Skip to main content

Advertisement

Log in

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

  • Original Article
  • Published:
Cancer Chemotherapy and Pharmacology Aims and scope Submit manuscript

Abstract

Purpose. The efficacy and safety of single-agent, high-dose irinotecan (CPT-11, Campto) 500 mg/m2 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/m2 every 3 weeks, which could be escalated to 500 mg/m2 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/m2).

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/m2 (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/m2.

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.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

Author information

Authors and Affiliations

Authors

Additional information

Electronic Publication

Rights and permissions

Reprints and permissions

About this article

Cite this article

Ychou, .M., Raoul, .J., Desseigne, .F. et al. High-dose, single-agent irinotecan as first-line therapy in the treatment of metastatic colorectal cancer. Cancer Chemother Pharmacol 50, 383–391 (2002). https://doi.org/10.1007/s00280-002-0506-7

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00280-002-0506-7

Navigation