Phase I trial of gemcitabine and CPT-11 given weekly for four weeks every six weeks

Background: Our previous studies have shown that the in vitro cytotoxicity of gemcitabine and SN-38, the active metabolite of irinotecan (CPT-11), is synergistic in human tumor cell lines. Patients and methods: Twenty-four patients with solid tumors, refractory to standard chemotherapy or for whom no effective therapy existed (age range 31-74; 7 female, 17 male; ECOG PS 0 = 12, 1 = 11, 2 = 1), received gemcitabine and CPT-11 weekly for four weeks out of every six weeks. Fifty courses of treatment (median 2, range 1-8) were given through five dose levels of gemcitabine/CPT-11 (600/75, 800/75, 800/100, 1000/100, 1000/125 mg/m(2)). Results: Grade 3 and 4 neutropenia occurred in eight and two patients, respectively. Grade 3 and 4 thrombocytopenia occurred in one and three patients, respectively. Hematologic toxicity resulted in greater than or equal to2 missed doses of treatment in two out of six patients and was therefore dose limiting at gemcitabine 1000 mg/m(2) and CPT-11 125 mg/m(2). Grade 3 and 4 diarrhea occurred in two and one patients, respectively. Other moderate non-hematologic toxicities included alopecia, anorexia, fatigue, nausea, vomiting, and weight loss. Conclusions: The maximum tolerated dose for this study recommended for phase II testing is gemcitabine 1000 mg/m(2) and CPT-11 100 mg/m(2). A partial response was seen in transitional cell carcinoma.