.2076791] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/24/2022]
Abstract
BACKGROUND We carried out a systematic review and meta-analysis to assess the safety and effectiveness of hepatic arterial infusion chemotherapy (HAIC) compared with transarterial chemoembolization (TACE) for patients with unresectable hepatocellular carcinoma (uHCC). METHODS Eligible studies were searched by MEDLINE, the Cochrane Library, Embase, and Web of Science from January 1995 to January 2022, investigating eligible literature comparing HAIC and TACE for patients with HCC. The main outcome measures included progression-free survival (PFS), overall survival (OS), adverse events (AEs), objective response rate (ORR), and diseases control rate (DCR). RESULTS Eight literature and 1028 patients were enrolled in this meta-analysis. The pooled PFS, OS, ORR, and DCR were HR = 0.89 (95% CI, 0.81-0.98), HR = 0.84 (95% CI, 0.75-0.93), OR = 2.77 (95% CI, 2.01-3.80), and OR = 4.64 (95% CI, 2.40-8.99), respectively. The adverse events of HAIC were lower than TACE. CONCLUSION Our meta-analysis revealed that HAIC can achieve a better effect and survival benefits than TACE in patients with uHCC.
Collapse
Affiliation(s)
- Shun-Yu Kong
- Department of Interventional Therapy, Affiliated Hospital of Qinghai University, Xining, China.,Department of Postgraduate, Qinghai University, Xining, China
| | - Jiao-Jiao Song
- Department of Postgraduate, Qinghai University, Xining, China.,Department of Ultrasound, Qinghai Province Hospital, Xining, China
| | - Yao-Qi Jin
- XiangYa School of Medicine, Central South University, Changsha, China
| | - Man-Jun Deng
- Department of Hepatopancreatobiliary Surgery, Affiliated Hospital of Qinghai University, Xining, China
| | - Jing-Xin Yan
- Department of Interventional Therapy, Affiliated Hospital of Qinghai University, Xining, China.,Department of Postgraduate, Qinghai University, Xining, China
| |
Collapse
|
|
8
|
Liu J, Zhang J, Wang Y, Shu G, Lou C, Du Z. HAIC versus TACE for patients with unresectable hepatocellular carcinoma: A systematic review and meta-analysis. Medicine (Baltimore) 2022; 101:e32390. [PMID: 36595819 PMCID: PMC9794325 DOI: 10.1097/md.0000000000032390] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/13/2022] [Accepted: 12/02/2022] [Indexed: 12/28/2022] Open
Abstract
BACKGROUND Hepatic arterial infusion chemotherapy (HAIC) and Transarterial chemoembolization (TACE) both showed good local efficacy in advanced or unresectable hepatocellular carcinoma (HCC). We performed a systematic review and meta-analysis to compare the effect of HAIC with TACE in patients with unresectable HCC. METHODS Clinical trials, which were about HAIC or TACE in Patients with unresectable HCC, were identified by searching PubMed, Medline, and EMBASE from January 2010 to March 2022. A meta-analysis was performed to analyze HAIC in comparison with TACE. Treatment response, 1-year overall survival (OS), 2-year OS and serious adverse events were evaluated in this meta-analysis. RESULTS This meta-analysis included 6 studies. Objective response rate or Partial response in the HAIC group was significantly more than that in the TACE group (P < .05). But, stable disease showed no difference between the 2 groups (P = .52). Disease control rate in the HAIC group was better than that in the TACE group (P < .05). Progressive disease in the HAIC group was less than that in the TACE group (P < .05). In 1-year OS, there was no significant deterioration between the 2 groups (P = .53). There was not significant difference in 2-year OS between the 2 groups (P = .05). serious adverse events in the HAIC group was significantly less than that in the TACE group (P < .05). CONCLUSION To some degree, HAIC may be a better therapeutic method in patients with unresectable HCC than TACE.
Collapse
Affiliation(s)
- Junguo Liu
- The Third Central Hospital of Tianjin (The Third Central Clinical College of Tianjin Medical University), Tianjin Institute of Hepatobiliary Disease, Tianjin Key Laboratory of Extracorporeal Life Support for Critical Diseases, Artificial Cell Engineering Technology Research Center, Tianjin, China
| | - Jinjuan Zhang
- The Third Central Hospital of Tianjin (The Third Central Clinical College of Tianjin Medical University), Tianjin Institute of Hepatobiliary Disease, Tianjin Key Laboratory of Extracorporeal Life Support for Critical Diseases, Artificial Cell Engineering Technology Research Center, Tianjin, China
| | - Yijun Wang
- The Third Central Hospital of Tianjin (The Third Central Clinical College of Tianjin Medical University), Tianjin Institute of Hepatobiliary Disease, Tianjin Key Laboratory of Extracorporeal Life Support for Critical Diseases, Artificial Cell Engineering Technology Research Center, Tianjin, China
| | - Guiming Shu
- The Third Central Hospital of Tianjin (The Third Central Clinical College of Tianjin Medical University), Tianjin Institute of Hepatobiliary Disease, Tianjin Key Laboratory of Extracorporeal Life Support for Critical Diseases, Artificial Cell Engineering Technology Research Center, Tianjin, China
| | - Cheng Lou
- The Third Central Hospital of Tianjin (The Third Central Clinical College of Tianjin Medical University), Tianjin Institute of Hepatobiliary Disease, Tianjin Key Laboratory of Extracorporeal Life Support for Critical Diseases, Artificial Cell Engineering Technology Research Center, Tianjin, China
| | - Zhi Du
- The Third Central Hospital of Tianjin (The Third Central Clinical College of Tianjin Medical University), Tianjin Institute of Hepatobiliary Disease, Tianjin Key Laboratory of Extracorporeal Life Support for Critical Diseases, Artificial Cell Engineering Technology Research Center, Tianjin, China
| |
Collapse
|
|
9
|
Walker BS, Billingsley KG, Sutton TL, Kolbeck KJ, Korngold EK, Nabavizadeh N, Dewey EN, Herzig DO, Lopez CD, Mayo SC. Hepatic arterial infusion pump chemotherapy combined with systemic therapy for patients with advanced colorectal liver metastases: Outcomes in a newly established program. J Surg Oncol 2022; 126:513-522. [PMID: 35522249 DOI: 10.1002/jso.26911] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/27/2022] [Revised: 04/22/2022] [Accepted: 04/23/2022] [Indexed: 11/07/2022]
Abstract
BACKGROUND AND OBJECTIVES Colorectal liver metastasis (CRLM) is a leading cause of morbidity and mortality in patients with colorectal cancer. Hepatic arterial infusion (HAI) chemotherapy has been demonstrated to improve survival in patients with resected CRLM and to facilitate conversion of technically unresectable disease. METHODS Between 2016 and 2018, n = 22 HAI pumps were placed for CRLM. All patients received systemic chemotherapy concurrently with HAI floxuridine/dexamethasone. Overall survival (OS) and progression-free survival (PFS) were assessed using the Kaplan-Meier method. RESULTS HAI pumps were placed in seven patients with completely resected CRLM and 15 patients with unresectable disease. Twenty-one patients received HAI floxuridine with a median of 5 total HAI cycles (interquartile range: 4-7). Biliary sclerosis was the most common HAI-related complication (n = 5, 24%). Of the 13 patients treated to convert unresectable CRLM, 3 (23%) underwent hepatic resection with curative intent after a median of 7 HAI cycles (range: 4-10). For all HAI patients, the mean OS was 26.7 months from CRLM diagnosis, while the median PFS and hepatic PFS from pump placement were 9 and 13 months, respectively. CONCLUSION Concomitant HAI and systemic therapy can be utilized at multidisciplinary programs for patients with advanced CRLM, both in the adjuvant setting and to facilitate conversion of unresectable disease.
Collapse
Affiliation(s)
- Brett S Walker
- Oregon Health & Science University (OHSU), Department of Surgery, Division of Surgical Oncology, Knight Cancer Institute, Portland, Oregon, USA
| | | | - Thomas L Sutton
- Oregon Health & Science University (OHSU), Department of Surgery, Division of Surgical Oncology, Knight Cancer Institute, Portland, Oregon, USA
| | - Kenneth J Kolbeck
- OHSU, Department of Interventional Radiology, Dotter Institute, Portland, Oregon, USA
| | | | | | | | - Daniel O Herzig
- OHSU, Division of Colorectal Surgery, Department of Surgery, Portland, Oregon, USA
| | - Charles D Lopez
- OHSU, Division of Hematology and Medical Oncology, Department of Medicine, Portland, Oregon, USA.,The Knight Cancer Institute at OHSU, Portland, Oregon, USA
| | - Skye C Mayo
- Oregon Health & Science University (OHSU), Department of Surgery, Division of Surgical Oncology, Knight Cancer Institute, Portland, Oregon, USA.,The Knight Cancer Institute at OHSU, Portland, Oregon, USA
| |
Collapse
|
|
10
|
Cai Z, He C, Zhao C, Lin X. Survival Comparisons of Hepatic Arterial Infusion Chemotherapy With mFOLFOX and Transarterial Chemoembolization in Patients With Unresectable Intrahepatic Cholangiocarcinoma. Front Oncol 2021; 11:611118. [PMID: 33868997 PMCID: PMC8047640 DOI: 10.3389/fonc.2021.611118] [Citation(s) in RCA: 14] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/28/2020] [Accepted: 03/18/2021] [Indexed: 12/30/2022] Open
Abstract
Background Intrahepatic cholangiocarcinoma (ICC) has a poor prognosis and 40%-60% of patients present with advanced disease at the time of diagnosis. Transarterial chemoembolization (TACE) and hepatic arterial infusion chemotherapy (HAIC) have recently been used in unresectable ICC. The aim of this study was to compare the survival differences of unresectable ICC patients after TACE and HAIC treatment. Methods Between March 2011 and October 2019, a total of 126 patients with unresectable ICC, as evident from biopsies and imaging, and who had received TACE or HAIC were enrolled in this study. Baseline characteristics and survival differences were compared between the TACE and HAIC treatment groups. Results ICC Patients had significantly higher survival rates after the HAIC treatment, compared with those after TACE treatment [1-year overall survival (OS) rates: 60.2% vs. 42.9%, 2-year OS rates: 38.7% vs. 29.4%, P=0.028; 1-year progression-free survival (PFS) rates: 15.0% vs. 20.0%, 2-year PFS rates: 0% vs. 0%, P=0.641; 1-year only intrahepatic PFS (OIPFS) rates: 35.0% vs. 24.4%, 2-year OIPFS rates: 13.1% vs. 14.6%, P = 0.026]. Multivariate Cox regression analysis showed that HAIC was a significant and independent factor for OS and OIPFS in the study cohort. Conclusions HAIC is superior to TACE for treatment of unresectable ICC. A new tumor response evaluation procedure for HAIC treatment in unresectable ICC patients is needed to provide better therapeutic strategies. A randomized clinical trial comparing the survival benefits of HAIC and TACE is therefore being considered.
