PEPCOL: a GERCOR randomized phase II study of nanoliposomal irinotecan PEP02 (MM‐398) or irinotecan with leucovorin/5‐fluorouracil as second‐line therapy in metastatic colorectal cancer

• Published in: Cancer medicine (Malden, MA) Vol. 5; no. 4; pp. 676 - 683
• Main Authors: Chibaudel, Benoist, Maindrault‐Gœbel, Frédérique, Bachet, Jean‐Baptiste, Louvet, Christophe, Khalil, Ahmed, Dupuis, Olivier, Hammel, Pascal, Garcia, Marie‐Line, Bennamoun, Mostefa, Brusquant, David, Tournigand, Christophe, André, Thierry, Arbaud, Claire, Larsen, Annette K, Wang, Yi‐Wen, Yeh, C. Grace, Bonnetain, Franck, Gramont, Aimery
• Format: Journal Article
• Language: English
• Published: United States Wiley 01.04.2016; John Wiley and Sons Inc
• Subjects: Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols - adverse effects; Antineoplastic Combined Chemotherapy Protocols - therapeutic use; Camptothecin - administration & dosage; Camptothecin - analogs & derivatives; Cancer; Cancer Biology; Colorectal cancer; Colorectal Neoplasms - drug therapy; Colorectal Neoplasms - mortality; Colorectal Neoplasms - pathology; Combined Modality Therapy; Drug Combinations; Female; Fluorouracil - administration & dosage; Humans; Irinotecan; Leucovorin - administration & dosage; Life Sciences; Male; Medication; Middle Aged; MM398; nanoliposomal irinotecan; Neoplasm Metastasis; Original Research; PEP02; Pharmaceutical sciences; phase II; Quality of Life; Retreatment; Sucrose - administration & dosage; Sucrose - analogs & derivatives; Treatment Outcome; phase II; MM398; PEP02; Colorectal cancer; nanoliposomal irinotecan
• ISSN: 2045-7634; 2045-7634
• DOI: 10.1002/cam4.635

A multicenter, open‐label, noncomparative, randomized phase II study (PEPCOL) was conducted to evaluate the efficacy and safety of the irinotecan or PEP02 (MM‐398, nanoliposomal irinotecan) with leucovorin (LV)/5‐fluorouracil (5‐FU) combination as second‐line treatment in patients with metastatic colorectal cancer (mCRC). Patients with unresectable mCRC who had failed one prior oxaliplatin‐based first‐line therapy were randomized toirinotecan with LV/5‐FU (FOLFIRI) or PEP02 with LV/5‐FU (FUPEP; PEP02 80 mg/m2 with LV 400 mg/m2 on day 1 and 5‐FU 2400 mg/m2 on days 1–2). Bevacizumab (5 mg/kg, biweekly) was allowed in both arms. The primary endpoint was 2‐month response rate (RR). Fifty‐five patients were randomized (FOLFIRI, n = 27; FUPEP, n = 28). In the intent‐to‐treat population (n = 55), 2‐month RR response rate was observed in two (7.4%) and three (10.7%) patients in the FOLFIRI and FUPEP arms, respectively. The most common grade 3–4 adverse events reported in the respective FOLFIRI and FUPEP arms were diarrhea (33% vs. 21%), neutropenia (30% vs. 11%), mucositis (11% vs. 11%), and grade 2 alopecia (26% vs. 25%). FUPEP has activity and acceptable safety profile in oxaliplatin‐pretreated mCRC patients. MM‐398 (PEP02) is a novel, stable nanotherapeutic encapsulation of irinotecan. The PEPCOL study is the first randomized multicentre phase II study that was conducted to establish the efficacy and safety of the PEP02 or irinotecan with leucovorin/5‐fluorouracilcombination in the second‐line setting in patients with metastatic colorectal cancer failing prior oxaliplatin‐containing first‐line therapy. The main result of this study is that the FUPEP regimen exhibited promising tumor response and better safety profile as compared to standard FOLFIRI.