Randomized Phase II Study of Irinotecan Plus Mitomycin C vs. Oxaliplatin Plus Mitomycin C in Patients with Advanced Fluoropyrimidine Leucovorin-Pretreated Colorectal Cancer

• Published in: Cancer investigation Vol. 20; no. 1; pp. 60 - 68
• Main Authors: Scheithauer, Werner, Kornek, Gabriela V., Brugger, Stefan, Ullrich-Pur, Herbert, Valencak, Julia, Raderer, Markus, Fiebiger, Wolfgang, Kovats, Erwin, Lang, Fritz, Depisch, Dieter
• Format: Journal Article
• Language: English
• Published: New York, NY Informa UK Ltd 2002; Taylor & Francis; Informa Healthcare
• Subjects: Adenocarcinoma - drug therapy; Adenocarcinoma - secondary; Adult; Advanced colorectal cancer; Aged; Antineoplastic agents; Antineoplastic Combined Chemotherapy Protocols - therapeutic use; Biological and medical sciences; Camptothecin - administration & dosage; Camptothecin - analogs & derivatives; Chemotherapy; Colorectal Neoplasms - drug therapy; Colorectal Neoplasms - pathology; Disease Progression; Disease-Free Survival; Female; Humans; Irinotecan; Leucovorin - administration & dosage; Male; Medical sciences; Middle Aged; Mitomycin - administration & dosage; Mitomycin C; Neoplasm Metastasis; Neoplasm Staging; Organoplatinum Compounds - administration & dosage; Oxaliplatin; Pharmacology. Drug treatments; Prospective Studies; Salvage Therapy; Second-line treatment; Treatment Outcome; Adenocarcinoma; Antineoplastic agent; Rectal disease; Intravenous administration; Toxicity; Calcium folinate; Randomization; Oxaliplatin; Phase II trial; Intestinal disease; Advanced stage; Colon; Pretreatment; Platinum II Complexes; Human; Drug combination; Mitomycin; Treatment efficiency; Fluoropyrimidine derivatives; Malignant tumor; Colonic disease; Irinotecan; Chemotherapy; Treatment; Rectum; Digestive diseases; Pyrimidine derivatives; Comparative study
• ISSN: 0735-7907; 1532-4192
• DOI: 10.1081/CNV-120000367

Introduction: Irinotecan and oxaliplatin are two new agents with promising activity in advanced colorectal cancer. Based on preclinical and clinical evidence that both drugs might act synergistically with mitomycin C, a randomized study using a 'pick the winner' design was undertaken to determine the effectiveness and tolerance of these two combination schedules in patients with fluoropyrimidine leucovorin-pretreated advanced colorectal cancer. Patients and Methods: Sixty-four patients with metastatic colorectal cancer, who progressed while receiving or within 6 months after discontinuing palliative chemotherapy with fluoropyrimidines leucovorin were enrolled onto this study. They were randomly assigned to treatment with irinotecan 120 mg m2 on days 1+15 plus mitomycin C 8 mg m2 on day 1 (arm A) or oxaliplatin 85 mg m2 on days 1+15 plus mitomycin C 8 mg m2 on day 1 (arm B). In both treatment arms, courses were repeated every 4 weeks. Results: The objective response rate in arm A is 7 33 (21.2%; 95% confidence interval, 9.0-38.9%) as compared to 5 31 in arm B (16.1%; 95% CI, 5.5-34.7%). Stable disease was noted in 48.5 vs. 45.2%, whereas the tumor progressed in 30.3 vs. 38.7%, respectively. Similar to the recorded response activities, the difference of the two combination regimens in terms of median time to progression (7.0 vs. 5.2 months) and overall survival (12.0 vs. 11.2 months) was only minor and clincally insignificant. The tolerance of treatment was acceptable in both arms, though severe adverse reactions requiring dose reductions (30 vs.16%) and treatment delays (22 vs. 13% of courses) were more commonly noted with irinotecan mitomycin C. The most common toxicities in arm A were neutropenia (85%; WHO grade 3 4 in 33%), thrombocytopenia (52%), diarrhea (45%), emesis (52%) and alopecia (92%). In arm B, common toxicities included neutropenia (68%; grade 3 4 in 13%), thrombocytopenia (81%), emesis (52%), and peripheral neutropathy (48%). Conclusions: Both mitomycin C combination regimens seem to provide an acceptable therapeutic index in patients with fluoropyrimidine leucovorin-pretreated metastatic colorectal cancer. In view of the increasing need for a broader chemotherapeutic armentarium for second-line therapy of this common malignant disease, both regimens may be worthwhile to undergo further clinical investigation.