Collapse
Affiliation(s)
- Zhiyuan Cai
- Department of Pancreatobiliary Surgery, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou, China.,Guangdong Provincial Engineering Research Center of Molecular Imaging, The Fifth Affiliated Hospital of Sun Yat-sen University, Zhuhai, China
| | - Chaobin He
- Department of Pancreatobiliary Surgery, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou, China
| | - Chongyu Zhao
- Department of Pancreatobiliary Surgery, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou, China
| | - Xiaojun Lin
- Department of Pancreatobiliary Surgery, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou, China
| |
Collapse
|
|
11
|
Ouyang G, Pan G, Xu H, Wu Y, Liu Z, Lu W, Yi B, Chen X. Sorafenib Plus Hepatic Arterial Infusion Chemotherapy in Advanced Hepatocellular Carcinoma: A Systematic Review and Meta-Analysis. J Clin Gastroenterol 2020; 54:675-681. [PMID: 32569032 DOI: 10.1097/mcg.0000000000001384] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/20/2023]
Abstract
BACKGROUND AND AIM The clinical utility of sorafenib plus hepatic arterial infusion chemotherapy (SoraHAIC) in advanced hepatocellular carcinoma (HCC) patients remains unclear. We, therefore, conducted the current meta-analysis to systematically evaluate the efficacy and safety of SoraHAIC therapy on major outcomes with advanced HCC patients. METHODS A systematic search of The Cochrane Library, PubMed, and Embase databases was performed. The major outcomes in patients with advanced HCC were divided into SoraHAIC group and sorafenib group, which included overall response rate, overall survival, progressive disease, and adverse events. RESULTS Involving a total of 726 patients from 5 included studies, our meta-analysis demonstrated that SoraHAIC showed significantly more improvement than sorafenib alone in overall response rate [risk ratio=3.08; 95% confidence interval (CI), 1.38-6.89; P=0.006] and complete response (risk ratio=5.84; 95% CI, 1.85-18.45; P=0.003). With regard to survival outcome, the combination therapy also significantly prolongs the median overall survival than sorafenib monotherapy (hazard ratio=0.59; 95% CI, 0.35-1.00; P=0.05). In addition, the risk of adverse events such as anemia, neutropenia, and thrombocytopenia was significantly greater in the combination group than in the sorafenib group (P<0.05 for all). CONCLUSIONS This meta-analysis indicated that SoraHAIC seems to be efficient and safe for advanced HCC patients. However, additional large-scale randomized controlled trials are needed to further investigate the clinical benefit.
Collapse
Affiliation(s)
- Guoqing Ouyang
- Department of Hepatobiliary Surgery, Liuzhou People's Hospital, Liuzhou, Guangxi
| | - Guangdong Pan
- Department of Hepatobiliary Surgery, Liuzhou People's Hospital, Liuzhou, Guangxi
| | - Honglai Xu
- Department of Hepatobiliary Surgery, Liuzhou People's Hospital, Liuzhou, Guangxi
| | - Yongrong Wu
- Department of Hepatobiliary Surgery, Liuzhou People's Hospital, Liuzhou, Guangxi
| | - Zhen Liu
- Department of Hepatobiliary Surgery, Liuzhou People's Hospital, Liuzhou, Guangxi
| | - Wuhang Lu
- Department of Hepatobiliary Surgery, Liuzhou People's Hospital, Liuzhou, Guangxi
| | - Bin Yi
- Department of Cardiothoracic Surgery, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong
| | - Xiang Chen
- Department of General Surgery, The Second Xiangya Hospital, Central South University, Changsha, Hunan, China
| |
Collapse
|
|
12
|
Wang Y, Li J, Subramaniyan I, do Vale GD, Chaudhary J, Anwar A, Wight-Carter M, McDonald JG, Putnam WC, Qin T, Zhang H, Corbin IR. An implanted port-catheter system for repeated hepatic arterial infusion of low-density lipoprotein-docosahexaenoic acid nanoparticles in normal rats: A safety study. Toxicol Appl Pharmacol 2020; 400:115037. [PMID: 32417438 DOI: 10.1016/j.taap.2020.115037] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/24/2019] [Revised: 04/27/2020] [Accepted: 05/09/2020] [Indexed: 11/25/2022]
Abstract
BACKGROUND In recent years, small animal arterial port-catheter systems have been implemented in rodents with reasonable success. The aim of the current study is to employ the small animal port-catheter system to evaluate the safety of multiple hepatic-artery infusions (HAI) of low-density lipoprotein-docosahexaenoic acid (LDL-DHA) nanoparticles to the rat liver. METHODS Wistar rats underwent surgical placement of indwelling HAI ports. Repeated administrations of PBS or LDL-DHA nanoparticles were performed through the port at baseline and days 3 and 6. Rats were sacrificed on day 9 at which point blood and various organs were collected for histopathology and biochemical analyses. RESULTS The port-catheter systems were implanted successfully and repeated infusions of PBS or LDL-DHA nanoparticles were tolerated well by all animals over the duration of the study. Measurements of serum liver/renal function tests, glucose and lipid levels did not differ between control and LDL-DHA treated rats. The liver histology was unremarkable in the LDL-DHA treated rats and the expression of hepatic inflammatory regulators (NF-κβ, IL-6 and CRP) were similar to control rats. Repeated infusions of LDL-DHA nanoparticles did not alter liver glutathione content or the lipid profile in the treated rats. The DHA extracted by the liver was preferentially metabolized to the anti-inflammatory DHA-derived mediator, protectin DX. CONCLUSION Our findings indicate that repeated HAI of LDL-DHA nanoparticles is not only well tolerated and safe in the rat, but may also be protective to the liver.
Collapse
Affiliation(s)
- Yuzhu Wang
- Department of Hepatobiliary and pancreatic surgery, Henan Provincial People's Hospital, Zhengzhou University People's Hospital, Henan University People's Hospital, Zhengzhou, Henan 450003, China; Advanced Imaging Research Center, University of Texas Southwestern Medical Center at Dallas, Dallas, TX 75390, USA
| | - Junjie Li
- Advanced Imaging Research Center, University of Texas Southwestern Medical Center at Dallas, Dallas, TX 75390, USA
| | - Indhumathy Subramaniyan
- Department of Pharmaceutical Sciences, Department of Pharmacy Practice within the Jerry H. Hodge School of Pharmacy, Texas Tech University Health Sciences Center, Dallas, TX 75235, USA
| | | | - Jaideep Chaudhary
- Advanced Imaging Research Center, University of Texas Southwestern Medical Center at Dallas, Dallas, TX 75390, USA
| | - Arnida Anwar
- Advanced Imaging Research Center, University of Texas Southwestern Medical Center at Dallas, Dallas, TX 75390, USA
| | | | | | - William C Putnam
- Department of Pharmaceutical Sciences, Department of Pharmacy Practice within the Jerry H. Hodge School of Pharmacy, Texas Tech University Health Sciences Center, Dallas, TX 75235, USA
| | - Tao Qin
- Department of Hepatobiliary and pancreatic surgery, Henan Provincial People's Hospital, Zhengzhou University People's Hospital, Henan University People's Hospital, Zhengzhou, Henan 450003, China
| | - Hongwei Zhang
- Department of Hepatobiliary and pancreatic surgery, Henan Provincial People's Hospital, Zhengzhou University People's Hospital, Henan University People's Hospital, Zhengzhou, Henan 450003, China
| | - Ian R Corbin
- Advanced Imaging Research Center, University of Texas Southwestern Medical Center at Dallas, Dallas, TX 75390, USA; Internal Medicine Division of Liver and Digestive Diseases, Dallas, TX 75390, USA; RadiologyUniversity of Texas Southwestern Medical Center at Dallas, Dallas, TX 75390, USA.
| |
Collapse
|
|
13
|
Fluoropyrimidine Modulation of the Anti-Tumor Immune Response-Prospects for Improved Colorectal Cancer Treatment. Cancers (Basel) 2020; 12:cancers12061641. [PMID: 32575843 PMCID: PMC7352193 DOI: 10.3390/cancers12061641] [Citation(s) in RCA: 20] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/25/2020] [Revised: 06/18/2020] [Accepted: 06/19/2020] [Indexed: 02/07/2023] Open
Abstract
Chemotherapy modulates the anti-tumor immune response and outcomes depend on the balance of favorable and unfavorable effects of drugs on anti-tumor immunity. 5-Florouracil (5-FU) is widely used in adjuvant chemotherapy regimens to treat colorectal cancer (CRC) and provides a survival benefit. However, survival remains poor for CRC patients with advanced and metastatic disease and immune checkpoint blockade therapy benefits only a sub-set of CRC patients. Here we discuss the effects of 5-FU-based chemotherapy regimens to the anti-tumor immune response. We consider how different aspects of 5-FU's multi-factorial mechanism differentially affect malignant and immune cell populations. We summarize recent studies with polymeric fluoropyrimidines (e.g., F10, CF10) that enhance DNA-directed effects and discuss how such approaches may be used to enhance the anti-tumor immune response and improve outcomes.
