The goals of this study are to determine the maximum tolerable dose of gemcitabine given as a 30-minute infusion weekly for three weeks followed by one week rest; to determine the toxicities of gemcitabine given on this schedule; to determine the pharmacokinetic behavior of gemcitabine in male and female patients; and to determine the antitumor activity of gemcitabine within the confines of a phase I study. The study was opened to patient entry in July 1996. Fifteen eligible patients have received 27 courses: 6 patients at 1000 mg/m2 weekly times 3 and 7 patients at 1200 mg/m2 weekly times 3. One patient at each drug level had been heavily pretreated with chemotherapy and radiotherapy. They experienced grade 4 myelosuppression and did not receive the third dose. Another patient at the 1200 mg/m2 dose level experienced grade 3 LFT abnormalities so a dose was held and a third dose3 was given at a lower dose. Myelosuppression has been reported as expected; at 1000 mg/m2, grade 4 toxicity was leukopenia in three patients, and thrombocytopenia in two patients. These are transient, only one of six patients at 1000 mg/m2 weekly times 3 had dose-limiting toxicity. At 1200 mg/m2, two of seven patients were not evaluable and one is too early. Grade 4 neutropenia has not been reported, and only one patient had grade 4 thrombocytopenia. Dose-limiting toxicity has not been reported. Future plans are to continue pharmacokinetic sampling on both girls and boys to see if sex differences found in adults can be confirmed. It is likely that the study will explore the next drug level.
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