Study of irinotecan (CPT-11) combined with fixed dose of 5-fluorouracil (5-FU) adult patients with advanced solid tumours

Advanced solid tumors (gastrointestinal incl. Colorectal, head & neck, others)

(1): to find the maximum tolerated dose (MTD) of the combined chemotherapy. (2): to
determine the quantitive and qualitative toxic effects, the Dose-limiting toxicity and the
recommended dose for phase II trials. (3): to define the safety profile of this
combination. (4): to investigate if any antitumor activity could be documented and (5):
to determine the pharmacokinetic parameters of CPT-11 and 5-FU and their
metabolites.

Official Title

A phase I, dose-finding study of irinotecan (CPT-11) short i.v. infusion combined withfixed dose of 5-fluorouracil (5-FU) protracted i.v. infusion in adult patients withadvanced solid tumours

Conditions

Study Type

Phase I pharmacokinetic and clinical study

Study Design

Further Details

Treatment Details:Step 1CPT-11 150mg/m2 (175, 200, 250, 300, 350 mg/m2 ) i.v. (90 min) d1 every 3 weeks.5-FU 250 mg/m2/d cont. inf. over 14 days using a portable infusion device.if the MTD was not reached at CPT-11 dose level 6, the 5-FU dose was increased to300 mg/m2 at dose level 7Step 2CPT-11 300 mg/m2 i.v. (90 min) d1 every 3 weeks.5-FU 250 mg/m2 administered as true protracted for 3 weeks without break.Step 3CPT-11 75 mg/m2 weekly for 4 weeks5-FU CI 250 mg/m2 for 4 weeks followed by 2-5 weeks of rest.Efficacy:47 patients evaluable (treated in all steps)Objective response 11 (23.4%), incl. 8/22 (36.4%) with colorectal cancer.Tolerability: safety:Grade 3 / 4 toxicity during step 1Neutropenia (gr.4) 2 (6.5%)Diarrhea 3 (9.7%)Vomiting 2 (6.5%)Nausea 1 (3.2%)Asthenia 1 (3.2%)Mucositis 2 (6.5%)Neurological symptoms 1 (3.2%)Conclusions from the Authors:No interactions were found in the kinetics parameters of CPT-11 or 5-FU for the different dose levels studied. CPT-11 300 mg/m2 + 5-FU 250 mg/m2 protracted infusion is the recommended dose for phase II trials, neutropenia and diarrhoea being the dose-limiting toxicities.

Study Start

Eligibility & Criteria

Histologically proven advanced solid tumor; Age 18-70 years; failure of previously -standard treatment or lack of curative therapy; WHO PS < 2; satisfactory renal andliver functions.

Total Enrolment

54 (42 for pharmacokinetic analysis)

Contact Details

Cancer Chemotherapy and Pharmacology, prepublished online: October 2004Baxter