Adding Bevacizumab Improves Response to Oxaliplatin Regimens

HOLLYWOOD, Florida-Preliminary data from the TREE-2 randomized study of first-line regimens for metastatic colorectal cancer show that bevacizumab(Drug information on bevacizumab) (Avastin) can be safely added to oxaliplatin(Drug information on oxaliplatin) (Eloxatin)/ fluoropyrimidine regimens and that the addition significantly improves response rates. Howard S. Hochster, MD, of New York University School of Medicine, reported the early results of TREE-2 at the 2005 Gastrointestinal Cancers Symposium (abstract 241). The TREE-2 study is a continuation of TREE-1, which is a randomized phase II study of three oxaliplatin/ fluoropyrimidines regimens (see Table 1). After publication of studies showing that adding bevacizumab improves survival of patients treated with irinotecan(Drug information on irinotecan) (Camptosar)/5-FU/LV (IFL) by about 35% (N Engl J Med 350:2335- 2342, 2004), the TREE-1 protocol was amended in November 2003 to add bevacizumab to all three regimens. "This randomized, multicenter study is the first to determine the safety and tolerability of oxaliplatin/fluoropyrimidine regimens (bolus, infusional, and oral) in combination with bevacizumab for first-line treatment of metastatic colorectal cancer," Dr. Hochster said. The study enrolled patients with measurable, untreated metastatic colorectal cancer and ECOG performance status of 1 or lower. The primary endpoint was incidence of grade 3-4 toxicities on each arm during the first 12 weeks of therapy. Dr. Hochster reported that 223 patients were accrued between November 2003 and March 2004 in TREE-2, of whom 213 were treated. He reported toxicity data for 71 patients treated with FOLFOX-bevacizumab (FOLFOX- B), 70 treated with bFOL-B, and 72 treated with CapeOx-B. "Addition of bevacizumab to all regimens was well tolerated, and no significant additive toxicities were noted," he said. Dr. Hochster noted that compared with TREE-1, CapeOx tolerability improved on TREE-2 with a lower capecitabine(Drug information on capecitabine) dose of 850 mg/m² twice daily (vs 1,000 mg/m² twice daily on TREE- 1), with no decrease in efficacy. Based on a preliminary analysis of response data in the TREE-2 cohort, Dr. Hochster and his colleagues found that FOLFOX-B appears to be more active than bFOL-b, and that FOLFOX- B and CapeOx-B are approximately equivalent in efficacy (see Table 2)