A phase I study of gemcitabine and docetaxel in patients with metastatic solid tumors

BACKGROUND. A Phase I study was initiated to determine the maximum tolerate d dose of weekly gemcitabine combined with monthly, fixed-dose docetaxel. METHODS. Patients with metastatic solid tumors were treated with docetaxel, 60 mg/m(2), on Day 1 every 28 days. Gemcitabine was administered on Days 1 , 8, and 15 and underwent dose adjustment in cohorts of 3-6 patients. At th e maximum tolerated dose, 11 additional patients were enrolled. RESULTS. Twenty-six patients treated at this dose level experienced dose-li miting toxicities (DLTs) requiring the reduction of gemcitabine to 600 mg/m (2) per dose and the administration of ciprofloxacin, 500 mg orally twice d aily, on Days 8-18. At the second dose level the first 3 patients experienc ed no DLTs and the dose of gemcitabine was increased to 700 mg/m(2). Two of the 6 patients treated at the 700 mg/m(2) dose level experienced DLTs. Ele ven additional patients were enrolled at the recommended Phase II dose of g emcitabine (600 mg/m(2)). At this dose level, Grade 3/4 (according the Nati onal Cancer Institute's common toxicity criteria) neutropenia and thrombocy topenia occurred in 12.5% and 2.1% of cycles, respectively. Grade 3 and 4 n onhematologic toxicities were uncommon. Three of seven evaluable patients w ith pancreatic carcinoma had evidence of significant antineoplastic activit y (three partial responses). In addition, two complete responses (one patie nt with gastric carcinoma and one patient with ovarian carcinoma) and one p artial response (patient with hepatocellular carcinoma) were noted in patie nts with other solid tumors. CONCLUSIONS. The regimen comprised of docetaxel, 60 mg/m(2), on Day 1 and g emcitabine, 600 mg/m(2), on Days 1, 8, and 15 with ciprofloxacin on Days 8- 18 every 28 days is safe, well tolerated, and active. Cancer 2000;88:180-5. (C) 2000 American Cancer Society.