Collapse
|
|
14
|
Johnson BW, Wright GP. Regional therapies for the treatment of primary and metastatic hepatic tumors: A disease-based review of techniques and critical appraisal of current evidence. Am J Surg 2018; 217:541-545. [PMID: 30782316 DOI: 10.1016/j.amjsurg.2018.10.018] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/01/2018] [Revised: 10/05/2018] [Accepted: 10/09/2018] [Indexed: 12/24/2022]
Abstract
The practice of hepatic surgery has become increasingly complex as additional therapeutic options emerge to treat both primary and metastatic tumors of the liver. Liver-directed therapy options include selective internal radiation therapy (SIRT), stereotactic body radiation therapy, chemoembolization, bland embolization, hepatic artery infusion chemotherapy (HAIC), and ablative techniques such as microwave or radiofrequency ablation. Hepatocellular carcinoma has been treated with many of these therapies for palliation of symptoms, definitive treatment, and as a bridge to transplantation. Intrahepatic cholangiocarcinoma, particularly patients with unresectable disease, have demonstrated clinical responses to both SIRT as well as HAIC. Colorectal liver metastases have been treated with all of these techniques with varying degrees of success depending on the clinical scenario. A detailed understanding of these technologies and the evidence supporting their use is essential for the modern hepatic surgeon to properly sequence therapies and provide salvage options when first-line treatment has failed. This review describes these techniques and their appropriate usage based on the disease of interest and the respective evidence currently available.
Collapse
Affiliation(s)
- Benjamin W Johnson
- Spectrum Health General Surgery Residency Program, Grand Rapids, MI, USA; Michigan State University College of Human Medicine, Department of Surgery, Grand Rapids, MI, USA
| | - G Paul Wright
- Spectrum Health General Surgery Residency Program, Grand Rapids, MI, USA; Michigan State University College of Human Medicine, Department of Surgery, Grand Rapids, MI, USA; Spectrum Health Medical Group, Division of Surgical Oncology, Grand Rapids, MI, USA.
| |
Collapse
|
|
15
|
Transarterial chemoembolization with raltitrexed-based or floxuridine-based chemotherapy for unresectable colorectal cancer liver metastasis. Clin Transl Oncol 2018; 21:443-450. [PMID: 30306400 DOI: 10.1007/s12094-018-1942-0] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/29/2018] [Accepted: 09/02/2018] [Indexed: 12/22/2022]
Abstract
PURPOSE To evaluate and compare the efficiency and safety of raltitrexed- or floxuridine (FUDR)-based transarterial chemoembolization (TACE) in patients with unresectable colorectal cancer liver metastasis (CRCLM). METHODS We conducted a retrospective analysis of 81 patients with unresectable CRCLM who failed systemic chemotherapy and were treated with TACE in our department from Oct 2014 to Oct 2017. Of these, 61 patients received TACE using raltitrexed, oxaliplatin, and pirarubicin (raltitrexed group), and 20 received TACE using FUDR, oxaliplatin, and pirarubicin (FUDR group). The objective response rate (ORR), disease control rate (DCR), overall survival (OS, from the first TACE), progression-free survival (PFS, from the first TACE), and adverse reactions were evaluated and compared between the two groups, and prognostic factors for OS were analyzed. RESULTS The ORRs of the raltitrexed group and FUDR group were 67.2 and 45.0%, respectively (P = 0.076), and the DCRs were 86.9 and 80.0%, respectively (P = 0.452). The median OS (from first TACE) was 14.0 months in the raltitrexed group and 13.0 months in the FUDR group (P = 0.556). The median PFS (from first TACE) was 2.1 months in the raltitrexed group and 2.4 months in the FUDR group (P = 0.878). Univariate and multivariate analyses showed that the primary tumor site, Child-Pugh class, and combination with local ablation (RFA or CRA) were independent significant factors affecting survival. There were no significant differences in adverse reactions between the two groups (P > 0.05), and no treatment-related death occurred in either group. CONCLUSION TACE treatment based on raltitrexed or FUDR is an efficient and safe alternative choice for treating unresectable CRCLM.
Collapse
|
|
16
|
Italiano D. Hepatic Arterial Infusion Pump: Complications and Nursing Management Regarding Use in Patients With Colorectal Cancer. Clin J Oncol Nurs 2018; 22:340-346. [PMID: 29781463 DOI: 10.1188/18.cjon.340-346] [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: 11/17/2022]
Abstract
BACKGROUND The hepatic arterial infusion (HAI) pump is a treatment-delivery method based on the principle of targeting the tumor site directly and can be used alone or in combination with systemic chemotherapy. OBJECTIVES The intent of this article is to serve as a resource for oncology nurses to safely identify and manage HAI pump complications. These complications include seroma, flipped HAI pump, infection, changes in pressure and temperature, challenging access, dry pump, high residual volume, chemical hepatitis, risk of ulcer, and radiologic imaging considerations. METHODS The authors performed a literature review to provide a foundation for nurses to be able to manage HAI pump infusions. FINDINGS The literature review revealed minimal nursing resources to manage complications with an HAI pump. Resources to manage complications are crucial for safely administering medications and properly maintaining the function of the pump. Attention to patient education should be incorporated in nursing practice.
Collapse
|
|
17
|
Lane RJ, Khin NY, Pavlakis N, Hugh TJ, Clarke SJ, Magnussen J, Rogan C, Flekser RL. Challenges in chemotherapy delivery: comparison of standard chemotherapy delivery to locoregional vascular mass fluid transfer. Future Oncol 2018. [PMID: 29513086 DOI: 10.2217/fon-2017-0546] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/19/2023] Open
Abstract
Standard intravenous chemotherapy delivery to neoplasms relies on simple diffusion gradients from the intravascular to the interstitial space. Systemic perfusion creates untoward effects on normal tissue limiting both concentration and exposure times. Regional intra-arterial therapy is limited by drug recirculation and vascular isolation repeatability and does not address the interstitial microenvironment. Barriers to delivery relate to chaotic vascular architecture, heterogeneous fluid flux, increased interstitial and variable solid tumor pressure and ischemia. To address these difficulties, a delivery system was developed allowing mass fluid transfer of chemotherapeutic agents into the interstitium. This implantable, reusable system is comprised of multiple independently steerable balloons and catheters capable of controlling the locoregional hydraulic and oncotic forces across the vascular endothelium.
Collapse
Affiliation(s)
- Rodney J Lane
- Department of Vascular Research, Macquarie University Hospital, NSW, Sydney, Australia.,Faculty of Medicine & Health Sciences, Macquarie University, NSW, Sydney, Australia.,Department of Surgery, Royal North Shore Hospital, NSW, Sydney, Australia
| | - Nyan Y Khin
- Faculty of Medicine & Health Sciences, Macquarie University, NSW, Sydney, Australia.,AllVascular Pty Ltd, 130-134 Pacific Hwy, St Leonards, NSW 2065, Sydney, Australia
| | - Nick Pavlakis
- Department of Medical Oncology, Royal North Shore Hospital, NSW, Sydney, Australia
| | - Thomas J Hugh
- Department of Surgery, Royal North Shore Hospital, NSW, Sydney, Australia
| | - Stephen J Clarke
- Department of Medical Oncology, Royal North Shore Hospital, NSW, Sydney, Australia
| | - John Magnussen
- Faculty of Medicine & Health Sciences, Macquarie University, NSW, Sydney, Australia
| | - Chris Rogan
- Department of Radiology, Royal Prince Alfred Hospital, NSW, Sydney, Australia
| | - Roger L Flekser
- AllVascular Pty Ltd, 130-134 Pacific Hwy, St Leonards, NSW 2065, Sydney, Australia
| |
Collapse
|
|
18
|
Lévi F, Karaboué A, Etienne-Grimaldi MC, Paintaud G, Focan C, Innominato P, Bouchahda M, Milano G, Chatelut E. Pharmacokinetics of Irinotecan, Oxaliplatin and 5-Fluorouracil During Hepatic Artery Chronomodulated Infusion: A Translational European OPTILIV Study. Clin Pharmacokinet 2017; 56:165-177. [PMID: 27393140 DOI: 10.1007/s40262-016-0431-2] [Citation(s) in RCA: 16] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/12/2023]
Abstract
The combination of hepatic artery infusion (HAI) of irinotecan, 5-fluorouracil and oxaliplatin with intravenous cetuximab has safely achieved prolonged survival in colorectal cancer patients with extensive liver metastases and prior treatment. Systemic exposure to the drugs or their main metabolites was determined during the first course of chronomodulated triplet HAI in 11 patients and related to toxicities after one or three courses. Consistent trends were found between the area under the plasma concentration-time curve (AUC) values of irinotecan, 7-ethyl-10-hydroxycamptothecin (SN38; a bioactive metabolite), total oxaliplatin and platinum ultrafiltrate (P-UF), on the one hand, and subsequent leukopenia severity, on the other hand. Moreover, the maximum plasma concentration (C max) and the AUC of P-UF significantly predicted grades of diarrhoea (p = 0.004 and 0.017, respectively) and anaemia (p = 0.001 and 0.008, respectively) after the first course. Systemic drug exposure helps explain both the adverse events and the low rate of extrahepatic progression-a usual drawback of HAI chemotherapy-thus supporting upfront testing of the regimen. Systems optimization of chronomodulated HAI delivery could further reduce adverse events.
Collapse
Affiliation(s)
- Francis Lévi
- INSERM, UMRS 935, Team «Cancer Chronotherapy and Postoperative Liver Function», Campus CNRS, 7 rue Guy Môquet, Villejuif, France.
- Assistance Publique-Hopitaux de Paris, Medical Oncology Department, Hepatobiliary Centre, and Radiology Department, Paul Brousse Hospital, 14 avenue Paul Vaillant Couturier, Villejuif, France.
