Mitomycin C and High‐Dose 5‐Fluorouracil With Folinic Acid as a Therapeutic Option for Heavily Pretreated Patients With Metastatic Colorectal Cancer: Prospective Phase II Trial

• Published in: The oncologist (Dayton, Ohio) Ohio), 2014-04, Vol.19 (4), p.356-357
• Main Authors: Stec, Rafał, Bodnar, Lubomir, Smoter, Marta, Korniluk, Jan, Kuchar, Agata, Młot, Beata, Szczylik, Cezary
• Format: Article
• Language: English
• Subjects: Aged; Antineoplastic Combined Chemotherapy Protocols - adverse effects; Antineoplastic Combined Chemotherapy Protocols - therapeutic use; Clinical Trial Results; Colorectal Neoplasms - drug therapy; Colorectal Neoplasms - mortality; Disease-Free Survival; Drug Administration Schedule; Fluorouracil - adverse effects; Fluorouracil - therapeutic use; Humans; Leucovorin - adverse effects; Leucovorin - therapeutic use; Middle Aged; Mitomycin - adverse effects; Mitomycin - therapeutic use; Neoplasm Metastasis - drug therapy; Prospective Studies; Treatment Outcome
• ISSN: 1083-7159; 1549-490X
• DOI: 10.1634/theoncologist.2014-0029

Background. Standard treatment for patients with unresectable colorectal cancer metastases includes chemotherapy regimens based on irinotecan, oxaliplatin, fluoropyrimidines, anti‐vascular endothelial growth factor therapy, and anti‐EGFR. Additional therapeutic options are needed for patients with good performance status who have disease progression during or after standard therapies. Methods. A nonrandomized phase II study was modeled as a two‐stage Chen design. Eligible patients had a diagnosis of metastatic colorectal cancer (mCRC) with progression after prior cytotoxic regimens based on oxaliplatin and irinotecan. Treatment consisted of mitomycin C in combination with high‐dose 5‐fluorouracil (5‐FU) and folinic acid (the MLF regimen; mitomycin C as an intravenous bolus of 6 mg/m2 i.v. on days 1 and 22 every 7 weeks; folinic acid at 250 mg/m2 in combination with 5‐FU at 2,600 mg/m2 as a continuous intravenous infusion (24 hours) weekly for 6 of every 7 weeks. Results. The median age of the 74 eligible patients was 62 years (range: 47–79 years). In these heavily pretreated patients with mCRC, the MLF regimen was the fourth or fifth line in more than 60% of the patients. Two patients (3.2%) achieved a partial response, and 33 (53.2%) achieved a best response of stable disease, defined as neither sufficient shrinkage to qualify for partial response nor sufficient increase to qualify for progressive disease. Median progression‐free survival was 4.9 months. The median overall survival was 9.7 months. The most common nonhematologic side effects included mucositis (24.4% for all grades, and 9.5% with grade 3/4), diarrhea (15.0% for all grades, 13.6% with grade 3/4), fatigue (44.7% for all grades, 13.6% with grade 3/4), nausea (12.3% for all grades, 6.8% with grade 3/4), and peripheral neuropathy (17.6% for all grades, 2.7% with grade 3/4). Among the most frequent hematological toxicities were neutropenia (27.1% for all grades, 14.9% with grade 3/4), thrombocytopenia (18.9% for all grades, 8.1% with grade 3/4), and anemia (13.6% for all grades, 4.1% with grade 3/4). Dose reductions due to adverse events were necessary in 29 of 74 patients (37.6%), and discontinuation of therapy due to toxicity was necessary for 14 of 74 patients (18.2%). Conclusion. Our study shows the MLF regimen can be administered safely to patients with heavily pretreated mCRC. Median progression‐free and overall survival compares favorably with other options used or approved in this settin