title: A phase I study of radiation therapy and twice-weekly gemcitabine and cisplatin in patients with locally advanced pancreatic cancer.
abstract: OBJECTIVE
  In vitro studies suggest that low-dose gemcitabine sensitizes cells to radiation therapy and that this effect persists for 48 h after drug exposure. Cisplatin is a radiation sensitizer and is also synergistic with gemcitabine in some in vitro tumor systems. Gemcitabine's radiosensitizing properties can theoretically be exploited by twice-weekly administration. This study assessed toxicity in patients with pancreatic cancer treated with radiation therapy, gemcitabine, and cisplatin.
  
  
  METHODS
  Patients with locally advanced pancreatic or gastric cancer were eligible. Gemcitabine and cisplatin were given twice weekly for 3 weeks during radiation therapy (50.4 Gy in 28 fractions). The starting dose of gemcitabine was 5 mg/m(2) i.v. The starting dose for cisplatin was 5 mg/m(2). Chemotherapy doses escalated every 3 to 6 patients according to a standard Phase I study design.
  
  
  RESULTS
  Twenty-four evaluable patients, all with pancreatic cancer, were treated on this protocol. Grade 3 neutropenia occurred in 2 patients, Grade 3 thrombocytopenia occurred in 2, and Grade 4 lymphopenia occurred in 1. There was no clear relationship between chemotherapy dose and hematologic toxicity. The most common Grade 3-4 nonhematologic toxic responses were vomiting (7 patients) and nausea (7 patients). Dose-limiting toxicity consisting of Grade 4 nausea and vomiting occurred in 2 of 3 patients at dose Level 6 (gemcitabine 45 mg/m(2) i.v. and cisplatin 10 mg/m(2) i.v.). Six patients were treated at dose Level 5 (gemcitabine 30 mg/m(2) i.v. and cisplatin 10 mg/m(2) i.v.) without dose-limiting toxicity.
  
  
  CONCLUSIONS
  Gemcitabine 30 mg/m(2) i.v. twice weekly and cisplatin 10 mg/m(2) i.v. twice weekly may be given concurrently with radiation therapy (50.4 Gy in 28 fractions) with acceptable toxicity.
authors.affiliation: Mayo Clinic, Rochester, MN 55905, USA.
authors.forename: James A
authors.initials: JA
authors.lastname: Martenson
authors.forename: Antonio P G
authors.initials: AP
authors.lastname: Vigliotti
authors.forename: Henry C
authors.initials: HC
authors.lastname: Pitot
authors.forename: Louis H
authors.initials: LH
authors.lastname: Geeraerts
authors.forename: Daniel J
authors.initials: DJ
authors.lastname: Sargent
authors.forename: Michael G
authors.initials: MG
authors.lastname: Haddock
authors.forename: Chirantan
authors.initials: C
authors.lastname: Ghosh
authors.forename: Michael D
authors.initials: MD
authors.lastname: Keppen
authors.forename: Tom R
authors.initials: TR
authors.lastname: Fitch
authors.forename: Richard M
authors.initials: RM
authors.lastname: Goldberg
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy / Q000401:mortality / Q000473:pathology / Q000532:radiotherapy* / Q000601:surgery; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D017024:Chemotherapy, Adjuvant; D002945:Cisplatin / Q000008:administration & dosage; D003131:Combined Modality Therapy; D003841:Deoxycytidine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology; D003967:Diarrhea / Q000209:etiology; D004334:Drug Administration Schedule; D005260:Female; D006402:Hematologic Diseases / Q000209:etiology; D006801:Humans; D015993:Life Tables; D008297:Male; D020714:Maximum Tolerated Dose; D008875:Middle Aged; D009325:Nausea / Q000209:etiology; D010180:Pancreatectomy; D010190:Pancreatic Neoplasms / Q000188:drug therapy / Q000401:mortality / Q000473:pathology / Q000532:radiotherapy* / Q000601:surgery; D011838:Radiation-Sensitizing Agents / Q000008:administration & dosage / Q000494:pharmacology; D016019:Survival Analysis; D016896:Treatment Outcome; D014839:Vomiting / Q000209:etiology; D000093542:Gemcitabine
chemical_list: D011838:Radiation-Sensitizing Agents; D003841:Deoxycytidine; D002945:Cisplatin; D000093542:Gemcitabine