Can inhibition of angiogenic pathways increase the efficacy of intravenous 5-fluorouracil-based regimens?
First-line irinotecan-containing regimens are toxic and may not be tolerated well by all patient subgroups. Trials evaluating less toxic regimens include a randomized, double-blind, multicenter study (AVF2192g) assessing 5-fluorouracil (5-FU)/leucovorin (LV) with bevacizumab. Patients were randomized to 1 of 2 treatment arms. In arm 1, patients received LV intravenously (I.V.) over 2 hours and 5-FU I.V. over 1 hour every week for 6 weeks of an 8-week cycle, and bevacizumab 5 mg/kg was administered I.V. over 30-90 minutes every 2 weeks. In the second arm, patients received LV and 5-FU as in arm 1, and placebo I.V. over 30-90 minutes every 2 weeks. The primary objective was duration of survival. Eligible patients with untreated metastatic colorectal cancer (CRC) were >or= 65 years of age, had an Eastern Cooperative Oncology Group performance status of 1/2, a serum albumin level <or= 3.5 g/dL, or had previous radiation therapy to the pelvis or abdomen. Preliminary results indicated a median survival of 12.9 months versus 16.6 months on the placebo and bevacizumab arms, respectively (P = 0.159). Progression-free survival was 5.5 months in the placebo arm compared to 9.2 months in the bevacizumab arm. The overall response rate was 15% in the placebo arm and 26% in the bevacizumab arm. The percentages of patients experiencing toxicities typically associated with 5-FU/LV were similar in both arms. Toxicities most associated with bevacizuamb included bleeding, thrombolic events, hypertension, and proteinuria. Growing evidence indicates that bevacizumab is an effective agent in CRC when added to several chemotherapy combinations. The current study indicates that subpopulations of patients with advanced age or poor performance status could be treated successfully with 5-FU/LV in combination with bevacizumab without excessive toxicities.
Division of Hematology/Oncology, Department of Medicine, 10945 Le Conte Ave, University of California Los Angeles 2338 John, PVUB MC, 718707, Los Angeles, CA 90095-7187, USA. fkabbina@mednet.ucla.edu.
Fairooz F
FF
Kabbinavar
Lee M
LM
Ellis
D000328:Adult; D000368:Aged; D020533:Angiogenesis Inhibitors / Q000008:administration & dosage; D000911:Antibodies, Monoclonal / Q000008:administration & dosage; D061067:Antibodies, Monoclonal, Humanized; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D000068258:Bevacizumab; D017322:Clinical Trials, Phase II as Topic / Q000379:methods*; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000401:mortality* / Q000473:pathology; D018572:Disease-Free Survival; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage; D005500:Follow-Up Studies; D006801:Humans; D007262:Infusions, Intravenous; D008297:Male; D020714:Maximum Tolerated Dose; D008875:Middle Aged; D009367:Neoplasm Staging; D009389:Neovascularization, Pathologic / Q000517:prevention & control; D016032:Randomized Controlled Trials as Topic / Q000379:methods*; D018570:Risk Assessment; D016019:Survival Analysis; D016896:Treatment Outcome
D020533:Angiogenesis Inhibitors; D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D000068258:Bevacizumab; D005472:Fluorouracil