[Oxaliplatin in combination with 5-fluoro-uracil and folinic acid as treatment of metastatic colorectal cancer].
Unusual aspect of the development of oxaliplatin was that substantial evidence of its activity was gathered when used in combination with protracted infusion of 5FU combined with leucovorin, preceeding the formal demonstration of its single activity in this disease. Phase II trials in previously treated patients by 5FU, have shown response rate of 10% with oxaliplatin in monotherapy and 18,4 to 58% with chronomodulated or bimonthly regimen combining oxaliplatin, 5FU and leucovorin. These trials have confirmed additive or synergistic antitumoral effects of this combination. Dose intensity of oxaliplatin may be important in determining the efficacy of the triple agent regimen. For previously untreated patients, Folfox4 (LV5FU2 + 85 mg/m2 of oxaliplatin) and chronomodulated regimen have obtained objective response rate ranged from 51 to 66%, with progression-free survival between 8.2 and 11 months and overall survival from 16 to 19 months. A better use of oxaliplatin in combination with 5FU and leucovorin may decrease the dose-limiting toxicity, i.e. the usually transient sensory neurotoxicity. Patients with initially unresectable metastases treated with this three-drug combination could sometimes underwent complete metastases surgery. Several studies are currently in progress either to confirm the high activity of the LV5FU-oxaliplatin combination or to define a strategy based on the best sequence or the best combinations with the other available drugs, irinotecan and raltitrexed.
André
T
T
Hôpital Tenon, 4, rue de la Chine, 75020 Paris, France.
Louvet
C
C
Maindrault-Goebel
F
F
Gramont
A D
AD
D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D019454:Chronotherapy; D017322:Clinical Trials, Phase II as Topic; D017326:Clinical Trials, Phase III as Topic; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000473:pathology; D005472:Fluorouracil / Q000008:administration & dosage / Q000009:adverse effects; D006801:Humans; D002955:Leucovorin / Q000008:administration & dosage / Q000009:adverse effects; D009944:Organoplatinum Compounds / Q000008:administration & dosage / Q000009:adverse effects; D000077150:Oxaliplatin
D009944:Organoplatinum Compounds; D000077150:Oxaliplatin; D002955:Leucovorin; D005472:Fluorouracil