A phase I study of gemcitabine, 5-fluorouracil and leucovorin in patients with advanced, recurrent, and or metastatic solid tumors

Introduction: This was a dose escalation phase I trial designed to establish the MTD (maximum tolerated dose) and toxicity profile of the combination of gemcitabine, leucovorin and 5-fluorouracil (5-FU). Methods: Standard eligibility criteria were required for patients with advanced malignancy to enrol. Gemcitabine was escalated from an initial dose of 800 mg/m(2.) Gemcitabine was administered prior to leucovorin (25 mg/m(2)) followed by bolus 5-FU (600 mg/m(2)) every week for 3 weeks followed by 1 week of rest. Results: Of 21 patients enrolled, 20 were eligible for MTD determination. Patients received a median of three 4-week cycles of chemotherapy (range: 1 to 8 cycles). Toxicity was predominantly hematologic or gastroenterologic. Four dose levels were studied. At a gemcitabine dose of 1,500 mg/m(2) systemic symptoms of fatigue accompanied hematologic toxicity and patients refused further therapy. At 1,250 mg/m(2), full dose intensity was not delivered during the first cycle in 7 of 8 patients treated. Therefore, 1,000 mg/m(2) was established as the recommended phase II dose for gemcitabine in this study. Antitumor activity was seen at all dose levels. Conclusions: The combination of gemcitabine, leucovorin and 5-FU was tolerable at full doses of all 3 drugs with an expected toxicity profile. Recommended phase II dose for gemcitabine was 1,000 mg/m(2). Initial evidence of clinical activity was seen in a variety of tumor types.