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.
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.
Authors: Kathryn Ottolino-Perry; Sergio A Acuna; Fernando A Angarita; Clara Sellers; Siham Zerhouni; Nan Tang; J Andrea McCart Journal: Mol Oncol Date: 2015-05-06 Impact factor: 6.603
Authors: Lisa M McGregor; Sheri L Spunt; Wayne L Furman; Clinton F Stewart; Paula Schaiquevich; Mark D Krailo; Roseanne Speights; Percy Ivy; Peter C Adamson; Susan M Blaney Journal: Cancer Date: 2009-04-15 Impact factor: 6.860
Authors: Smitha S Krishnamurthi; Joanna M Brell; Charles L Hoppel; Merrill J Egorin; Karen C Weaver; Xiaolin Li; Stephen T Ingalls; Eleanor G Zuhowski; Mark D Schluchter; Afshin Dowlati; Matthew M Cooney; Joseph Gibbons; Beth A Overmoyer; S Percy Ivy; Scot C Remick Journal: Cancer Chemother Pharmacol Date: 2008-04-15 Impact factor: 3.333
Authors: Paulo M Hoff; Everardo D Saad; Richard Pazdur; Robert Wolff; Yvonne Lassere; Karla R Bogaard; James L Abbruzzese Journal: Invest New Drugs Date: 2004-08 Impact factor: 3.850