- Cancer Chronotherapy Unit, Warwick Medical School, University of Warwick, Gibbett Hill Road, Coventry, CV4 7AL, UK.
| | - Abdoulaye Karaboué
- INSERM, UMRS 935, Team «Cancer Chronotherapy and Postoperative Liver Function», Campus CNRS, 7 rue Guy Môquet, Villejuif, France
- AK-SCIENCE, Research and Therapeutic Innovation, Vitry-sur-Seine, France
| | | | - Gilles Paintaud
- Université François-Rabelais de Tours, CNRS, GICC UMR 7292, CHRU de Tours, Service de Pharmacologie-Toxicologie, Tours, France
| | - Christian Focan
- Department of Oncology, Centre Hospitalier Chrétien, Clinique Saint-Joseph, Liège, Belgium
| | - Pasquale Innominato
- INSERM, UMRS 935, Team «Cancer Chronotherapy and Postoperative Liver Function», Campus CNRS, 7 rue Guy Môquet, Villejuif, France
- Assistance Publique-Hopitaux de Paris, Medical Oncology Department, Hepatobiliary Centre, and Radiology Department, Paul Brousse Hospital, 14 avenue Paul Vaillant Couturier, Villejuif, France
- Cancer Chronotherapy Unit, Warwick Medical School, University of Warwick, Gibbett Hill Road, Coventry, CV4 7AL, UK
| | - Mohamed Bouchahda
- INSERM, UMRS 935, Team «Cancer Chronotherapy and Postoperative Liver Function», Campus CNRS, 7 rue Guy Môquet, Villejuif, France
- Assistance Publique-Hopitaux de Paris, Medical Oncology Department, Hepatobiliary Centre, and Radiology Department, Paul Brousse Hospital, 14 avenue Paul Vaillant Couturier, Villejuif, France
| | - Gérard Milano
- Laboratory of Oncopharmacology, Antoine Lacassagne Centre, Nice, France
| | - Etienne Chatelut
- Institut Claudius-Regaud, CRCT, Université de Toulouse, Inserm, UPS, Toulouse, France
| |
Collapse
|
|
19
|
He MK, Le Y, Li QJ, Yu ZS, Li SH, Wei W, Guo RP, Shi M. Hepatic artery infusion chemotherapy using mFOLFOX versus transarterial chemoembolization for massive unresectable hepatocellular carcinoma: a prospective non-randomized study. CHINESE JOURNAL OF CANCER 2017; 36:83. [PMID: 29061175 PMCID: PMC5654007 DOI: 10.1186/s40880-017-0251-2] [Citation(s) in RCA: 95] [Impact Index Per Article: 11.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 02/17/2017] [Accepted: 05/13/2017] [Indexed: 12/13/2022]
Abstract
BACKGROUND Transarterial chemoembolization (TACE) is recommended as the standard care for unresectable hepatocellular carcinoma (HCC) at Barcelona Clinic Liver Cancer (BCLC) stage A-B. However, the efficacy of TACE on large (≥ 10 cm) stage A-B HCC is far from satisfactory, and it is proposed that hepatic artery infusion chemotherapy (HAIC) might be a better first-line treatment of this disease. Hence, we compared the safety and efficacy of HAIC with the modified FOLFOX (mFOLFOX) regimen and those of TACE in patients with massive unresectable HCC. METHODS A prospective, non-randomized, phase II study was conducted on patients with massive unresectable HCC. The protocol involved HAIC with the mFOLFOX regimen (oxaliplatin, 85 mg/m2 intra-arterial infusion; leucovorin, 400 mg/m2 intra-arterial infusion; and fluorouracil, 400 mg/m2 bolus infusion and 2400 mg/m2 continuous infusion) every 3 weeks and TACE with 50 mg of epirubicin, 50 mg of lobaplatin, 6 mg of mitomycin, and lipiodol and polyvinyl alcohol particles. The tumor responses, time-to-progression (TTP), and safety were assessed. RESULTS A total of 79 patients were recruited for this study: 38 in the HAIC group and 41 in the TACE group. The HAIC group exhibited higher partial response and disease control rates than did the TACE group (52.6% vs. 9.8%, P < 0.001; 83.8% vs. 52.5%, P = 0.004). The median TTPs for the HAIC and TACE groups were 5.87 and 3.6 months (hazard radio [HR] = 2.35, 95% confidence interval [CI] = 1.16-4.76, P = 0.015). More patients in the HAIC group than in the TACE group underwent resection (10 vs. 3, P = 0.033). The proportions of grade 3-4 adverse events (AE) and serious adverse events (SAE) were lower in the HAIC group than in the TACE group (grade 3-4 AEs: 13 vs. 27, P = 0.007; SAEs: 6 vs. 15, P = 0.044). More patients in the TACE group than in the HAIC group had the study treatment terminated early due to intolerable treatment-related adverse events or the withdrawal of consent (10 vs. 2, P = 0.026). CONCLUSIONS HAIC with mFOLFOX yielded significantly better treatment responses and less serious toxicity than did TACE. HAIC might represent a feasible and promising first-line treatment for patients with massive unresectable HCC.
Collapse
Affiliation(s)
- Min-Ke He
- Department of Hepatobiliary Oncology, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, 651 Dongfeng Road East, Guangzhou, 510060, Guangdong, P. R. China
| | - Yong Le
- Department of Hepatobiliary Oncology, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, 651 Dongfeng Road East, Guangzhou, 510060, Guangdong, P. R. China
| | - Qi-Jiong Li
- Department of Hepatobiliary Oncology, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, 651 Dongfeng Road East, Guangzhou, 510060, Guangdong, P. R. China
| | - Zi-Shan Yu
- Department of Hepatobiliary Oncology, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, 651 Dongfeng Road East, Guangzhou, 510060, Guangdong, P. R. China
| | - Shao-Hua Li
- Department of Hepatobiliary Oncology, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, 651 Dongfeng Road East, Guangzhou, 510060, Guangdong, P. R. China
| | - Wei Wei
- Department of Hepatobiliary Oncology, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, 651 Dongfeng Road East, Guangzhou, 510060, Guangdong, P. R. China
| | - Rong-Ping Guo
- Department of Hepatobiliary Oncology, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, 651 Dongfeng Road East, Guangzhou, 510060, Guangdong, P. R. China
| | - Ming Shi
- Department of Hepatobiliary Oncology, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, 651 Dongfeng Road East, Guangzhou, 510060, Guangdong, P. R. China.
| |
Collapse
|
|
20
|
Dervenis C, Xynos E, Sotiropoulos G, Gouvas N, Boukovinas I, Agalianos C, Androulakis N, Athanasiadis A, Christodoulou C, Chrysou E, Emmanouilidis C, Georgiou P, Karachaliou N, Katopodi O, Kountourakis P, Kyriazanos I, Makatsoris T, Papakostas P, Papamichael D, Pechlivanides G, Pentheroudakis G, Pilpilidis I, Sgouros J, Tekkis P, Triantopoulou C, Tzardi M, Vassiliou V, Vini L, Xynogalos S, Ziras N, Souglakos J. Clinical practice guidelines for the management of metastatic colorectal cancer: a consensus statement of the Hellenic Society of Medical Oncologists (HeSMO). Ann Gastroenterol 2016; 29:390-416. [PMID: 27708505 PMCID: PMC5049546 DOI: 10.20524/aog.2016.0050] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/29/2015] [Accepted: 03/10/2016] [Indexed: 12/12/2022] Open
Abstract
There is discrepancy and failure to adhere to current international guidelines for the management of metastatic colorectal cancer (CRC) in hospitals in Greece and Cyprus. The aim of the present document is to provide a consensus on the multidisciplinary management of metastastic CRC, considering both special characteristics of our Healthcare System and international guidelines. Following discussion and online communication among the members of an executive team chosen by the Hellenic Society of Medical Oncology (HeSMO), a consensus for metastastic CRC disease was developed. Statements were subjected to the Delphi methodology on two voting rounds by invited multidisciplinary international experts on CRC. Statements reaching level of agreement by ≥80% were considered as having achieved large consensus, whereas statements reaching 60-80% moderate consensus. One hundred and nine statements were developed. Ninety experts voted for those statements. The median rate of abstain per statement was 18.5% (range: 0-54%). In the end of the process, all statements achieved a large consensus. The importance of centralization, care by a multidisciplinary team, adherence to guidelines, and personalization is emphasized. R0 resection is the only intervention that may offer substantial improvement in the oncological outcomes.
