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Sequential compared to combination chemotherapy with capecitabine, irinotecan, and oxaliplatin in advanced colorectal cancer (ACC): A Dutch Colorectal Cancer group (DCCG) phase III study Authors: Punt et al. Reviewer: Dr Phil Bedard Date posted: June 21, 2007. Background.
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Sequential compared to combination chemotherapy with capecitabine, irinotecan, and oxaliplatin in advanced colorectal cancer (ACC): A Dutch Colorectal Cancer group (DCCG) phase III study Authors: Punt et al. Reviewer: Dr Phil Bedard Date posted: June 21, 2007
Background • FOCUS study (Maughan, ASCO GI 2005) evaluated sequential versus combined use of irinotecan OR oxaliplatin with 5FU • no difference between sequential or combined use but • access to all 3 active chemo drugs restricted in this trial • Exposure to three active cytotoxic drugs prolongs survival in metastatic colorectal cancer (Grothey, JCO 2004) • ? FOCUS outcome altered by restriction of access to all active cytotoxics
Study Question • Is sequential “doublet” combination chemotherapy superior to sequential monotherapy in metastatic colorectal cancer when there is access to all active chemo agents?
Study Design 3rd line 1st line 2nd line Sequential Monotherapy Capecitabine N=397 Irinotecan N=251 Oxaliplatin N=143 Patients with metastatic colorectal cancer and no prior treatment N=795 Capecitabine + Irinotecan N=398 Capecitabine + Oxaliplatin N=213 Sequential Doublets
Results • Quality-of-life scores similar between arms • Toxicity profile different for sequential versus combination in 1st line setting • More hand-foot syndrome in sequential arm • More diarrhea, nausea, vomiting, and febrile neutropenia in combination arm
Study Commentary • Did choice of irinotecan combination reduce efficacy of sequential doublet arm? • BICC-C at ASCO 2007 and EORTC 40015 at ASCO 2006 used same CapeIri regimen as Dutch study with increased toxicity and overall survival detriment (4-5 mos) • Would sequential doublet arm been superior to sequential monotherapy if FOLFIRI used? • Impossible to tell but caution warranted in interpreting results • The role of biologic therapy (ie. VEGF or EGFR targeted therapy) in the schema of treatment will need to be addressed in future studies
Bottom Line for Canadian Medical Oncologists • This study does not definitively answer whether sequential monotherapy can replace sequential doublets