Bevacizumab Increases Efficacy of Oxaliplatin- Based Chemotherapy for Metastatic CRC

NEW YORK-Adding bevacizumab(Drug information on bevacizumab) (Avastin) to oxaliplatin [Eloxatin]/ fluorouracil(Drug information on fluorouracil) or to oxaliplatin(Drug information on oxaliplatin)/ capecitabine(Drug information on capecitabine) (Xeloda) improves response rates and is tolerable as firstline treatment of patients with metastatic colorectal cancer (CRC), Howard S. Hochster, MD, of New York University School of Medicine reported (abstract 3515). TREE-1 and TREE-2 Studies The TREE-1 study (n = 147) examined responses to first-line FOLFOX6 (oxaliplatin, leucovorin, and bolus 5-FU followed by 5-FU infusion); bFOL (oxaliplatin, leucovorin, bolus 5-FU); and CapeOx (capecitabine, oxaliplatin). The TREE-2 study (n = 213) examined the effect of adding bevacizumab to each of these three regimens. The primary study endpoints were overall incidence of grade 3/4 toxici- ties during the first 12 weeks of study therapy. Secondary endpoints were efficacy (overall response rate), time to tumor progression, overall survival, and time to treatment failure. Eligible patients had measurable, untreated metastatic CRC and a performance status of 0 or 1. "The addition of bevacizumab in TREE-2 caused increased grade 3/4 hypertension, impaired wound healing (5%), and bowel perforation (3%) in each arm," Dr. Hochster said. "However, grade 3/4 toxicity with firstline bevacizumab plus oxaliplatinbased chemotherapy is acceptable and is less than reported for IFL (irinotecan [Camptosar], 5-FU, leucovorin)." Treatment-related toxicities are shown in Table 1. Regimens Active All the fluoropyrimidine regimens were active, but Dr. Hochster said that FOLFOX had the best balance of response and toxicity. "Bevacizumab sig- nificantly improved response rates (P = .011) when added to oxaliplatin/ fluoropyrimidine chemotherapy," he said. Confirmed overall response rates were 63.4% with FOLFOX-B, 34.3% with bFOL-B, and 45.8% with CapeOx- B (Table 2). During an oral discussion, Charles Blanke, MD, of Oregon Cancer Institute, Portland, said, "The addition of bevacizumab always increased response, although the confidence intervals overlapped. Bolus 5-FU appeared to be inferior to FOLFOX and probably to capecitabine-oxaliplatin in regard to time to treatment failure."