Phase I trial of irinotecan, infusional 5-fluorouracil, and leucovorin (FOLFIRI) with erlotinib (OSI-774): early termination due to increased toxicities

Advanced colorectal cancer.

To establish the dose-limiting toxicities and maximum-tolerated dose of erlotinib, an
oral epidermal growth factor receptor tyrosine kinase inhibitor, in combination with
FOLFIRI, a standard regimen of irinotecan, leucovorin, and infusional 5-fluorouracil
(5-FU) in patients with advanced colorectal cancer.

Official Title

Conditions

Study Type

Phase I

Study Design

Treatment Details:Erlotinib 100 mg/d p.o. continuously. and dose reducedFOLFORIIrinotecan: 150mg/m2 i.v. d1Leucovorin: 200mg/m2 i.v. 5-FU: 320mg/m2 i.v. bolus d1-25-FU: 480mg/m2 i.v. cont. inf. (22h) d1-2administered in 6-week cycles (three FOLFORI treatments)Efficacy: Response after cycle 1SD: 5 (83%)PR: 1 (17%), unconfirmedTolerability: The trial was stopped at the lowest dose level because of excessive toxicity (despite supportive measures):Disfiguring grade 2 rash (3)Grade 3 diarrhea (4)Grade > 3 neutropenia (3)Pulmonary embolism (1)Conclusions from the Authors: FOLFIRI combined with erlotinib causes excessive toxicity at reduced doses. These findings contrast with available data regarding the optimal safety profile of trials combining small molecule epidermal growth factor receptor inhibitors with other conventional chemotherapy and highlight the need to perform safety-oriented studies of such combinations.Comments from Baxter Oncology: No plasma pharmacokinetic interaction was observed that could explain the observed increased toxicity. A response rate of 78% has been reported in a phase II study combining the EGFR inhibitor gefitinib with FOLFOX-4 in the first-line setting with no significant increase of toxicity.

Further Details

Study Start

Eligibility & Criteria

Histologically confirmed advanced colorectal adenocarcinoma; no previous treatment;age > 18 years; ECOG PS: 0-1; adequate organ and bone marrow functions.

Total Enrolment

6

Contact Details

Clinical Cancer Research 10 (2004): 6522-6527Baxter