High-dose, single-agent irinotecan as first-line therapy in the treatment of metastatic colorectal cancer.

Journal Article (Clinical Trial;Journal Article;Multicenter Study)

PURPOSE: The efficacy and safety of single-agent, high-dose irinotecan (CPT-11, Campto) 500 mg/m(2) every 3 weeks were investigated as first-line treatment for advanced colorectal cancer (CRC). PATIENTS AND METHODS: Patients were enrolled into the study to receive a first cycle of therapy with irinotecan at a dose of 350 mg/m(2) every 3 weeks, which could be escalated to 500 mg/m(2) for the second and subsequent cycles depending on toxicity. Efficacy, safety and pharmacokinetics were determined in the intent to treat (ITT) population and the high-dose population (i.e. patients who had received at least three cycles of irinotecan, the second and third at 500 mg/m(2)). RESULTS: Of 49 patients enrolled into the study (ITT population), 31 (63%) received at least three cycles of treatment with cycles 2 and 3 at an irinotecan dose of 500 mg/m(2) (the high-dose population). The response rates (RR) for the ITT and high-dose populations were 24.5% and 35.5%, respectively. The main grade 3/4 toxicities per cycle in the ITT and high-dose populations were neutropenia 22% and 17%, febrile neutropenia 5% and 3%, and diarrhoea 12% and 7%, respectively. The pharmacokinetics of irinotecan and its metabolite SN-38 were investigated in 31 patients in cycle 1 and 22 patients in cycle 2. Irinotecan clearance and SN-38 exposure were not sufficiently correlated with toxicity in cycle 1 to identify patients for dose increase in subsequent cycles. The exposure to irinotecan and SN-38 increased in proportion to dose from 350 to 500 mg/m(2). CONCLUSION: These results suggest that high-dose irinotecan can be safely administered as first-line monotherapy to approximately two-thirds of patients who present with advanced CRC following a selective first cycle.

Full Text

Duke Authors

Cited Authors

  • Ychou, M; Raoul, JL; Desseigne, F; Borel, C; Caroli-Bosc, FX; Jacob, JH; Seitz, JF; Kramar, A; Hua, A; Lefebvre, P; Couteau, C; Merrouche, Y

Published Date

  • November 2002

Published In

Volume / Issue

  • 50 / 5

Start / End Page

  • 383 - 391

PubMed ID

  • 12439596

International Standard Serial Number (ISSN)

  • 0344-5704

Digital Object Identifier (DOI)

  • 10.1007/s00280-002-0506-7


  • eng

Conference Location

  • Germany