A phase I and pharmacokinetic study of the combination of capecitabine and docetaxel in patients with advanced solid tumours.
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).
Pronk
L C
LC
Rotterdam Cancer Institute (Daniel den Hoed Kliniek) and University Hospital, The Netherlands.
Vasey
P
P
Sparreboom
A
A
Reigner
B
B
Planting
A S
AS
Gordon
R J
RJ
Osterwalder
B
B
Verweij
J
J
Twelves
C
C
D000328:Adult; D000368:Aged; D000505:Alopecia / Q000139:chemically induced; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D001247:Asthenia / Q000139:chemically induced; D001711:Biotransformation; D000069287:Capecitabine; D002265:Carboxylic Ester Hydrolases / Q000378:metabolism; D003641:Deamination; D003841:Deoxycytidine / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives / Q000493:pharmacokinetics; D003907:Dexamethasone / Q000008:administration & dosage; D000077143:Docetaxel; D004334:Drug Administration Schedule; D005260:Female; D005334:Fever / Q000209:etiology; D005472:Fluorouracil / Q000378:metabolism; D005767:Gastrointestinal Diseases / Q000139:chemically induced; D006801:Humans; D007262:Infusions, Intravenous; D008099:Liver / Q000201:enzymology; D008297:Male; D020714:Maximum Tolerated Dose; D008775:Methylprednisolone / Q000008:administration & dosage; D008875:Middle Aged; D009369:Neoplasms / Q000188:drug therapy* / Q000473:pathology; D009503:Neutropenia / Q000139:chemically induced; D017239:Paclitaxel / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives / Q000493:pharmacokinetics; D010304:Paronychia / Q000139:chemically induced; D011355:Prodrugs / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics; D012074:Remission Induction; D043823:Taxoids; D016896:Treatment Outcome
D011355:Prodrugs; D043823:Taxoids; D003841:Deoxycytidine; D000077143:Docetaxel; D000069287:Capecitabine; D003907:Dexamethasone; D002265:Carboxylic Ester Hydrolases; D017239:Paclitaxel; D005472:Fluorouracil; D008775:Methylprednisolone