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/m2. Once a dose of 60 mg/m2 was attained, the weekly dose of irinotecan was escalated, from 40 mg/m2 to 85 mg/m2. 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/m2 and irinotecan 50 mg/m2, weekly × 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.
Original language | English (US) |
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Pages (from-to) | 1490-1496 |
Number of pages | 7 |
Journal | Annals of Oncology |
Volume | 13 |
Issue number | 9 |
DOIs | |
State | Published - Sep 2002 |
Keywords
- Colorectal cancer
- Irinotecan
- Oxaliplatin
ASJC Scopus subject areas
- Hematology
- Oncology