Collapse
Affiliation(s)
- Christos Dervenis
- General Surgery, "Konstantopouleio" Hospital of Athens, Greece (Christos Dervenis)
| | - Evaghelos Xynos
- General Surgery, "InterClinic" Hospital of Heraklion, Greece (Evangelos Xynos)
| | | | - Nikolaos Gouvas
- General Surgery, "METROPOLITAN" Hospital of Piraeus, Greece (Nikolaos Gouvas)
| | - Ioannis Boukovinas
- Medical Oncology, "Bioclinic" of Thessaloniki, Greece (Ioannis Boukovinas)
| | - Christos Agalianos
- General Surgery, Athens Naval & Veterans Hospital, Greece (Christos Agalianos, Ioannis Kyriazanos, George Pechlivanides)
| | - Nikolaos Androulakis
- Medical Oncology, "Venizeleion" Hospital of Heraklion, Greece (Nikolaos Androulakis)
| | | | | | - Evangelia Chrysou
- Radiology, University Hospital of Heraklion, Greece (Evangelia Chrysou)
| | - Christos Emmanouilidis
- Medical Oncology, "Interbalkan" Medical Center, Thessaloniki, Greece (Christos Emmanoulidis)
| | - Panagiotis Georgiou
- Colorectal Surgery, Chelsea and Westminster NHS Foundation Trust, London, UK (Panagiotis Georgiou, Paris Tekkis)
| | - Niki Karachaliou
- Medical Oncology, Dexeus University Institut, Barcelona, Spain (Niki Carachaliou)
| | - Ourania Katopodi
- Medical Oncology, "Iaso" General Hospital, Athens, Greece (Ourania Katopoidi)
| | - Panteleimon Kountourakis
- Medical Oncology, Oncology Center of Bank of Cyprus, Nicosia, Cyprus (Pandelis Kountourakis, Demetris Papamichael)
| | - Ioannis Kyriazanos
- General Surgery, Athens Naval & Veterans Hospital, Greece (Christos Agalianos, Ioannis Kyriazanos, George Pechlivanides)
| | - Thomas Makatsoris
- Medical Oncology, University Hospital of Patras, Greece (Thomas Makatsoris)
| | - Pavlos Papakostas
- Medical Oncology, "Ippokrateion" Hospital of Athens, Greece (Pavlos Papakostas)
| | - Demetris Papamichael
- Medical Oncology, Oncology Center of Bank of Cyprus, Nicosia, Cyprus (Pandelis Kountourakis, Demetris Papamichael)
| | - George Pechlivanides
- General Surgery, Athens Naval & Veterans Hospital, Greece (Christos Agalianos, Ioannis Kyriazanos, George Pechlivanides)
| | | | - Ioannis Pilpilidis
- Gastroenterology, "Theageneion" Cancer Hospital, Thessaloniki, Greece (Ioannis Pilpilidis)
| | - Joseph Sgouros
- Medical Oncology, "Agioi Anargyroi" Hospital of Athens, Greece (Joseph Sgouros)
| | - Paris Tekkis
- Colorectal Surgery, Chelsea and Westminster NHS Foundation Trust, London, UK (Panagiotis Georgiou, Paris Tekkis)
| | | | - Maria Tzardi
- Pathology, University Hospital of Heraklion, Greece (Maria Tzardi)
| | - Vassilis Vassiliou
- Radiation Oncology, Oncology Center of Bank of Cyprus, Nicosia, Cyprus (Vassilis Vassiliou)
| | - Louiza Vini
- Radiation Oncology, "Iatriko" Center of Athens, Greece (Lousa Vini)
| | - Spyridon Xynogalos
- Medical Oncology, "George Gennimatas" General Hospital, Athens, Greece (Spyridon Xynogalos)
| | - Nikolaos Ziras
- Medical Oncology, "Metaxas" Cancer Hospital, Piraeus, Greece (Nikolaos Ziras)
| | - John Souglakos
- Medical Oncology, University Hospital of Heraklion, Greece (John Souglakos)
| |
Collapse
|
|
21
|
Lin CC, Hung CF, Chen WT, Lin SM. Hepatic Arterial Infusion Chemotherapy for Advanced Hepatocellular Carcinoma with Portal Vein Thrombosis: Impact of Early Response to 4 Weeks of Treatment. Liver Cancer 2015; 4:228-40. [PMID: 26734578 PMCID: PMC4698647 DOI: 10.1159/000367737] [Citation(s) in RCA: 22] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/04/2023] Open
Abstract
AIM The aim of the study was to investigate the impact of early response (ER) to hepatic arterial infusion chemotherapy (HAIC) on outcomes of patients with advanced hepatocellular carcinoma (HCC) complicated with major portal vein tumor thrombosis (PVTT). METHODS Thirty-nine patients receiving HAIC with low-dose cisplatin, 5-fluorouracil (5FU), and leucovorin were enrolled. One course of HAIC consisted of 5 days of treatment and 2 days rest per week for 4 consecutive weeks. ER was categorized as complete response, partial response, or minor response and was determined by World Health Organization criteria with dynamic computed tomography findings performed within 1 week after the first course of HAIC. RESULTS Thirteen (33%) patients achieved an ER. Twelve (92.3%) of these 13 ER patients achieved a higher overall response than all but one (3.8%) of the 26 non-early responders (NERs) (p<0.001). ER was the exclusive independent favorable factor for survival (p=0.003). Downstaging of tumors was noted in 76.9% of ERs, and these patients could proceed to locoregional therapies. ER patients subsequently had a higher 1-year survival (76.9% vs. 3.8%, p<0.001) and 6-month progression-free survival (PFS) (84.6% vs. 15.4%, p<0.001) than those for NERs. Only 8% of patients experienced grade 3 or higher toxicity during the first 4-week course of HAIC. CONCLUSIONS HAIC can yield a satisfactory ER for advanced HCC with PVTT. Moreover, achievement of ER after HAIC in advanced HCC with PVTT is strongly associated with better overall survival and PFS.
Collapse
Affiliation(s)
- Chen-Chun Lin
- Department of Gastroenterology and Hepatology, Chang Gung Memorial Hospital and Chang Gung University, College of Medicine, Taoyuan, Taiwan (ROC)
| | - Chien-Fu Hung
- Division of Diagnostic Radiology and Department of Radiology, Chang Gung Memorial Hospital and Chang Gung University, College of Medicine, Taoyuan, Taiwan (ROC)
| | - Wei-Ting Chen
- Department of Gastroenterology and Hepatology, Chang Gung Memorial Hospital and Chang Gung University, College of Medicine, Taoyuan, Taiwan (ROC)
| | - Shi-Ming Lin
- Department of Gastroenterology and Hepatology, Chang Gung Memorial Hospital and Chang Gung University, College of Medicine, Taoyuan, Taiwan (ROC),*Shi-Ming Lin, MD, Department of Gastroenterology and Hepatology, Chang Gung Memorial, Hospital and Chang Gung University, College of Medicine, 5 Fu-Hsin St., Kwei-Shan, Taoyuan, Taiwan 333 (ROC), Tel. +886 3 328 1200 Ext. 8107, E-mail
| |
Collapse
|
|
22
|
Regional Arterial Infusion Chemotherapy improves the Pathological Response rate for advanced gastric cancer with Short-term Neoadjuvant Chemotherapy. Sci Rep 2015; 5:17516. [PMID: 26620627 PMCID: PMC4664910 DOI: 10.1038/srep17516] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/24/2015] [Accepted: 10/30/2015] [Indexed: 12/29/2022] Open
Abstract
To identify clinicopathologic and treatment variables that could predict pathologic tumor response to short-term neoadjuvant chemotherapy (NAC) for patients with locally advanced gastric cancer. A retrospective analysis was conducted of 178 patients who underwent short-term NAC with EOX regimen followed by surgery from January 2008 to December 2010. Neoadjuvant treatment response was evaluated using tumor regression grade. Relationships between pathologic tumor response and clinicopathological factors were evaluated using logistic regression analysis. The benefits of regional arterial infusion chemotherapy were investigated separately. The postoperative pathological response rate was 46.1% (82/178) and 4 patients (2.2%) had complete pathological remission. Pathological response was significantly associated with tumor differentiation (P = 0.008), abnormal a-fetoprotein levels (P = 0.01) and administration approach to chemotherapy (intravenous versus regional arterial infusion chemotherapy) (P = 0.018). Most bone marrow toxicities, vomiting, nausea, alopecia, and fatigue were acceptable. Grade 3/4 toxicities were not commonly observed. The 3-year overall survival (OS) and recurrence free survival (RFS) were 67.0% and 53.0%, respectively. Regional arterial infusion NAC group had significantly better median RFS (48.0 versus 34.0 months) than the intravenous NAC group (P = 0.049). In conclusion, regional arterial infusion NAC can improve the pathological response rate of advanced gastric cancer treated with EOX regimen.
Collapse
|
|
23
|
Subramanian M, Choti MA, Yopp AC. Hepatic Arterial Infusion Pump Chemotherapy for Colorectal Liver Metastases: Making a Comeback? CURRENT COLORECTAL CANCER REPORTS 2015. [DOI: 10.1007/s11888-015-0277-2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/28/2022]
|
|
24
|
Abstract
Transarterial therapies in the setting of primary and secondary liver malignancies are becoming an essential part of the oncology landscape. Most patients with hepatic malignancies are not candidates for curative surgical intervention, thereby warranting exploration of alternative means of treatment that preserves quality of life while providing clinical benefit. Herein, the data for intra-arterial chemoinfusion, transarterial chemoembolization, drug-eluting beads, and radioembolization are discussed in the setting of malignancies within the liver; outcome data relating to survival, time-to-progression, time-to-recurrence, and adverse events are presented. Further data regarding different treatment paradigms for hepatocellular carcinoma, metastatic colorectal carcinoma, neuroendocrine tumours, and intrahepatic cholangiocarcinoma are also provided. In light of these and forthcoming data, transarterial therapies seem to offer a viable treatment pathway for select populations of patients.
Collapse
|
|
25
|
Phase I trial of hepatic arterial infusion (HAI) of floxuridine with modified oxaliplatin, 5-fluorouracil and leucovorin (m-FOLFOX6) in Chinese patients with unresectable liver metastases from colorectal cancer. Cancer Chemother Pharmacol 2014; 74:1079-87. [PMID: 25217393 DOI: 10.1007/s00280-014-2585-7] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/16/2014] [Accepted: 09/01/2014] [Indexed: 01/26/2023]
Abstract
PURPOSE To determine the maximum tolerated dose (MTD) and preliminary efficacy of concurrent hepatic arterial infusion (HAI) of floxuridine (FUDR) and systemic modified oxaliplatin, 5-fluorouracil and leucovorin (m-FOLFOX6) in Chinese patients with unresectable hepatic metastases from colorectal cancer. PATIENTS AND METHODS Thirty-five patients with unresectable liver metastases with or without extrahepatic disease were treated with concurrent HAI and systemic m-FOLFOX6. HAI FUDR was delivered in a 14-day infusion with escalating dose levels, and each cycle was repeated every 4 weeks. RESULTS The MTD for FUDR was 0.12 mg/kg/day when combined with systemic m-FOLFOX6. The dose-limited toxicities were neutropenia (8.6 %), alanine aminotransferase/aspartate aminotransferase elevation (5.7 %) and diarrhea (11.4 %). The overall response rate was 68.6 % for hepatic metastases and 14.3 % for extrahepatic metastases. The median progression-free survival and overall survival were 8.23 and 25 months, respectively. CONCLUSION The recommended dose of FUDR was 0.12 mg/kg/day when combined with systemic m-FOLFOX6. This combination achieved a high response rate in hepatic disease and a high control rate in extrahepatic disease. Further study is needed to assess the potential additional value of HAI therapy in converting patients with hepatic metastases to candidates for resection.
Collapse
|
|
26
|
Macedo FIB, Makarawo T. Colorectal hepatic metastasis: Evolving therapies. World J Hepatol 2014; 6:453-463. [PMID: 25067997 PMCID: PMC4110537 DOI: 10.4254/wjh.v6.i7.453] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/28/2013] [Revised: 02/23/2014] [Accepted: 06/03/2014] [Indexed: 02/06/2023] Open
Abstract
The approach for colorectal hepatic metastasis has advanced tremendously over the past decade. Multidrug chemotherapy regimens have been successfully introduced with improved outcomes. Concurrently, adjunct multimodal therapies have improved survival rates, and increased the number of patients eligible for curative liver resection. Herein, we described major advancements of surgical and oncologic management of such lesions, thereby discussing modern chemotherapeutic regimens, adjunct therapies and surgical aspects of liver resection.
