A Phase I Study of Low Dose Continuous Infusion Topotecan in Combination With 5-Fluorouracil and Leucovorin for Advanced Malignancies
OBJECTIVES: I. Evaluate the maximum tolerated dose (MTD) of continuous infusion topotecan in
combination with fluorouracil for patients with advanced malignancy and establish a
recommended phase II dose based on the MTD. II. Evaluate the dose limiting toxicity of this
combination in these patients. II. Obtain pharmacokinetic and pharmacodynamic data for
topoisomerase-1 depletion in patients receiving this treatment. IV. Identify any objective
tumor responses arising from this treatment in these patients.
OUTLINE: This is a dose-escalation study of topotecan in combination with fluorouracil.
Patients receive topotecan as a 24-hour continuous infusion on days 1-14 in combination with
fluorouracil IV and leucovorin calcium IV on days 1-5; course repeats every 4 weeks.
Treatment continues in the absence of unacceptable toxicity or disease progression. In the
absence of dose limiting toxicity (DLT) in the first cohort of 3 patients treated,
subsequent cohorts each receive escalating doses on the same schedule. If DLT is observed in
2 of 3 patients or 2 of 6 patients at a given dose level, then dose escalation ceases and
the next lower dose is declared the maximum tolerated dose.
PROJECTED ACCRUAL: Approximately 6-30 patients will be accrued for this study.
Primary Purpose: Treatment
Howard S. Hochster, MD
New York University School of Medicine
United States: Federal Government
|Kaplan Cancer Center||New York, New York 10016|