Phase I Trial of Irinotecan, Cisplatin, and Fluorouracil in Patients With Advanced Solid Tumor Malignancies

OBJECTIVES: I. Determine the maximum tolerated dose of weekly irinotecan in combination with weekly fluorouracil and cisplatin in patients with locally advanced or metastatic solid tumors. II. Determine the dose limiting toxicity for this combination regimen in this patient population. III. Establish a recommended phase II dose for this combination regimen in these patients. IV. Evaluate the safety and tolerability of this regimen in these patients. V. Observe any responses to this combination chemotherapy in these patients. VI. Measure in pretreatment biopsies levels of expression of thymidylate synthase, topoisomerase I, ERCC-1, thymidine phosphorylase, and dihydropyrimidine dehydrogenase as correlates to response or resistance to this combination chemotherapy in these patients.

OUTLINE: This is a dose escalation study of irinotecan and fluorouracil. Patients receive cisplatin IV over 30 minutes followed by fluorouracil IV over several minutes followed by irinotecan IV over 30 minutes on days 1, 8, 15, and 22. Treatment continues every 6 weeks in the absence of unacceptable toxicity or disease progression for a minimum of 3 courses. Cohorts of 3-6 patients receive escalating doses of irinotecan and fluorouracil until the maximum tolerated dose (MTD) of each is determined. The MTD is defined as the dose preceding that at which 2 of 3 or 2 of 6 patients experience dose limiting toxicities. Patients are followed at 30 days and then until death.

PROJECTED ACCRUAL: A total of 3-36 patients will be accrued for this study within 1-2 years.