A phase I and pharmacokinetic study of the combination of capecitabine and docetaxel in patients with advanced solid tumours

Abstract

Capecitabine and docetaxel are both active against a variety of solid tumours, while their toxicity profiles only partly overlap. This phase I study was performed to determine the maximum tolerated dose (MTD) and side-effects of the combination, and to establish whether there is any pharmacokinetic interaction between the two compounds. Thirty-three patients were treated with capecitabine administered orally twice daily on days 1-14, and docetaxel given as a 1 h intravenous infusion on day 1. Treatment was repeated every 3 weeks. The dose of capecitabine ranged from 825 to 1250 mg m-2 twice a day and of docetaxel from 75 to 100 mg m-2. The dose-limiting toxicity (DLT) was asthenia grade 2-3 at a dose of 1000 mg m-2 bid of capecitabine combined with docetaxel 100 mg m-2. Neutropenia grade 3-4 was common (68% of courses), but complicated by fever in only 2.4% of courses. Other non-haematological toxicities were mild to moderate. There was no pharmacokinetic interaction between the two drugs. Tumour responses included two complete responses and three partial responses. Capecitabine 825 mg m-2 twice a day plus docetaxel 100 mg m-2 was tolerable, as was capecitabine 1250 mg m-2 twice a day plus docetaxel 75 mg m-2. (C) 2000 Cancer Research Campaign.