Phase I study of weekly oxaliplatin plus irinotecan in previously treated patients with metastatic colorectal cancer Journal Article

Authors: Kemeny, N.; Tong, W.; Gonen, M.; Stockman, J.; Di Lauro, C.; Teitcher, J.; White, P.; Price, C.; Saltz, L.; Sharma, S.; Graham, M.
Article Title: Phase I study of weekly oxaliplatin plus irinotecan in previously treated patients with metastatic colorectal cancer
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.
Keywords: adult; clinical article; controlled study; treatment outcome; aged; aged, 80 and over; middle aged; survival analysis; clinical trial; drug tolerability; salvage therapy; area under the curve; diarrhea; dose response; side effect; pyridines; cancer patient; neoplasm staging; colorectal cancer; metastasis; controlled clinical trial; leukopenia; antineoplastic combined chemotherapy protocols; drug administration schedule; camptothecin; antineoplastic activity; dose-response relationship, drug; risk assessment; irinotecan; colorectal neoplasms; dna; drug distribution; probability; drug response; neoplasm metastasis; drug clearance; dna adduct; loperamide; phase 1 clinical trial; drug half life; oxaliplatin; organoplatinum compounds; neurologic disease; abdominal cramp; atropine; sweating; salivation; humans; prognosis; human; male; female; priority journal; article; oxal
Journal Title: Annals of Oncology
Volume: 13
Issue: 9
ISSN: 0923-7534
Publisher: Oxford University Press  
Date Published: 2002-09-01
Start Page: 1490
End Page: 1496
Language: English
DOI: 10.1093/annonc/mdf247
PUBMED: 12196376
PROVIDER: scopus
Notes: Export Date: 14 November 2014 -- Source: Scopus
Citation Impact
MSK Authors
  1. William Ping-Yiu Tong
    158 Tong
  2. Leonard B Saltz
    738 Saltz
  3. Mithat Gonen
    915 Gonen
  4. Sunil Sharma
    26 Sharma
  5. Nancy Kemeny
    514 Kemeny
  6. Christin Nirvana Price
    1 Price
  7. Margaret   Graham
    1 Graham
  8. Pascale Marthe White
    2 White