Collapse
|
|
27
|
Xing M, Kooby DA, El-Rayes BF, Kokabi N, Camacho JC, Kim HS. Locoregional therapies for metastatic colorectal carcinoma to the liver--an evidence-based review. J Surg Oncol 2014; 110:182-96. [PMID: 24760444 DOI: 10.1002/jso.23619] [Citation(s) in RCA: 26] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/31/2013] [Accepted: 03/18/2014] [Indexed: 12/17/2022]
Abstract
The liver is the most common visceral site of colorectal cancer metastasis and recurrence. Given that only 25% of patients with colorectal liver metastases are amenable to curative surgical resection at initial diagnosis, locoregional intra-arterial therapies including hepatic arterial infusion chemotherapy, conventional transarterial chemoembolization, drug-eluting-bead transarterial chemoembolization, and radioembolization have increasingly developed as viable treatment options. The rationale, efficacy, safety, and toxicity of each of these therapies are reviewed and stratified based on current evidence.
Collapse
Affiliation(s)
- Minzhi Xing
- Division of Interventional Radiology, Department of Radiology, University of Pittsburgh Cancer Institute, University of Pittsburgh School of Medicine, Pittsburgh, PA; Interventional Radiology and Image-Guided Medicine, Department of Radiology and Imaging Sciences, Emory University School of Medicine, Atlanta, Georgia
| | | | | | | | | | | |
Collapse
|
|
28
|
Eichler K, Dufas T, Hammerstingl R, Gruber-Rouh T, Vogl T, Zangos S. Hepatic Arterial Infusion with Irinotecan in Patients with Liver Metastases of Colorectal Cancer: Results of an Extended Phase I Study. Chemotherapy 2013; 59:66-73. [DOI: 10.1159/000348579] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/13/2012] [Accepted: 02/03/2013] [Indexed: 01/22/2023]
|
|
29
|
Kemeny NE. The re-birth of hepatic arterial infusion for colorectal liver metastases. J Gastrointest Oncol 2013; 4:118-20. [PMID: 23730505 DOI: 10.3978/j.issn.2078-6891.2013.019] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/13/2023] Open
Affiliation(s)
- Nancy E Kemeny
- Memorial Sloan-Kettering Cancer Center; Weill Medical College at Cornell University, New York, USA
| |
Collapse
|
|
30
|
Abdalla EK, Bauer TW, Chun YS, D'Angelica M, Kooby DA, Jarnagin WR. Locoregional surgical and interventional therapies for advanced colorectal cancer liver metastases: expert consensus statements. HPB (Oxford) 2013; 15:119-30. [PMID: 23297723 PMCID: PMC3719918 DOI: 10.1111/j.1477-2574.2012.00597.x] [Citation(s) in RCA: 70] [Impact Index Per Article: 5.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/16/2012] [Accepted: 08/20/2012] [Indexed: 12/12/2022]
Abstract
Selection of the optimal surgical and interventional therapies for advanced colorectal cancer liver metastases (CRLM) requires multidisciplinary discussion of treatment strategies early in the trajectory of the individual patient's care. This paper reports on expert consensus on locoregional and interventional therapies for the treatment of advanced CRLM. Resection remains the reference treatment for patients with bilateral CRLM and synchronous presentation of primary and metastatic cancer. Patients with oligonodular bilateral CRLM may be candidates for one-stage multiple segmentectomies; two-stage resection with or without portal vein embolization may allow complete resection in patients with more advanced disease. After downsizing with preoperative systemic and/or regional therapy, curative-intent hepatectomy requires resection of all initial and currently known sites of disease; debulking procedures are not recommended. Many patients with synchronous primary disease and CRLM can safely undergo simultaneous resection of all disease. Staged resections should be considered for patients in whom the volume of the future liver remnant is anticipated to be marginal or inadequate, who have significant medical comorbid condition(s), or in whom extensive resections are required for the primary cancer and/or CRLM. Priority for liver-first or primary-first resection should depend on primary tumour-related symptoms or concern for the progression of marginally resectable CRLM during treatment of the primary disease. Chemotherapy delivered by hepatic arterial infusion represents a valid option in patients with liver-only disease, although it is best delivered in experienced centres. Ablation strategies are not recommended as first-line treatments for resectable CRLM alone or in combination with resection because of high local failure rates and limitations related to tumour size, multiplicity and intrahepatic location.
Collapse
Affiliation(s)
- Eddie K Abdalla
- Department of Surgery, Lebanese American UniversityBeirut, Lebanon
| | - Todd W Bauer
- Department of Surgery, University of Virginia Health SystemCharlottesville, VA, USA
| | - Yun S Chun
- Department of Surgical Oncology, Fox Chase Cancer CenterPhiladelphia, PA, USA
| | - Michael D'Angelica
- Department of Surgery, Memorial Sloan–Kettering Cancer CenterNew York, NY, USA
| | - David A Kooby
- Department of Surgery, Emory University School of MedicineAtlanta, GA, USA
| | - William R Jarnagin
- Department of Surgery, Memorial Sloan–Kettering Cancer CenterNew York, NY, USA
| |
Collapse
|
|
31
|
Wanebo HJ, LeGolvan M, Paty PB, Saha S, Zuber M, D’Angelica MI, Kemeny NE. Meeting the biologic challenge of colorectal metastases. Clin Exp Metastasis 2012; 29:821-39. [DOI: 10.1007/s10585-012-9517-x] [Citation(s) in RCA: 37] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/09/2012] [Accepted: 07/09/2012] [Indexed: 12/20/2022]
|
|
32
|
Lewandowski RJ, Geschwind JF, Liapi E, Salem R. Transcatheter intraarterial therapies: rationale and overview. Radiology 2011; 259:641-57. [PMID: 21602502 PMCID: PMC3400295 DOI: 10.1148/radiol.11081489] [Citation(s) in RCA: 177] [Impact Index Per Article: 12.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
Transcatheter intraarterial therapies have proved valuable in the battle against primary and secondary hepatic malignancies. The unique aspects of all such therapies are their reduced toxicity profiles and highly effective tumor responses. These unique characteristics coupled with their minimally invasive nature provide an attractive therapeutic option in patients who may have previously had few alternatives. The concept of all catheter-based intraarterial therapies is to selectively deliver anticancer treatment to tumor(s). These therapies, which include transarterial embolization, intraarterial chemoinfusion, transarterial chemoembolization with or without drug-eluting beads, and radioembolization with use of yttrium 90, inflict lethal insult to tumors while preserving normal hepatic parenchyma. This is possible because hepatic neoplasms preferentially derive their blood supply from an arterial source while the majority of noncancerous liver is supplied by the portal vein. As part of the interventional oncology review series, in this article we describe the rationale behind each of these transcatheter therapies and provide a review of the existing medical literature.
Collapse
Affiliation(s)
- Robert J Lewandowski
- Department of Radiology, Section of Interventional Radiology, Northwestern University Feinberg School of Medicine, Northwestern Memorial Hospital, Robert H. Lurie Comprehensive Cancer Center, 676 N St Clair St, Suite 800, Chicago, IL 60611, USA.
| | | | | | | |
Collapse
|
|
33
|
Abstract
INTRODUCTION Primary and secondary liver tumors resemble some of the most common causes of cancer and represent a major clinical problem owing to the poor prognosis. First-line therapeutic concepts are mainly based on surgical resection and/or systemic chemotherapy (SCT). However, many patients are not suitable for surgery or have failed SCT, although the total tumor load is still limited, which makes a regional therapy approach appealing. AREAS COVERED This review focuses on different types of transarterial instillation of chemotherapy, which encompasses conventional and drug-eluting transarterial chemoembolization (TACE), hepatic arterial infusion (HAI) chemotherapy and isolated hepatic perfusion (ILP). EXPERT OPINION TACE can be regarded as the treatment of choice in patients with multinodular hepatocellular carcinoma, but it should still be performed as a lipiodol-based regimen, while the value of doxorubicin-eluting beads needs to be exploited in further randomized controlled trials (RCTs). For patients with colorectal liver metastases, HAI chemotherapy has been challenged by the advent of more effective SCT, but encouraging results have been observed for the combination of the most recent, active drugs given by means of HAI with SCT. Nevertheless, data from RCTs comparing SCT with this transarterial regional therapy approach, as well as with TACE and ILP, are urgently needed.
Collapse
Affiliation(s)
- Oliver Dudeck
- Department of Radiology and Nuclear Medicine, University of Magdeburg, Magdeburg, Germany.
| | | |
Collapse
|
|
34
|
Lee HJ, Lee YS, Lee KW, Kim SY, Yoon CJ, Shin DY, Lee YG, Choi SY, Kang SG, Kang SB, Kim JH. Efficacy and safety of hepatic arterial infusion of fluorouracil with leucovorin as salvage treatment for refractory liver metastases from colorectal cancer. Korean J Intern Med 2011; 26:82-8. [PMID: 21437167 PMCID: PMC3056261 DOI: 10.3904/kjim.2011.26.1.82] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/30/2010] [Revised: 10/06/2010] [Accepted: 10/26/2010] [Indexed: 01/18/2023] Open
Abstract
BACKGROUND/AIMS Limited options remain for patients with metastatic colorectal cancer (CRC) after failure of standard systemic chemotherapy. Readministration of chemotherapeutic agents by hepatic arterial infusion (HAI) has the rationale of providing higher concentrations of chemotherapeutic agents to hepatic metastases. The present study was conducted to evaluate the efficacy and safety of HAI of fluorouracil with leucovorin (HAI 5-FU/LV) for patients with liver metastases from CRC. METHODS Fourteen patients with liver metastases from CRC who received HAI 5-FU/LV after failure of systemic chemotherapy containing fluorouracil and leucovorin were identified and their medical records were reviewed. RESULTS Of 10 patients evaluable for response, one partial response, six stable disease, and three progressive disease were reported. Additionally, the overall response and disease control rates were 7% and 50%, respectively. The median time to progression was 4.3 months (range, 2.9 to 5.6), to hepatic progression was 5.8 months (range, 4.7 to 6.9), and to extrahepatic progression was 5.8 months (range, 2.3 to 9.2). No grade 3/4 hematologic toxicities occurred and one case of abdominal pain and two cases of oral mucositis were the only grade 3 nonhematologic toxicities. Catheter-related complications occurred in three patients: one thrombosis, one infection, and one displacement. CONCLUSIONS HAI 5-FU/LV was well tolerated and showed modest efficacy for patients with liver metastases from refractory CRC. Readministration of previously used chemotherapeutic agents via the hepatic artery could be an effective salvage option and warrants further investigation in a prospective trial.
