PURPOSE: This phase III study compared the safety and efficacy of the following three different irinotecan-containing regimens in the first-line treatment of metastatic colorectal cancer: irinotecan plus infusional fluorouracil (FU)/leucovorin (LV) (FOLFIRI), irinotecan plus bolus FU/LV (mIFL), and irinotecan plus oral capecitabine (CapeIRI). PATIENTS AND METHODS: A total of 430 previously untreated metastatic colorectal cancer patients were randomly assigned to receive FOLFIRI (n = 144), mIFL (n = 141), or CapeIRI (n = 145). Patients were concurrently randomly assigned to a double-blind treatment with celecoxib or placebo. After a protocol amendment, an additional 117 patients were randomly assigned to either FOLFIRI plus bevacizumab (FOLFIRI+Bev; n = 57) or mILF plus bevacizumab (mIFL+Bev; n = 60), whereas the CapeIRI arm was discontinued. The primary study end point was progression-free survival (PFS), with secondary end points of overall survival (OS), response rate, and toxicity. RESULTS:Median PFS was 7.6 months for FOLFIRI, 5.9 months for mIFL (P = .004 for the comparison with FOLFIRI), and 5.8 months for CapeIRI (P = .015). Median OS was 23.1 months for FOLFIRI, 17.6 months for mIFL (P = .09), and 18.9 months for CapeIRI (P = .27). CapeIRI was associated with higher rates of severe vomiting, diarrhea, and dehydration. After the amendment to add bevacizumab, the median survival time has not yet been reached for FOLFIRI+Bev and was 19.2 months for mIFL+Bev (P = .007). FOLFIRI+Bev was associated with a higher rate of > or = grade 3 hypertension than mIFL+Bev. CONCLUSION:FOLFIRI and FOLFIRI+Bev offered superior activity to their comparators and were comparably safe. An infusional schedule of FU should be the preferred irinotecan-based regimen in first-line metastatic colorectal cancer.
RCT Entities:
PURPOSE: This phase III study compared the safety and efficacy of the following three different irinotecan-containing regimens in the first-line treatment of metastatic colorectal cancer: irinotecan plus infusional fluorouracil (FU)/leucovorin (LV) (FOLFIRI), irinotecan plus bolus FU/LV (mIFL), and irinotecan plus oral capecitabine (CapeIRI). PATIENTS AND METHODS: A total of 430 previously untreated metastatic colorectal cancerpatients were randomly assigned to receive FOLFIRI (n = 144), mIFL (n = 141), or CapeIRI (n = 145). Patients were concurrently randomly assigned to a double-blind treatment with celecoxib or placebo. After a protocol amendment, an additional 117 patients were randomly assigned to either FOLFIRI plus bevacizumab (FOLFIRI+Bev; n = 57) or mILF plus bevacizumab (mIFL+Bev; n = 60), whereas the CapeIRI arm was discontinued. The primary study end point was progression-free survival (PFS), with secondary end points of overall survival (OS), response rate, and toxicity. RESULTS: Median PFS was 7.6 months for FOLFIRI, 5.9 months for mIFL (P = .004 for the comparison with FOLFIRI), and 5.8 months for CapeIRI (P = .015). Median OS was 23.1 months for FOLFIRI, 17.6 months for mIFL (P = .09), and 18.9 months for CapeIRI (P = .27). CapeIRI was associated with higher rates of severe vomiting, diarrhea, and dehydration. After the amendment to add bevacizumab, the median survival time has not yet been reached for FOLFIRI+Bev and was 19.2 months for mIFL+Bev (P = .007). FOLFIRI+Bev was associated with a higher rate of > or = grade 3 hypertension than mIFL+Bev. CONCLUSION:FOLFIRI and FOLFIRI+Bev offered superior activity to their comparators and were comparably safe. An infusional schedule of FU should be the preferred irinotecan-based regimen in first-line metastatic colorectal cancer.
Authors: Costel Chirila; Dawn Odom; Giovanna Devercelli; Shahnaz Khan; Bintu N Sherif; James A Kaye; István Molnár; Beth Sherrill Journal: Int J Colorectal Dis Date: 2011-11-12 Impact factor: 2.571
Authors: S Yousuf Zafar; Jennifer E Marcello; Jane L Wheeler; Krista L Rowe; Michael A Morse; James E Herndon; Amy P Abernethy Journal: J Oncol Pract Date: 2009-09 Impact factor: 3.840
Authors: Ferenc G Rick; Stephan Seitz; Andrew V Schally; Luca Szalontay; Awtar Krishan; Christian Datz; Andreas Stadlmayr; Stefan Buchholz; Norman L Block; Florian Hohla Journal: Cell Cycle Date: 2012-10-24 Impact factor: 4.534
Authors: Scott Kopetz; Paulo M Hoff; Jeffrey S Morris; Robert A Wolff; Cathy Eng; Katrina Y Glover; Rosie Adinin; Michael J Overman; Vincete Valero; Sijin Wen; Christopher Lieu; Shaoyu Yan; Hai T Tran; Lee M Ellis; James L Abbruzzese; John V Heymach Journal: J Clin Oncol Date: 2009-12-14 Impact factor: 44.544
Authors: Aimery de Gramont; Joleen Hubbard; Qian Shi; Michael J O'Connell; Marc Buyse; Jacqueline Benedetti; Brian Bot; Chris O'Callaghan; Greg Yothers; Richard M Goldberg; Charles D Blanke; Al Benson; Qiqi Deng; Steven R Alberts; Thierry Andre; Norman Wolmark; Axel Grothey; Daniel Sargent Journal: J Clin Oncol Date: 2009-12-14 Impact factor: 44.544