title: Randomized phase III study of exatecan and gemcitabine compared with gemcitabine alone in untreated advanced pancreatic cancer.
abstract: OBJECTIVE
  Exatecan mesylate is a hexacyclic, water-soluble, topoisomerase-1 inhibitor. Exatecan has single-agent and combination activity with gemcitabine in advanced pancreatic cancer. A multicenter, randomized, phase III trial comparing exatecan plus gemcitabine versus gemcitabine alone in advanced pancreatic cancer was conducted.
  
  
  METHODS
  Eligibility criteria included Karnofsky performance status > or = 60%, locally advanced or metastatic pancreatic adenocarcinoma, and no prior chemotherapy. Radiation alone for locally advanced disease was permitted. Patients were randomly assigned on a 1:1 basis. For the exatecan plus gemcitabine arm, exatecan 2.0 mg/m2 and gemcitabine 1,000 mg/m2 were administered on days 1 and 8, every 3 weeks. Gemcitabine alone was dosed at 1,000 mg/m2 up to 7 weeks in the first cycle, then once a week for the first 3 weeks of a 4-week cycle. Tumor assessment was performed every 6 weeks. The primary end point was overall survival. An intent-to-treat analysis was used.
  
  
  RESULTS
  From August 2001 to January 2003, 349 patients were randomly assigned, 175 to exatecan plus gemcitabine and 174 to gemcitabine alone. Twenty-four patients (6.9%) were not treated. The median survival time was 6.7 months for exatecan plus gemcitabine and 6.2 months for gemcitabine alone (P = .52). One complete response (CR; < 1%) and 11 partial responses (PRs; 6.3%) were observed in the exatecan plus gemcitabine treatment group, and one CR (< 1%) and eight PRs (4.6%) were observed in the gemcitabine-alone group. Grade 3 and 4 toxicities were higher for the exatecan plus gemcitabine arm versus the gemcitabine alone arm; neutropenia (30% v 15%) and thrombocytopenia (15% v 4%).
  
  
  CONCLUSIONS
  Exatecan plus gemcitabine was not superior to gemcitabine alone with respect to overall survival in the first-line treatment of advanced pancreatic cancer.
authors.affiliation: Memorial Sloan-Kettering Cancer Center, New York, NY 10022, USA. abou-alg@mskcc.org
authors.forename: Ghassan K
authors.initials: GK
authors.lastname: Abou-Alfa
authors.forename: Richard
authors.initials: R
authors.lastname: Letourneau
authors.forename: Graydon
authors.initials: G
authors.lastname: Harker
authors.forename: Manuel
authors.initials: M
authors.lastname: Modiano
authors.forename: Herbert
authors.initials: H
authors.lastname: Hurwitz
authors.forename: Nerses Simon
authors.initials: NS
authors.lastname: Tchekmedyian
authors.forename: Kevie
authors.initials: K
authors.lastname: Feit
authors.forename: Judie
authors.initials: J
authors.lastname: Ackerman
authors.forename: Robert L
authors.initials: RL
authors.lastname: De Jager
authors.forename: S Gail
authors.initials: SG
authors.lastname: Eckhardt
authors.forename: Eileen M
authors.initials: EM
authors.lastname: O'Reilly
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000964:Antimetabolites, Antineoplastic / Q000008:administration & dosage / Q000627:therapeutic use*; D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D002166:Camptothecin / Q000008:administration & dosage / Q000031:analogs & derivatives*; D003841:Deoxycytidine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000627:therapeutic use; D018572:Disease-Free Survival; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D010190:Pancreatic Neoplasms / Q000188:drug therapy* / Q000473:pathology; D016019:Survival Analysis; D016896:Treatment Outcome; D000093542:Gemcitabine
chemical_list: D000964:Antimetabolites, Antineoplastic; D000972:Antineoplastic Agents, Phytogenic; D003841:Deoxycytidine; C095887:exatecan; D002166:Camptothecin; D000093542:Gemcitabine