Collapse
Affiliation(s)
- Hyun Jung Lee
- Department of Internal Medicine, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seongnam, Korea
| | - Yoon Soo Lee
- Department of Internal Medicine, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seongnam, Korea
| | - Keun-Wook Lee
- Department of Internal Medicine, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seongnam, Korea
| | - So Yeon Kim
- Department of Radiology, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seongnam, Korea
| | - Chang Jin Yoon
- Department of Radiology, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seongnam, Korea
| | - Dong-Yeop Shin
- Department of Internal Medicine, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seongnam, Korea
| | - Yun Gyoo Lee
- Department of Internal Medicine, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seongnam, Korea
| | - Se Yeon Choi
- Department of Internal Medicine, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seongnam, Korea
| | - Sung-Gwon Kang
- Department of Radiology, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seongnam, Korea
| | - Sung-Bum Kang
- Department of Surgery, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seongnam, Korea
| | - Jee Hyun Kim
- Department of Internal Medicine, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seongnam, Korea
| |
Collapse
|
|
35
|
Samaras P, Breitenstein S, Haile SR, Stenner-Liewen F, Heinrich S, Feilchenfeldt J, Renner C, Knuth A, Pestalozzi BC, Clavien PA. Selective intra-arterial chemotherapy with floxuridine as second- or third-line approach in patients with unresectable colorectal liver metastases. Ann Surg Oncol 2011; 18:1924-31. [PMID: 21207165 DOI: 10.1245/s10434-010-1505-2] [Citation(s) in RCA: 13] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/02/2010] [Indexed: 01/01/2023]
Abstract
BACKGROUND An outcome assessment was performed of patients with unresectable colorectal liver metastases (CRLM) treated in second or third line with floxuridine (FUDR)-based hepatic artery infusion (HAI). METHODS Twenty-three patients who were pretreated with systemic (immuno)chemotherapy received FUDR-HAI alone or combined with systemic chemotherapy. We reviewed patient charts and our prospective patient database for survival and associated risk factors. RESULTS Patients received FUDR-HAI for unresectable CRLM from January 2000 to September 2010. Twelve patients (52%) received concurrent systemic chemotherapy. Median overall survival (OS), progression-free survival (PFS), and hepatic PFS were 15.6 months (range, 2.5-55.7 months), 3.9 months (range, 0.7-55.7 months), and 5.5 months (range, 1.6-55.7 months), respectively. The liver resection rate after HAI was 35%. PFS was better in patients undergoing secondary resection than in patients without resection (hazard ratio [HR] 0.21; 95% confidence interval [95% CI] 0.07-0.66; P = 0.0034), while OS showed a trend toward improvement (HR 0.4; 95% CI 0.13-1.2; P = 0.09). No differences were observed in OS (P = 0.69) or PFS (P = 0.086) in patients who received FUDR-HAI alone compared with patients treated with combined regional and systemic chemotherapy. No statistically significant differences were seen in patients previously treated with one chemotherapy line compared with patients treated with two lines. Presence of extrahepatic disease was a negative risk factor for PFS (liver-only disease: HR 0.03; 95% CI 0.0032-0.28; P < 0.0001). Toxicities were manageable with dose modifications and supportive measures. CONCLUSIONS FUDR-HAI improves PFS and results in a trend toward improved OS in selected patients able to undergo liver resection after tumor is downsized.
Collapse
Affiliation(s)
- Panagiotis Samaras
- Department of Oncology and Surgery, University Hospital Zurich, Zurich, Switzerland
| | | | | | | | | | | | | | | | | | | |
Collapse
|
|
36
|
Kulaylat MN, Gibbs JF. Regional treatment of colorectal liver metastasis. J Surg Oncol 2010; 101:693-8. [DOI: 10.1002/jso.21503] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/07/2022]
|
|
37
|
Abstract
Neuroendocrine tumors (NETs) comprise a diverse group of slowly growing tumors with an indolent course, characterized by the capacity to synthesize and secrete polypeptide products that are hormonally active. Presence of liver metastases results in significant debilitating hormonal symptoms, and is associated with poor prognosis. Systemic chemotherapy has limited success in the management of patients with NET hepatic metastases. Although somatostatin analogs are effective in controlling symptoms in many of these patients, the disease can become refractory to treatment. For these reasons, interventional radiologic techniques for liver-directed therapy have become an important treatment option in patients with metastatic NETs. Transcatheter arterial procedures such as transarterial embolization (TAE), transarterial chemoembolization (TACE), and selective internal radiation therapy (SIRT) have been shown to reduce hormone levels, palliate symptoms, and reduce the tumor burden in many patients with unresectable and symptomatic NET hepatic metastases. This article summarizes the most recent information on arterial-based liver-directed therapies in the treatment of metastatic NETs.
Collapse
Affiliation(s)
- Javier Nazario
- Department of Diagnostic Radiology, The University of Texas M.D. Anderson Cancer Center, Houston, TX 77030, USA
| | | |
Collapse
|
|
38
|
|
|
39
|
Abstract
Surgical resection is the most effective treatment modality for liver metastases from colorectal cancer. However, most patients with liver metastases are not candidates for resection due to extensive intrahepatic disease. Approximately one-half of the patients who are able to undergo resection will eventually recur within the remnant liver. Hepatic arterial infusion (HAI) chemotherapy takes advantage of the arterial blood supply of colorectal liver metastases to increase tumor exposure to chemotherapy while minimizing systemic toxicity. HAI chemotherapy has been utilized in patients with unresectable disease in the neoadjuvant setting in an effort to convert them to resectability as well as in patients with resectable disease in the adjuvant setting in an effort to prevent recurrence. This article reviews the roles of HAI chemotherapy in an aggressive approach toward colorectal liver metastases.
Collapse
Affiliation(s)
- Rebekah R White
- Surgical Oncology Fellow, Memorial Sloan-Kettering Cancer Center, New York, New York 10021, USA
| | | |
Collapse
|
|
40
|
Christante D, Pommier S, Givi B, Pommier R. Hepatic artery chemoinfusion with chemoembolization for neuroendocrine cancer with progressive hepatic metastases despite octreotide therapy. Surgery 2008; 144:885-93; discussion 893-4. [PMID: 19040993 DOI: 10.1016/j.surg.2008.08.037] [Citation(s) in RCA: 35] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/11/2008] [Accepted: 08/27/2008] [Indexed: 11/26/2022]
Abstract
BACKGROUND Hepatic metastases from neuroendocrine cancer dramatically reduce survival, introducing an important opportunity for intervention. Several treatment modalities have been examined, but an optimal treatment approach has been difficult to define. We evaluated a regimen combining hepatic artery chemoinfusion with chemoembolization. METHODS Patients with neuroendocrine cancer and diffuse hepatic metastases were treated with hepatic artery chemoinfusion and chemoembolization when they demonstrated disease progression despite octreotide therapy. Four monthly cycles of 5-fluorouracil were administered via hepatic artery infusion with chemoembolization after the final 2 cycles. Response was defined by radiologic response or symptomatic improvement. RESULTS Seventy-seven patients were treated; 18 received chemoinfusion only. The treatment-related mortality rate was 7%. The overall response rate was 80% for patients with carcinoid or islet cell neoplasms. Median progression-free survival was 19 months. Median disease-specific survival was 39 months from the first treatment; 1- and 5-year survival rates were 78% and 27%, respectively. CONCLUSION Survival after initiating this regimen was over 3 years for the majority of patients exhibiting progression of extensive, unresectable hepatic disease despite octreotide therapy. The addition of hepatic artery chemoinfusion to chemoembolization offers a high probability of clinical benefit to patients who, otherwise, have severely limited therapeutic options and a dismal survival.
Collapse
Affiliation(s)
- Dara Christante
- Department of Surgery, Division of Surgical Oncology, Oregon Health & Science University, Portland, Ore, USA
| | | | | | | |
Collapse
|
|
41
|
Dizon DS, Schwartz J, Kemeny N. Regional chemotherapy: a focus on hepatic artery infusion for colorectal cancer liver metastases. Surg Oncol Clin N Am 2008; 17:759-71, viii. [PMID: 18722916 DOI: 10.1016/j.soc.2008.04.009] [Citation(s) in RCA: 26] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/15/2023]
Abstract
Regional infusion strategies have been used as a treatment modality in multiple cancers, including ovarian, appendiceal, and colorectal cancers. Perhaps the most illustrative use of regional therapy is that of hepatic arterial infusion (HAI) for liver metastases from colorectal cancer. The administration of chemotherapy by HAI is logical and has theoretic advantages over systemic chemotherapy for the treatment of hepatic metastases from colorectal cancer. With the use of an appropriately chosen chemotherapy agent, HAI can generate an increase in hepatic tumor drug exposure as compared with intravenous delivery of the same agent. This article reviews the pharmacologic benefits of HAI therapy and the contemporary trials performed and underway.
Collapse
Affiliation(s)
- Don S Dizon
- Program in Women's Oncology, Department of Obstetrics and Gynecology, Women & Infants' Hospital, Warren Alpert Medical School of Brown University, 101 Dudley Street, Providence, RI 02905, USA.
| | | | | |
Collapse
|
|
42
|
Abstract
Regional chemotherapy was developed in the 1950s and continues to play an integral part in the development of newer therapies for advanced solid malignancies. Regional therapies have evolved in complexity but are still based on the pharmacokinetics of drug delivery to solid malignancies. Newer techniques demonstrate that the combination of regional therapies, hyperthermia, and surgery is essential in promoting improved patient outcomes.
