A United Kingdom coordinating committee on cancer research study of adjuvant chemotherapy for colorectal cancer: preliminary results.
Standard adjuvant chemotherapy for colorectal cancer consists of 5-fluorouracil with leucovorin or levamisole. The large, multicenter, randomized, double-blind QUASAR (Quick and Simple and Reliable) trial investigated whether treatment with a higher dose of leucovorin or the addition of levamisole to 5-fluorouracil and leucovorin improved survival. In the QUASAR study, 4,927 patients with colorectal cancer with no evidence of residual disease following resection, were randomized to receive fluorouracil (370 mg/m2) with high-dose (175 mg) or low-dose (25 mg) leucovorin and either levamisole (50 mg) or placebo. The fluorouracil and leucovorin regimen was given either monthly (as six 5-day courses with 4 weeks between the start of each course) or weekly (as 30 once-weekly doses). Levamisole or placebo was given three times daily for 3 days, repeated every 2 weeks for 12 courses. The primary endpoint was death from any cause. Survival was similar with both high- and low-dose leucovorin (70.1% v 71.0% at 3 years; P = .43) as well as recurrence rates (36.0% v 35.8%; P = .94), and with levamisole compared with placebo (69.4% v 71.5%; P = .06) as well as recurrence rates (37.0% v 34.9%; P = .16). Monthly and weekly treatments were equally effective (although this was a nonrandomized comparison), while weekly treatment was associated with significantly fewer toxic effects (neutropenia, mucositis, and diarrhea). High-dose leucovorin was not associated with a survival or recurrence benefit when compared with low-dose leucovorin. The ongoing QUASAR-1 trial aims to establish whether adjuvant chemotherapy has any worthwhile survival benefit in colorectal cancer patients with an uncertain indication following surgical resection.
University of Birmingham, CRC Institute for Cancer Studies, Edgbaston, UK.
D J
DJ
Kerr
D000276:Adjuvants, Immunologic / Q000008:administration & dosage / Q000627:therapeutic use*; D000368:Aged; D000964:Antimetabolites, Antineoplastic / Q000627:therapeutic use*; D017024:Chemotherapy, Adjuvant; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000601:surgery; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D005260:Female; D005472:Fluorouracil / Q000627:therapeutic use*; D006801:Humans; D002955:Leucovorin / Q000008:administration & dosage / Q000627:therapeutic use*; D007978:Levamisole / Q000008:administration & dosage / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local; D016017:Odds Ratio; D011446:Prospective Studies
D000276:Adjuvants, Immunologic; D000964:Antimetabolites, Antineoplastic; D007978:Levamisole; D002955:Leucovorin; D005472:Fluorouracil