Résumé
Abstract only e15075
Background: Oral fluoropyrimidines, notably capecitabine, are increasingly replacing IV 5-FU/LV as the backbone of therapy for metastatic colorectal cancer. The bi-weekly combination of capecitabine/irinotecan warrants further examination. Methods: We conducted a phase I trial, in metastatic cancer patients treated for solid tumors, to determine the recommended dose of capecitabine administered orally bid from day 1 to 8 in combination with a bi-weekly fixed-dose of IV irinotecan 180 mg/m
2
delivered on day 1 and 14 (FIRST STAGE: XELIRI); and + a bi-weekly fixed-dose of IV oxaliplatin (L-OHP) 85 mg/m
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delivered on day 1 and 14 (Second STAGE: XELIRINOX). Five increasing dose levels (DL1–5) of capecitabine were planned: 1000, 1250, 1500, 1750, and 2000 mg/m
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bid. A pharmacokinetic study of this association was performed. Results: In the first stage, a total of 17 patients were enrolled, with a median age of 60 (range 52–73) years. All patients had an ECOG PS of either 0 (59%), 1 (35%), or 2 (6%). Four patients experienced dose-limiting toxicity: 2 developed grade 4 neutropenia (at DL 1 and 4) and 2 others grade 4 febrile neutropenia (at DL3 and 4). One toxicity-related death occurred following febrile neutropenia (DL4). Maximal tolerated dose (MTD) was DL4, and the recommended dose regimen was bi-weekly irinotecan 180 mg/m
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combined with capecitabine 1500 mg/m
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bid (administered from days 1 to 8). In the second stage, the starting dose level of capecitabine in the bi- weekly association with irinotecan and L-OHP was defined as two dose levels below the MTD level reached in the first stage of the study (DL4 - 2 = DL2). Height patients were enrolled with a median age of 56 (35–75) and ECOG 0 for 62%, ECOG 1 for 38%. Chemotherapy is ongoing for three of them. Three patients experienced dose-limiting toxicity: 1 grade 4 neutropenia ( DL2), 1 grade 4 febrile neutropenia ( DL3) and 1 grade 4 pneumopathy ( DL3). The MTD of XELIRINOX was DL3, and the recommended dose regimen will be presented at the meeting. Conclusions: Bi-weekly combination of capecitabine/irinotecan/oxaliplatin (XELIRI / XELIRINOX) is feasible and could be tested in patients with metastatic colorectal cancer in combination with a targeted therapy.
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