title: Excess toxicity associated with docetaxel and irinotecan in patients with metastatic, gemcitabine-refractory pancreatic cancer: results of a phase II study.
abstract: BACKGROUND
  No therapeutic standard of care exists for patients with advanced pancreatic cancer who progress following first-line treatment with a gemcitabine-based regimen. There is evidence of synergistic activity between docetaxel and irinotecan, and the combination of these two agents has shown promising efficacy in the first-line setting for advanced pancreatic cancer. We, therefore, evaluated this regimen in patients with gemcitabine-refractory disease.
  
  
  METHODS
  Eligible patients with metastatic pancreatic adenocarcinoma were required to have an elevated serum CA19-9 (> 2x ULN) and exposure to one or two prior chemotherapy regimens, including one gemcitabine-based. Treatment consisted of docetaxel 65 mg/m2 and irinotecan 160 mg/m2, both administered every 21 days. Serum CA19-9 levels were measured at the start of each treatment cycle and CT scans performed after every two cycles.
  
  
  RESULTS
  Fourteen patients were enrolled before the study was closed due to excess toxicity. The most common grade 3/4 toxicities included neutropenia/leukopenia, nausea and vomiting, and diarrhea. Fully half of patients received only 1 treatment cycle, with a median time to treatment failure of 36 days. No objective responses were observed, although 3 patients had stable disease for at least 6 cycles. Overall survival for the entire cohort was 134 days, with a 6-month survival rate of 36%.
  
  
  CONCLUSIONS
  The combination of docetaxel and irinotecan given on a 21-day cycle is associated with excess toxicity in gemcitabine-refractory patients with advanced pancreatic cancer. Although select patients may benefit from treatment, the overall risk:benefit ratio is unfavorable, and other dosing regimens and therapeutic options should be explored in this setting.
authors.affiliation: University of California at San Francisco Comprehensive Cancer Center, San Francisco, California 94115, USA. andrewko@medicine.ucsf.edu
authors.forename: Andrew H
authors.initials: AH
authors.lastname: Ko
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Dito
authors.forename: Brian
authors.initials: B
authors.lastname: Schillinger
authors.forename: Alan P
authors.initials: AP
authors.lastname: Venook
authors.forename: Emily K
authors.initials: EK
authors.lastname: Bergsland
authors.forename: Margaret A
authors.initials: MA
authors.lastname: Tempero
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy* / Q000401:mortality / Q000556:secondary*; D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000633:toxicity*; D002166:Camptothecin / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000633:toxicity; D003841:Deoxycytidine / Q000031:analogs & derivatives / Q000627:therapeutic use; D000077143:Docetaxel; D019008:Drug Resistance, Neoplasm; D005260:Female; D006801:Humans; D000077146:Irinotecan; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D010190:Pancreatic Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology*; D043823:Taxoids / Q000008:administration & dosage / Q000633:toxicity; D000093542:Gemcitabine
chemical_list: D043823:Taxoids; D003841:Deoxycytidine; D000077143:Docetaxel; D000077146:Irinotecan; D002166:Camptothecin; D000093542:Gemcitabine