A phase I trial of docetaxel and gemcitabine in patients with advanced cancer.
BACKGROUND
Docetaxel and gemcitabine are active in a broad range of malignancies. The objective of this phase I trial was to determine the maximally tolerated doses of the combination of docetaxel and gemcitabine.


METHODS
Patients with advanced cancer, WHO performance status 0-2, who had received up to one prior chemotherapy regimen were treated with gemcitabine on days 1 and 8 and docetaxel on day 8 repeated every 21 days. Prophylactic ciprofloxacin was commenced on day 11 of each cycle and continued until the neutrophil count reached 1.0 x 10(9)/l. G-CSF was not administered. Dose levels studied were docetaxel/gemcitabine: 60/800, 60/1000, 75/1000, 75/1200, 85/1200 and 100/1200 mg/m2.


RESULTS
Thirty-nine patients were entered and all were assessable for toxicity. The highest administered dose level was 100 mg/m2 docetaxel and 1200 mg/m2 gemcitabine with dose limiting toxicities of febrile neutropenia, grade 4 neutropenia > or = 7 days, grade 4 thrombocytopenia, grade 3 stomatitis and/or grade 3 fatigue in three out of six patients. Treatment was well tolerated (40 cycles) in the 10 patients treated at the recommended dose level (85/1200) with only a single episode of febrile neutropenia and grade 3 or 4 non-hematologic toxicity was infrequent. There was no significant pulmonary toxicity. Responses were seen in a range of malignancies including non-small-cell lung cancer.


CONCLUSIONS
The recommended dose level of 85 mg/m2 docetaxel and 1200 mg/m2 gemcitabine has a favourable toxicity profile and is suitable for further investigation in phase II trials. This non-platinum containing regimen warrants further investigation as a potential alternative to platinum containing regimens in non-small-cell lung cancer and other malignancies.
Rischin
D
D
Division of Haematology and Medical Oncology, Peter MacCallum Cancer Institute, Melbourne, Australia. drischin@petermac.unimelb.edu.au
Boyer
M
M
Smith
J
J
Millward
M
M
Michael
M
M
Bishop
J
J
Zalcberg
J
J
Davison
J
J
Emmett
E
E
McClure
B
B
D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy; D003841:Deoxycytidine / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives; D000077143:Docetaxel; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy; D008297:Male; D008875:Middle Aged; D009369:Neoplasms / Q000188:drug therapy*; D017239:Paclitaxel / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives; D043823:Taxoids; D016896:Treatment Outcome; D000093542:Gemcitabine
D043823:Taxoids; D003841:Deoxycytidine; D000077143:Docetaxel; D017239:Paclitaxel; D000093542:Gemcitabine