Collapse
|
|
43
|
Power DG, Healey-Bird BR, Kemeny NE. Regional Chemotherapy for Liver-Limited Metastatic Colorectal Cancer. Clin Colorectal Cancer 2008; 7:247-59. [DOI: 10.3816/ccc.2008.n.032] [Citation(s) in RCA: 23] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/18/2023]
|
|
44
|
Carnaghi C, Santoro A, Rimassa L, Doci R, Rosati R, Pedicini V, Gullo G, Zuradelli M, Abbadessa G, Morenghi E, Marcon I, Garassino I. The efficacy of hybrid chemotherapy with intravenous oxaliplatin and folinic acid and intra-hepatic infusion of 5-fluorouracil in patients with colorectal liver metastases: a phase II study. Invest New Drugs 2007; 25:479-85. [PMID: 17492399 DOI: 10.1007/s10637-007-9048-5] [Citation(s) in RCA: 11] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/07/2007] [Accepted: 03/20/2007] [Indexed: 12/27/2022]
Abstract
Intra-arterial chemotherapy in patients with liver metastases from colorectal cancer has some limitations such as hepatic toxicity and extra-hepatic progression. With the aim of overcoming these limitations, a phase II trial was designed to assess the efficacy and tolerability of a hybrid chemotherapy regimen with systemic infusion of oxaliplatin and folinic acid associated with intra-arterial 5-fluorouracil. Thirty-nine patients with colorectal liver metastases were recruited. The median age was 59 years, 30 patients (77%) had synchronous metastases, and half of the patients were chemo-naive. A total of 313 chemotherapy cycles were administered (median number 8). Treatment was well tolerated and hepatic toxicity negligible. Out of 34 evaluable patients an ORR of 41%. was observed. Eight patients (21%) underwent radical liver surgery. The median time to progression (TTP) was 10 months (range 2-63) and the median overall survival (OS) 21 months (range 6-63). Extra-hepatic progression was observed in six patients. Our results suggest that this regimen is active even if technical complications are frequent. Our aim to reduce hepatic toxicity and extra-hepatic progression was reached.
Collapse
Affiliation(s)
- Carlo Carnaghi
- Department of Medical Oncology and Hematology, Istituto Clinico Humanitas, Via Manzoni 56, 20089 Rozzano (Milano), Italy.
| | | | | | | | | | | | | | | | | | | | | | | |
Collapse
|
|
45
|
Yoshikawa T, Uchida K, Ohno Y, Hirota S, Nakamura T, Yoshizako T, Ishida J, Kitagaki H. A simple catheter-vessel model for MR assessment of drug distribution in arteries and optimization of catheter design for intraarterial infusion therapy. J Magn Reson Imaging 2007; 25:1044-50. [PMID: 17457800 DOI: 10.1002/jmri.20912] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/10/2022] Open
Abstract
PURPOSE To investigate the efficacy of a new catheter-vessel model for MRI to evaluate drug distribution and to optimize catheter design for intraarterial infusion therapy MATERIALS AND METHODS The model consisted of a hepatic artery simulant tube through which blood simulant water flowed continuously and a water cistern. Catheters were inserted into the tube and a gadolinium contrast medium was injected at rates suitable for angiographic or computed tomographic evaluation and commensurate with the clinical drug infusion rate. Axial images of the tube were obtained with a 0.2-T scanner and gradient echo technique. Preliminary studies and catheter tests were conducted. The points at which drug and water were completely mixed were defined as the site with uniform enhancement nearest the catheter tip. RESULTS Flip angle and gadolinium concentrations were optimized at 90 degrees, and at 62.5 and 500 mM for the high and low infusion rates, respectively. Drug distribution near the catheter tips was clearly visualized. The drug was mixed in shorter distances via the slit side-hole than the end- or side-hole catheters, and the smaller diametrical than the larger at either rate. CONCLUSION This model appeared to be effective for evaluation of drug distribution and optimization of catheter design.
Collapse
Affiliation(s)
- Takeshi Yoshikawa
- Department of Radiology, Kobe University Graduate School of Medicine, 7-5-2 Kusunokicho, Chuoku, Kobe 650-0017, Japan. yoshikawa@
| | | | | | | | | | | | | | | |
Collapse
|
|
46
|
Abstract
For the past several decades, the therapy for metastatic colorectal cancer had modest benefits because of the limited therapeutic options. Bolus 5-fluorouracil (5FU) and leucovorin (LV) were the standard of care in the United States until 2002, with a response rate of 25% and a median survival of 10 to 12 months. However, with the advent of new agents, namely oxaliplatin and irinotecan, there has been a dramatic change in the way we treat metastatic colorectal cancer. Based on many well-conducted large randomized trials, we have evidence that combination chemotherapy incorporating oxaliplatin or irinotecan with infusional 5FU/LV is superior to 5FU/LV, with doubling of overall survival (OS) to approximately 20 months. There remains some uncertainty as to the best first-line regimen. This might be irrelevant because studies have shown that OS is dependent on exposure to all the active agents, regardless of the time period of exposure. Bevacizumab, which uses anti-angiogenic strategies, has improved disease-free survival (DFS) and OS when combined with standard chemotherapy and is a vital component of metastatic colorectal cancer therapy. However, there are no data supporting its use past progression. Cetuximab, an epithelial growth factor receptor inhibitor, is mainly used in irinotecan-refractory patients. In spite of all these advances, 5-year OS rates continue to be limited. Patients with curative resection of metastatic disease seem to have longer DFS and better 5-year OS rates. This should be a potential goal for responding patients with upfront unresectable, organ-limited disease.
Collapse
Affiliation(s)
- Smitha Patiyil
- Division of Medical Oncology, Mayo Clinic, Rochester, MN 55905, USA
| | | |
Collapse
|
|
47
|
Nakchbandi W, Müller H, Singer MV, Löhr M, Nakchbandi IA. Effects of low-dose warfarin and regional chemotherapy on survival in patients with pancreatic carcinoma. Scand J Gastroenterol 2006; 41:1095-104. [PMID: 16938724 DOI: 10.1080/00365520600575720] [Citation(s) in RCA: 19] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/04/2023]
Abstract
OBJECTIVE To report the effect of regional combination chemotherapy in a cohort of patients with inoperable pancreatic carcinoma treated with or without low-dose warfarin. MATERIAL AND METHODS A retrospective analysis was performed on 180 patients with pancreatic carcinoma. Patients received one of seven regimens of chemotherapy. Unrelated to the type of chemotherapy, some patients received 1.25 mg warfarin daily. The primary end-point was median survival. RESULTS Treatment with warfarin resulted in improved median survival from the start of regional therapy (warfarin versus no warfarin: 5.0 versus 2.3 months, n = 111 versus 69; p < 0.0001). This effect was not dependent on the type of chemotherapy used. Among the seven regimens examined, the one consisting of regional gemcitabine and mitomycin-C with systemic gemcitabine was associated with the longest median survival of 5.1 months from the start of regional therapy (p = 0.006) and 12.7 months from diagnosis. This regimen combined with warfarin was associated with improved median survival (7.1 months, n = 32). CONCLUSIONS Treatment with low-dose warfarin improved survival irrespective of the chemotherapy received. Of the regimens examined, the combination of regional gemcitabine and mitomycin-C with systemic gemcitabine was associated with the longest survival time. Survival was increased further by the addition of warfarin. These data provide a rationale, based on safety and efficacy, for a definitive study on the use of warfarin and combined regional and systemic chemotherapy in patients with pancreatic carcinoma.
Collapse
Affiliation(s)
- Wes Nakchbandi
- Department of Oncologic Surgery, Carl von Hess Hospital, Hammelburg, Germany
| | | | | | | | | |
Collapse
|
|
48
|
Tentes AAK, Markakidis SK, Karanikiotis C, Fiska A, Tentes IK, Manolopoulos VG, Dimitriou T. Intraarterial chemotherapy as an adjuvant treatment in locally advanced gastric cancer. Langenbecks Arch Surg 2006; 391:124-9. [PMID: 16534653 DOI: 10.1007/s00423-006-0022-z] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/24/2005] [Accepted: 12/21/2005] [Indexed: 10/24/2022]
Abstract
BACKGROUND AND AIMS D2 gastrectomy has improved survival in gastric cancer. Adjuvant intravenous chemotherapy, radiotherapy, or multimodal therapy has failed to demonstrate improved survival. The results of intraarterial chemotherapy (IARC) as an adjuvant have been encouraging in a few studies. A prospective randomized trial was designed to evaluate the toxicity and survival in locally advanced gastric cancer using IARC as an adjuvant after potentially curative gastrectomy. PATIENTS AND METHODS Forty patients with locally advanced gastric cancer were randomly selected to undergo either potentially curative gastrectomy and receive IARC (study group) or gastrectomy only (control group). Clinical and histopathologic data were analyzed and the toxicity related to IARC was recorded. RESULTS The groups were comparable (p>0.05). Three patients in the study group had minor toxicity. Five-year survival rate for the study and the control group was 52 and 54%, respectively (p>0.05). Mean survival for the study and the control group was 50+/-8 and 62+/-10 months, respectively (p>0.05). The number of recurrences and the failure sites were comparable (p>0.05). CONCLUSION Intraarterial chemotherapy can be safely applied to gastric cancer patients. As proposed by the protocol, the method cannot be recommended as an adjuvant treatment for locally advanced tumors because it appears that there is no survival benefit compared to potentially curative gastrectomy alone.
Collapse
|
|
49
|
Neoadjuvant and adjuvant therapy combined with resection of hepatic colorectal cancer metastases. CURRENT COLORECTAL CANCER REPORTS 2006. [DOI: 10.1007/s11888-006-0006-y] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/23/2022]
|
|
50
|
Cosín O, Garrido F, Gil R, Domínguez P, de la Cuesta AM, Ignacio Bilbao J. Reservorio intraarterial hepático para quimioterapia. Colocación percutánea en la arteria subclavia izquierda. RADIOLOGIA 2005. [DOI: 10.1016/s0033-8338(05)72858-7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/16/2022]
|