A phase I trial of docetaxel and gemcitabine in patients with advanced cancer

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.

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.

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.

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.