A Phase I & Pharmacologic Trial Of Sequential Irinotecan As A 24-Hour IV Infusion, Leucovorin, & Flurouracil As A 48-Hour IV Infusion In Adult Cancer Patients
- Determine the recommended phase II dose of irinotecan, leucovorin calcium, and
fluorouracil in patients with advanced solid tumors.
- Determine the toxic effects of this regimen in these patients.
- Determine the pharmacokinetic and pharmacodynamic profiles of irinotecan and
fluorouracil in patients treated with this regimen.
- Determine the correlation of polymorphisms in the promoter region of the thymidylate
synthase gene with clinical toxicity and response in patients treated with this
- Determine the correlation of polymorphisms in the uridine diphosphate
glucuronosyltransferase 1A1 gene promoter with the extent of SN-38 glucuronidation and
severity of diarrhea in patients treated with this regimen.
- Assess any anti-tumor activity of this regimen in these patients.
OUTLINE: This is a dose-escalation study of irinotecan and fluorouracil.
Patients receive irinotecan IV continuously over 24 hours on days 1 and 15 and leucovorin
calcium IV over 30 minutes followed by fluorouracil IV continuously over 48 hours on days 2
and 16. Treatment repeats every 28 days for at least 2 courses in the absence of disease
progression or unacceptable toxicity.
Cohorts of 3-6 patients receive escalating doses of irinotecan until the maximum tolerated
dose (MTD) is determined. Once the MTD of irinotecan has been determined, additional cohorts
receive escalating doses of fluorouracil until the MTD is determined. The MTD is defined as
the dose preceding that at which 2 of 3 or 2 of 6 patients experience dose-limiting
PROJECTED ACCRUAL: Approximately 40 patients will be accrued for this study within 20
Primary Purpose: Treatment
Eva Szabo, MD
National Cancer Institute (NCI)
United States: Federal Government
|Warren Grant Magnuson Clinical Center - NCI Clinical Studies Support||Bethesda, Maryland 20892-1182|