title: 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.
abstract: 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/m(2) with LV 400 mg/m(2) on day 1 and 5-FU 2400 mg/m(2) 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.
authors.affiliation: Department of Medical Oncology, Franco-British Institute, Levallois-Perret, France.|Groupe Coopérateur Multidisciplinaire en Oncologie (GERCOR), Paris, France.|Preclinical and Translational Cancer Research Unit, AAREC Filia Research (AFR), Paris, France.
authors.forename: Benoist
authors.initials: B
authors.lastname: Chibaudel
authors.affiliation: Department of Medical Oncology, Saint-Antoine Hospital, Assistance Publique des Hôpitaux de Paris (APHP), Paris, France.
authors.forename: Frédérique
authors.initials: F
authors.lastname: Maindrault-Gœbel
authors.affiliation: Department of Gastroenterology, La Pitié-Salpetrière Hospital, Assistance Publique des Hôpitaux de Paris (APHP), Paris, France.
authors.forename: Jean-Baptiste
authors.initials: JB
authors.lastname: Bachet
authors.affiliation: Department of Medical Oncology, Montsouris Mutualiste Institute, Paris, France.
authors.forename: Christophe
authors.initials: C
authors.lastname: Louvet
authors.affiliation: Department of Medical Oncology, Tenon Hospital, Assistance Publique des Hôpitaux de Paris (APHP), Paris, France.
authors.forename: Ahmed
authors.initials: A
authors.lastname: Khalil
authors.affiliation: Department of Medical Oncology, Victor Hugo Clinic, Le Mans, France.
authors.forename: Olivier
authors.initials: O
authors.lastname: Dupuis
authors.affiliation: Department of Gastroenterology, Beaujon Hospital, Assistance Publique des Hôpitaux de Paris (APHP), Clichy, France.
authors.forename: Pascal
authors.initials: P
authors.lastname: Hammel
authors.affiliation: Department of Medical Oncology, Saint-Antoine Hospital, Assistance Publique des Hôpitaux de Paris (APHP), Paris, France.
authors.forename: Marie-Line
authors.initials: ML
authors.lastname: Garcia
authors.affiliation: Department of Medical Oncology, Montsouris Mutualiste Institute, Paris, France.
authors.forename: Mostefa
authors.initials: M
authors.lastname: Bennamoun
authors.affiliation: Groupe Coopérateur Multidisciplinaire en Oncologie (GERCOR), Paris, France.
authors.forename: David
authors.initials: D
authors.lastname: Brusquant
authors.affiliation: Department of Medical Oncology, Henri Mondor Hospital, Créteil, France.
authors.forename: Christophe
authors.initials: C
authors.lastname: Tournigand
authors.affiliation: Department of Medical Oncology, Saint-Antoine Hospital, Assistance Publique des Hôpitaux de Paris (APHP), Paris, France.
authors.forename: Thierry
authors.initials: T
authors.lastname: André
authors.affiliation: Methodological and quality of life unit in oncology (EA3181) & Quality of life and cancer clinical research platform, CHU Besançon, Besançon, France.
authors.forename: Claire
authors.initials: C
authors.lastname: Arbaud
authors.affiliation: Cancer Biology and Therapeutics, INSERM U938 and Pierre and Marie Curie University, Paris, France.
authors.forename: Annette K
authors.initials: AK
authors.lastname: Larsen
authors.affiliation: PharmaEngine, Inc., Taipei, Taiwan.
authors.forename: Yi-Wen
authors.initials: YW
authors.lastname: Wang
authors.affiliation: PharmaEngine, Inc., Taipei, Taiwan.
authors.forename: C Grace
authors.initials: CG
authors.lastname: Yeh
authors.affiliation: Methodological and quality of life unit in oncology (EA3181) & Quality of life and cancer clinical research platform, CHU Besançon, Besançon, France.
authors.forename: Franck
authors.initials: F
authors.lastname: Bonnetain
authors.affiliation: Department of Medical Oncology, Franco-British Institute, Levallois-Perret, France.
authors.forename: Aimery
authors.initials: A
authors.lastname: de Gramont
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D002166:Camptothecin / Q000008:administration & dosage / Q000031:analogs & derivatives; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology*; D003131:Combined Modality Therapy; D004338:Drug Combinations; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage; D006801:Humans; D000077146:Irinotecan; D002955:Leucovorin / Q000008:administration & dosage; D008297:Male; D008875:Middle Aged; D009362:Neoplasm Metastasis; D011788:Quality of Life; D019233:Retreatment; D013395:Sucrose / Q000008:administration & dosage / Q000031:analogs & derivatives; D016896:Treatment Outcome
chemical_list: D004338:Drug Combinations; D013395:Sucrose; D000077146:Irinotecan; C584112:irinotecan sucrosofate; D002955:Leucovorin; D005472:Fluorouracil; D002166:Camptothecin
keywords: Colorectal cancer; MM398; PEP02; nanoliposomal irinotecan; phase II