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).
Publication types
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Clinical Trial
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Clinical Trial, Phase I
MeSH terms
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Adult
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Aged
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Alopecia / chemically induced
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Antineoplastic Combined Chemotherapy Protocols / administration & dosage
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Antineoplastic Combined Chemotherapy Protocols / adverse effects
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Antineoplastic Combined Chemotherapy Protocols / pharmacokinetics
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Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
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Asthenia / chemically induced
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Biotransformation
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Capecitabine
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Carboxylic Ester Hydrolases / metabolism
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Deamination
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Deoxycytidine / administration & dosage
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Deoxycytidine / adverse effects
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Deoxycytidine / analogs & derivatives
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Deoxycytidine / pharmacokinetics
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Dexamethasone / administration & dosage
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Docetaxel
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Drug Administration Schedule
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Female
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Fever / etiology
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Fluorouracil / metabolism
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Gastrointestinal Diseases / chemically induced
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Humans
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Infusions, Intravenous
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Liver / enzymology
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Male
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Maximum Tolerated Dose
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Methylprednisolone / administration & dosage
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Middle Aged
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Neoplasms / drug therapy*
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Neoplasms / pathology
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Neutropenia / chemically induced
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Paclitaxel / administration & dosage
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Paclitaxel / adverse effects
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Paclitaxel / analogs & derivatives
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Paclitaxel / pharmacokinetics
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Paronychia / chemically induced
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Prodrugs / administration & dosage
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Prodrugs / adverse effects
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Prodrugs / pharmacokinetics
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Remission Induction
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Taxoids*
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Treatment Outcome
Substances
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Prodrugs
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Taxoids
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Deoxycytidine
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Docetaxel
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Capecitabine
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Dexamethasone
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Carboxylic Ester Hydrolases
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Paclitaxel
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Fluorouracil
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Methylprednisolone