| Autor: |
Lèvi, F., Machover, D., Marty, M., Diaz-Rubio, E., de Gramont, A., Garufi, C., Itzhaki, M., Cvitkovic, E., Bensmaïne, M.A., Brienza, S., Misset, J.L. |
| Zdroj: |
European Journal of Cancer; November 1995, Vol. 31 Issue: 6 pS154-S154, 1p |
| Abstrakt: |
Standard treatment of ACC consists of a combination of 5-fluorouracil (5-FU) will folinic acid (FA). No other cytotoxic agents tested so far showed therapeutic benefit in the treatment of ACC. L-OHP®showed activity in 6/8 colon cancer lines in the NC1 compare screen. It was tested after an in vivo(L1210) demonstration of synergistic effect with 5-FU and the observation of one partial response in a phase 1 study. Nine clinical trials with L-ODHP®(2 hr bolus or 5–day flat (F) or chronomulated (CM) infusion) in 582 pts with ACC have been conducted between 03/88 and 06/94: 3 phase II in monotherapy (138 pts), 4 phase II (159 pts) and 2 phase III (278 pts) in combination with 5-FU/FA. Significant results observed are:• The toxicologic profile of L-OHP®(no renal or hematologic toxicity) allowed a safe association with 5-FU and FA.• Peripheral sensitive neuropathy was dose-limiting: grade III (functional impairment) occurred after a median of 6 courses (780mg/sqm) in 10% of the patients. Its usual reversibility and its easy follow-up limited the extent of this drawback.• Oxaliplatin showed intrinsic activity in pretreated and 5-FU resistant ACC. The three phase II studies showed respectively 10%, 11% and 10% response rates in 29, 58 and 51 patients (14/138 with overall response rate (ORR)=10%).• Four studies, combining L-OHP with high dose 5–FU/FA (2–day q 14d F schedules or 5-day q 21d CM schedules) achieved high activity (ORR=39%—42/108 pls) in 5-FU/FA pretreated patients. PFS and survival were respectively 10 and 17 months.• In one sequential study, in 25 INS resistant (20 PD-5 SD) to CM 5-FU/FA, the addition of L-OHP7reg; induced a 29% response rate. This point suggests a clinical synergistic effect with 5-FU/FA in humans.• Clinical synergism between L-OHP®and 5-FU/FA was further suggested by a 51% ORR obtained with chronomodulated 3-day delivery in 138 pts with previously untreated metastatic colorectal cancer. In these European trials, median progression free survival and survival were respectively 10 and 17 months, and largely exceed those usually obtained with 5-FU/FA. |
| Databáze: |
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