title: A randomized phase II study of PEP02 (MM-398), irinotecan or docetaxel as a second-line therapy in patients with locally advanced or metastatic gastric or gastro-oesophageal junction adenocarcinoma.
abstract: BACKGROUND
  PEP02 is a novel highly stable liposomal nanocarrier formulation of irinotecan. This randomized phase II study evaluated the efficacy and safety of single agent PEP02 compared with irinotecan or docetaxel in the second-line treatment of advanced oesophago-gastric (OG) cancer.
  
  
  METHODS
  Patients with locally advanced/metastatic disease who had failed one prior chemotherapy regimen were randomly assigned to PEP02 120 mg/m(2), irinotecan 300 mg/m(2) or docetaxel (Taxotere) 75 mg/m(2) every 3 weeks. The primary end point was objective response rate (ORR). Simon's two-stage design was used and the ORR of interest was 20% (α = 0.05, type II error β = 0.10, null hypothesis of ORR was 5%).
  
  
  RESULTS
  Forty-four patients per arm received treatment, and 124 were assessable for response. The ORR statistical threshold for the first stage was reached in all arms. In the intent-to-treat (ITT) population, ORRs were 13.6% (6/44), 6.8% (3/44) and 15.9% (7/44) in the PEP02, irinotecan and docetaxel arms, respectively. The median progression-free survival (PFS) and overall survival were similar between the trial arms. Commonest grade 3-4 adverse event reported was diarrhoea in the PEP02 and irinotecan groups (27.3% versus 18.2%).
  
  
  CONCLUSIONS
  The ORR associated with PEP02 was comparable with docetaxel and numerically greater than that of irinotecan. PEP02 warrants further evaluation in the advanced gastric cancer setting.
authors: Department of Medicine, The Royal Marsden Hospital, Sutton, UK.
authors: A C
authors: AC
authors: Roy
authors: S R
authors: SR
authors: Park
authors: D
authors: D
authors: Cunningham
authors: Y K
authors: YK
authors: Kang
authors: Y
authors: Y
authors: Chao
authors: L T
authors: LT
authors: Chen
authors: C
authors: C
authors: Rees
authors: H Y
authors: HY
authors: Lim
authors: J
authors: J
authors: Tabernero
authors: F J
authors: FJ
authors: Ramos
authors: M
authors: M
authors: Kujundzic
authors: M B
authors: MB
authors: Cardic
authors: C G
authors: CG
authors: Yeh
authors: A
authors: A
authors: de Gramont
mesh_terms: D000230:Adenocarcinoma / Q000175:diagnosis / Q000188:drug therapy* / Q000401:mortality; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002166:Camptothecin / Q000008:administration & dosage / Q000031:analogs & derivatives*; D000077143:Docetaxel; D004337:Drug Carriers / Q000008:administration & dosage*; D004938:Esophageal Neoplasms / Q000175:diagnosis / Q000188:drug therapy* / Q000401:mortality; D004943:Esophagogastric Junction / Q000187:drug effects / Q000473:pathology*; D005260:Female; D006801:Humans; D000077146:Irinotecan; D008297:Male; D008875:Middle Aged; D053769:Nanocapsules / Q000008:administration & dosage; D013274:Stomach Neoplasms / Q000175:diagnosis / Q000188:drug therapy* / Q000401:mortality; D015996:Survival Rate / Q000639:trends; D043823:Taxoids / Q000008:administration & dosage*
chemical_list: D004337:Drug Carriers; D053769:Nanocapsules; D043823:Taxoids; D000077143:Docetaxel; D000077146:Irinotecan; D002166:Camptothecin
keywords: docetaxel; irinotecan; liposomal irinotecan; oesophago-gastric cancer; phase II; second line