Oxaliplatin plus 5-fluorouracil: clinical experience in patients with advanced colorectal cancer.
Oxaliplatin was first introduced to the clinical setting as a combination therapy with 5-fluorouracil/folinic acid (5-FU/FA) in an attempt to improve the response rate obtained with 5-FU/FA against colorectal cancer. To dispel the impression that the improvements observed in objective response were somehow due to the chronomodulated regimen used, oxaliplatin was also tested in constant-rate infusion schedules and in regimens using bolus administration followed by 5-FU/FA infusion. The most current data comparing chronomodulated infusion and constant-rate infusion in untreated patients show a lower objective response rate for the latter (51 % v 29%), but comparable median progression-free survival and median survival (9.8 months and 15.9 months v 7.9 months and 16.9 months, respectively). The first trials using constant-rate therapy included pretreated patients with metastatic colorectal cancer, most of whom were refractory to 5-FU. In these studies, conducted using two different regimens or variations of them, objective response rates < or = 46% were obtained. The addition of oxaliplatin to 5-FU/FA in controlled, randomized phase III trials has resulted in a twofold or greater increase in objective response rate and a 3-month gain in time to progression, with survival differences blurred by crossover effect. Compassionate-use programs that included many heavily pretreated relapsing patients reported response rates of 15% to 25%, confirming the value of the oxaliplatin-5-FU/FA regimen and suggesting that oxaliplatin may act synergistically with 5-FU.
Bleiberg
H
H
Unité de Chimiothérapie, Institut Jules Bordet, Bruxelles, Belgium.
de Gramont
A
A
D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D002986:Clinical Trials as Topic; D015179:Colorectal Neoplasms / Q000188:drug therapy*; D005472:Fluorouracil / Q000008:administration & dosage; D006801:Humans; D002955:Leucovorin / Q000008:administration & dosage; D009362:Neoplasm Metastasis; D009944:Organoplatinum Compounds / Q000008:administration & dosage; D000077150:Oxaliplatin
D009944:Organoplatinum Compounds; D000077150:Oxaliplatin; D002955:Leucovorin; D005472:Fluorouracil