Second-Line Treatment of Advanced Colorectal Cancer with a Biweekly Oxaliplatin plus Irinotecan Combination Regimen

Onkologie. 2002 Aug;25(4):358-62. doi: 10.1159/000066054.

Abstract

Background: Both oxaliplatin and irinotecan have demonstrated antitumor activity in pretreated colorectal cancer; experimental and early clinical data suggest that these two drugs may act synergistically. The aim of this study was to document the therapeutic index of a biweekly combination regimen in patients with metastatic colorectal cancer failing prior palliative first-line chemotherapy with raltitrexed.

Patients and methods: In this study 27 patients with metastatic colorectal cancer were analyzed, who progressed while on or within 6 months after discontinuation of palliative first-line chemotherapy with raltitrexed. They received oxaliplatin 85 mg/m(2) and irinotecan 150 mg/m(2) both given on days 1 and 15 every 4 weeks.

Results: The confirmed overall response rate was 37% (95% confidence interval, 19.4-57.7%), including 2 complete and 8 partial remissions. 12 additional patients (44.4%) had stable disease, and in only 5 cases (18.5%) disease progression was not influenced by chemotherapy. The median progression-free survival for all 27 patients was 8 months (range, 1-16+ months), and 16 patients (59%) are still alive after a median follow-up time of 12.5 months. Hematologic adverse reactions, specifically leukocytopenia and neutropenia, were common though generally mild to moderate with grade 4 toxicity occurring in only 2 cases. The most frequent non-hematologic adverse events included gastrointestinal symptoms; severe nausea/emesis and diarrhea, however, were noted in only 2 and 3 patients, respectively.

Conclusions: Our data suggest that the described biweekly combination regimen of oxaliplatin and irinotecan has substantial antitumor activity in patients with progressive, raltitrexed-pretreated metastatic colorectal cancer. Because of its favorable toxicity profile, further evaluation of this combination seems warranted.

MeSH terms

  • Adult
  • Aged
  • Antineoplastic Combined Chemotherapy Protocols / adverse effects
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Camptothecin / administration & dosage*
  • Camptothecin / adverse effects
  • Camptothecin / analogs & derivatives*
  • Colorectal Neoplasms / drug therapy*
  • Colorectal Neoplasms / mortality
  • Colorectal Neoplasms / pathology
  • Disease Progression
  • Disease-Free Survival
  • Dose-Response Relationship, Drug
  • Drug Administration Schedule
  • Female
  • Follow-Up Studies
  • Humans
  • Irinotecan
  • Male
  • Middle Aged
  • Neoplasm Staging
  • Organoplatinum Compounds / administration & dosage*
  • Organoplatinum Compounds / adverse effects
  • Oxaliplatin
  • Palliative Care
  • Quinazolines / administration & dosage
  • Quinazolines / adverse effects
  • Thiophenes / administration & dosage
  • Thiophenes / adverse effects
  • Treatment Failure

Substances

  • Organoplatinum Compounds
  • Quinazolines
  • Thiophenes
  • Oxaliplatin
  • Irinotecan
  • raltitrexed
  • Camptothecin