title: Phase II trial of oral rubitecan in previously treated pancreatic cancer patients.
abstract: BACKGROUND
  Additional systemic treatments for locally advanced or metastatic pancreatic cancer are needed, as current treatment options produce only modest survival benefits. Rubitecan (Orathecin; Supergen Inc., Dublin, CA, http://www.supergen.com) is an orally active camptothecin derivative with demonstrated responses in patients with pancreatic cancer in early clinical trials. This phase II, open-label trial was developed to assess the safety and efficacy of rubitecan in patients with locally advanced or metastatic pancreatic cancer refractory to conventional chemotherapy.
  
  
  METHODS
  Fifty-eight patients with failed or relapsed advanced pancreatic cancer after receiving at least one prior chemotherapy regimen were enrolled to receive eight consecutive weeks of treatment with rubitecan at a dose of 1.5 mg/m2 orally on five consecutive days per week, followed by 2 days off therapy, repeatedly. The primary end point was response rate. Time to progression, overall survival, changes in CA19-9 levels, and the composite measure of clinical benefit response were evaluated as secondary end points.
  
  
  RESULTS
  Among 43 patients with measurable disease, 7% (3/43) achieved partial responses and 16% (7/43) had disease stabilization for an overall response and disease stabilization rate of 23%. All responses were confirmed by independent radiology review. Median survival was longer in responding patients than in the overall study cohort (10 months versus 3 months). Gastrointestinal and hematologic toxicities were the most commonly reported adverse events.
  
  
  CONCLUSIONS
  Oral rubitecan produced responses and was well tolerated by heavily pretreated patients with refractory pancreatic cancer. The overall risk-benefit profile of oral rubitecan appears promising, supporting further evaluation in phase III trials in patients with refractory and chemotherapy-naive pancreatic cancer.
authors.affiliation: III, The Sarah Cannon Cancer Center, 250 25th Avenue North, Suite 110, Nashville, Tennessee 37203, USA. hburris@tnonc.com
authors.forename: Howard A
authors.initials: HA
authors.lastname: Burris
authors.forename: Saul
authors.initials: S
authors.lastname: Rivkin
authors.forename: Robert
authors.initials: R
authors.lastname: Reynolds
authors.forename: Jules
authors.initials: J
authors.lastname: Harris
authors.forename: Arnold
authors.initials: A
authors.lastname: Wax
authors.forename: Hal
authors.initials: H
authors.lastname: Gerstein
authors.forename: Karl L
authors.initials: KL
authors.lastname: Mettinger
authors.forename: Arthur
authors.initials: A
authors.lastname: Staddon
mesh_terms: D000284:Administration, Oral; D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D002166:Camptothecin / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use*; D018450:Disease Progression; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D010190:Pancreatic Neoplasms / Q000188:drug therapy* / Q000473:pathology; D016019:Survival Analysis
chemical_list: D000970:Antineoplastic Agents; C079905:rubitecan; D002166:Camptothecin