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

Authors: Berlin J.D.; Alberti D.B.; Arzoomanian R.Z.; Feierabend C.A.; Simon K.J.; Binger K.A.; Marnocha R.M.; Wilding G.

Source: Investigational New Drugs, Volume 16, Number 4, 1998 , pp. 325-330(6)

Publisher: Springer

Abstract:

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^2systemic 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.

Keywords: gemcitabine; 5-fluorouracil; leucovorin; phase I study

Language: English

Document Type: Regular paper

Affiliations: 1: Division of Oncology, University of Wisconsin, WI, USA

Publication date: 1998-01-01

• In this: publication
• By this: publisher
• In this Subject: Oncology ,  Pharmacology
• By this author: Berlin J.D. ;  Alberti D.B. ;  Arzoomanian R.Z. ;  Feierabend C.A. ;  Simon K.J. ;  Binger K.A. ;  Marnocha R.M. ;  Wilding G.

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