title: A phase II study of fixed-dose rate gemcitabine plus low-dose cisplatin followed by consolidative chemoradiation for locally advanced pancreatic cancer.
abstract: OBJECTIVE
  The optimal strategy for treating locally advanced pancreatic cancer remains controversial, including the respective roles and timing of chemotherapy and radiation. We conducted a Phase II nonrandomized trial to evaluate sequential chemotherapy followed by chemoradiation in this patient population.
  
  
  METHODS
  Chemotherapy naive patients with locally advanced pancreatic adenocarcinoma were treated with fixed-dose rate gemcitabine (1,000 mg/m(2) at 10 mg/m(2)/min) plus cisplatin 20 mg/m(2) on Days 1 and 15 of a 28-day cycle. Those without evidence of extrapancreatic metastases after six cycles of chemotherapy received radiation (5,040 cGy over 28 fractions) with concurrent capecitabine (800 mg/m(2) orally twice daily on the day of radiation) as a radiosensitizer.
  
  
  RESULTS
  A total of 25 patients were enrolled with a median follow-up time of 656 days. Twelve patients (48%) successfully received all six cycles of chemotherapy plus chemoradiation. Eight patients (32%) progressed during chemotherapy, including 7 with extrapancreatic metastases. Grade 3/4 hematologic toxicities were uncommon. Two patients sustained myocardial infarctions during chemotherapy, and 4 were hospitalized for infectious complications, although none in the setting of neutropenia. Median time to progression was 10.5 months and median survival was 13.5 months, with an estimated 1-year survival rate of 62%. Patients receiving all components of therapy had a median survival of 17.0 months.
  
  
  CONCLUSIONS
  A strategy of initial fixed-dose rate gemcitabine-based chemotherapy, followed by chemoradiation, shows promising efficacy for treatment of locally advanced disease. A substantial proportion of patients will be identified early on as having extrapancreatic disease and spared the potential toxicities associated with radiation.
authors.affiliation: Division of Hematology/Oncology, University of California at San Francisco, San Francisco, CA 94115, USA. andrewko@medicine.ucsf.edu
authors.forename: Andrew H
authors.initials: AH
authors.lastname: Ko
authors.forename: Jeanne M
authors.initials: JM
authors.lastname: Quivey
authors.forename: Alan P
authors.initials: AP
authors.lastname: Venook
authors.forename: Emily K
authors.initials: EK
authors.lastname: Bergsland
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Dito
authors.forename: Brian
authors.initials: B
authors.lastname: Schillinger
authors.forename: Margaret A
authors.initials: MA
authors.lastname: Tempero
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000964:Antimetabolites, Antineoplastic / Q000008:administration & dosage; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage*; D002140:California / Q000453:epidemiology; D002945:Cisplatin / Q000008:administration & dosage; D015897:Comorbidity; D003841:Deoxycytidine / Q000008:administration & dosage / Q000031:analogs & derivatives; D004305:Dose-Response Relationship, Drug; D005260:Female; D005767:Gastrointestinal Diseases / Q000453:epidemiology; D006801:Humans; D015994:Incidence; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000401:mortality* / Q000517:prevention & control; D010190:Pancreatic Neoplasms / Q000401:mortality* / Q000601:surgery / Q000628:therapy*; D011379:Prognosis; D011832:Radiation Injuries / Q000453:epidemiology*; D011838:Radiation-Sensitizing Agents / Q000008:administration & dosage; D018714:Radiotherapy, Adjuvant / Q000401:mortality*; D018570:Risk Assessment / Q000379:methods; D012307:Risk Factors; D016019:Survival Analysis; D015996:Survival Rate; D016896:Treatment Outcome; D000093542:Gemcitabine
chemical_list: D000964:Antimetabolites, Antineoplastic; D011838:Radiation-Sensitizing Agents; D003841:Deoxycytidine; D002945:Cisplatin; D000093542:Gemcitabine