ISSN:
1569-8041
Keywords:
adjuvant chemotherapy schedule
;
colorectal cancer
;
5-fluorouracil
;
folinic acid
;
randomised controlled trial
Source:
Springer Online Journal Archives 1860-2000
Topics:
Medicine
Notes:
Abstract Background:QUASAR is a large trial of adjuvant chemotherapy forcolorectal cancer in which clinicians could choose to deliver a standardadjuvant cytotoxic chemotherapy regimen, 5-fluorouracil (5-FU) and L-folinicacid (L-FA), in either a once-weekly or a four-weekly schedule. We reportresults of a non-randomised comparison between these schedules with respectto survival, recurrence and differential toxicity. Patients and methods:In a factorial (2 × 2) trial design,QUASAR compared high-dose (175 mg) versuslow-dose (25 mg) L-FA andlevamisole versusplacebo. The dose of 5-FU was fixed at 370mg/m2 and although the recommended schedule was i.v. bolusdelivery, daily for 5 days repeated four-weekly for 6 months, a significantproportion of randomising clinicians were constrained to deliver once-weekly5-FU–L-FA for 30 weeks. Results:Four thousand nine hundred twenty-seven patients wereentered into QUASAR between May 1994 and October 1997, eighteen hundredtwenty-nine of whom have recurred and sixteen hundred eighty-nine died.Similar numbers 2370 vs. 2559 were treated with the once-weekly andfour-weekly schedules and the demographic features of the 2 groups were wellbalanced: stage C, 73.3% once-weekly vs. 71.0% four-weekly;colon, 68.0% vs. 68.3%; high-dose FA, 50.1% vs.49.9%; levamisole, 49.3% vs. 49.3%; females, 40.2%vs. 41.7%; median age (years) 62 vs. 61. The risk of recurrence andsurvival were similar regardless of schedule: three-year survival was70.6% once-weekly vs. 71.0% four-weekly; three-year recurrencerisk was 35.6% once-weekly vs. 35.5% four-weekly; But, theonce-weekly regimen was much less toxic: number of patients for whom toxicitywas reported (once-weekly: four-weekly), stomatitis, 37 vs. 337; diarrhoea,260 vs. 440; neutropenia, 20 vs. 153. Conclusions:The once-weekly regimen is much less toxic than and,apparently, about as effective as the four-weekly schedule. This suggests thatthe toxicity of 5-FU–L-FA adjuvant chemotherapy could be reducedsubstantially by weekly scheduling without compromising efficacy.Alternatively, efficacy might be enhanced with equal toxicity by moredose-intense weekly FU–L-FA regimens. However, this conclusion from anon-randomised comparison needs confirmation in prospective randomisedstudies.
Type of Medium:
Electronic Resource
URL:
http://dx.doi.org/10.1023/A:1008303229469
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