Cisplatin plus weekly CPT11/docetaxel in advanced esophagogastric cancer: a phase I study with pharmacogenetic assessment of XPD, XRCC3 and UGT1A1 polymorphisms (original) (raw)

Cancer Chemotherapy and Pharmacology, 2008

Abstract

Purpose A multicenter phase I trial to establish the recommended dose of CPT-11/docetaxel plus cisplatin in advanced esophagogastric cancer patients and to correlate the efficacy and toxicity with genetic polymorphisms in DNA repair genes (XPD and XRCC3) and the UGT1A1 gene. Methods Four dose levels with a fixed dose of cisplatin (60 mg/m2), day 1, and dose-escalation of CPT-11 (50–70 mg/m2) and docetaxel (25–30 mg/m2), days 1 and 8, every 3 weeks were planned. Polymorphisms of XPD (Asp312Asn and Lys751Gln), XRCC3 (Thr241Met) and UGT1A1*28 were examined in baseline peripheral blood. Results Twenty-eight patients were included at three different dose levels. Dose-limiting toxicities were febrile neutropenia and diarrhea; the recommended dose was established at CPT-11 60 mg/m2 and docetaxel 25 mg/m2 plus cisplatin 60 mg/m2. Objective response was observed in 13 patients (50%). Median time to progression was 6.6 months, and median survival was 11.3 months. Median time to progression was 9.7 months for patients harboring the XRCC3 Met241Met genotype versus 8.4 months for patients with Thr241Met and 3.1 months for those with Thr241Thr (P = .04). Conclusions CPT-11/docetaxel plus cisplatin is active in patients with advanced esophagogastric cancer. XRCC3 Met241Thr polymorphisms could be a useful marker to predict prognosis in patients treated with a cisplatin-based chemotherapy. However, these results are required to be confirmed with a great number of patients.

JOSE LUIS RAMIREZ hasn't uploaded this paper.

Let JOSE LUIS know you want this paper to be uploaded.

Ask for this paper to be uploaded.