Phase I study of weekly oxaliplatin plus irinotecan in previously treated patients with metastatic colorectal cancer. Academic Article uri icon

Overview

abstract

  • BACKGROUND: In vitro synergy between Oxal (oxaliplatin) and CPT-11 (irinotecan) has been reported. Oxaliplatin exerts its antineoplastic activity through the formation of platinum-DNA adducts. Resistance to oxaliplatin is through repair of these adducts, which is inhibited by irinotecan. PATIENTS AND METHODS: Oxaliplatin and irinotecan were administered weekly for 4 weeks followed by a 2-week rest period. The dose of oxaliplatin was escalated first, starting at 30 mg/m(2). Once a dose of 60 mg/m(2) was attained, the weekly dose of irinotecan was escalated, from 40 mg/m(2) to 85 mg/m(2). A total of 49 previously treated patients with metastatic colorectal cancer were entered in order to establish the maximum tolerated dose. Pharmacokinetics of oxaliplatin and irinotecan were analyzed. RESULTS: Forty-nine patients were evaluable for toxicity. The recommended phase II doses for this combination are oxaliplatin 60 mg/m(2) and irinotecan 50 mg/m(2), weekly x 4 q 6 weeks. Diarrhea was the most common dose-limiting toxicity. No pharmacological interactions were noted between oxaliplatin and irinotecan. Twelve of the 47 evaluable patients (26%) achieved a partial response. CONCLUSION: Weekly combination of oxaliplatin and irinotecan appears to be a well tolerated and active regimen in patients previously treated for metastatic colorectal cancer. Further investigations of this regimen are warranted.

publication date

  • September 1, 2002

Research

keywords

  • Antineoplastic Combined Chemotherapy Protocols
  • Camptothecin
  • Colorectal Neoplasms
  • Organoplatinum Compounds
  • Pyridines
  • Salvage Therapy

Identity

Scopus Document Identifier

  • 0036740374

Digital Object Identifier (DOI)

  • 10.1093/annonc/mdf247

PubMed ID

  • 12196376

Additional Document Info

volume

  • 13

issue

  • 9