title: Phase I study of weekly gemcitabine as a radiation sensitizer for unresectable pancreatic cancer.
abstract: OBJECTIVE
  To determine the maximal tolerated dose and dose-limiting toxicities (DLTs) of weekly gemcitabine with concurrent radiotherapy (RT) in patients with unresectable adenocarcinoma of the pancreas.
  
  
  METHODS
  Patients who had locally advanced or recurrent unresectable pancreatic cancer were eligible. Gemcitabine was administered as a 30-min infusion once weekly for a total of five cycles during the course of RT. The starting dose of gemcitabine was 350 mg/m(2)/wk. Doses were escalated by increments of 25% in successive cohorts of 3-6 patients. RT was delivered at 180 cGy/d to a total dose of 5400-5580 cGy to the gross tumor volume.
  
  
  RESULTS
  Nineteen patients were entered in this study through three dose levels (350-550 mg/m(2)/wk). The maximal tolerated dose was determined to be 440 mg/m(2)/wk. The DLTs were neutropenia, thrombocytopenia, and failure to receive all five cycles of gemcitabine. Other non-DLTs included 16 Grade III toxicities, which consisted of thrombosis, infection, nausea, vomiting, hypotension, constipation, diarrhea, and fatigue. One patient at each gemcitabine dose level experienced Grade IV vomiting, and the patient at the 550 mg/m(2) dose developed Grade IV anorexia.
  
  
  CONCLUSIONS
  The maximal tolerated dose of gemcitabine when administered as a 30-min infusion once weekly during RT for unresectable pancreatic cancer was found to be 440 mg/m(2)/wk. The DLTs were neutropenia, thrombocytopenia, and failure to receive all five cycles of chemotherapy. Concurrent gemcitabine and RT is reasonably well tolerated and deserves additional evaluation against the current standard of care.
authors.affiliation: Radiation Oncology Sciences Program, Division of Cancer Treatment, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA. mpoggi@usuhs.mil
authors.forename: Matthew M
authors.initials: MM
authors.lastname: Poggi
authors.forename: Glenn S
authors.initials: GS
authors.lastname: Kroog
authors.forename: Angelo
authors.initials: A
authors.lastname: Russo
authors.forename: Christine
authors.initials: C
authors.lastname: Muir
authors.forename: John
authors.initials: J
authors.lastname: Cook
authors.forename: Judith
authors.initials: J
authors.lastname: Smith
authors.forename: James B
authors.initials: JB
authors.lastname: Mitchell
authors.forename: Laurie L
authors.initials: LL
authors.lastname: Herscher
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D003841:Deoxycytidine / Q000008:administration & dosage* / Q000009:adverse effects / Q000031:analogs & derivatives*; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D010190:Pancreatic Neoplasms / Q000532:radiotherapy*; D011838:Radiation-Sensitizing Agents / Q000008:administration & dosage* / Q000009:adverse effects; D011879:Radiotherapy Dosage; D016019:Survival Analysis; D000093542:Gemcitabine
chemical_list: D011838:Radiation-Sensitizing Agents; D003841:Deoxycytidine; D000093542:Gemcitabine