title: Phase I/II trial of hyperfractionated accelerated chemoradiotherapy for unresectable advanced pancreatic cancer.
abstract: BACKGROUND
  We conducted a Phase I/II study to evaluate the local efficacy and toxicity of hyperfractionated accelerated radiotherapy (HART) combined with 5-fluorouracil (5-FU) and cisplatin (CDDP) in patients with unresectable advanced pancreatic cancer.
  
  
  METHODS
  Thirty-five patients (15 with Stage 4A and 20 with Stage 4B disease according to TNM classification) were enrolled between August 1997 and August 2001 into this Phase I/II trial. All patients received concurrent HART (1.5 Gy twice daily separated by 6 h for 5 days per week), 5-FU (375 mg/m(2) given as continuous intravenous infusion), and CDDP (2 mg/m(2) given as 30-min infusion just before each fraction of irradiation). In the Phase I trial, the total dose of radiation was escalated from 27 to 45 Gy.
  
  
  RESULTS
  Twenty-one patients were enrolled in the Phase I study and six patients were given the final planned dose (45 Gy) which did not exceed the maximum tolerated dose. Eleven patients (52.4%) suffered from Grade 3 or worse neutropenia. Vomiting and mucositis were observed in 21 (100%) and 12 (57.1%) patients, respectively. An additional 14 patients were entered in the Phase II trial and received a total dose of 45 Gy, which is recommended in Phase I trial. Concerning the local tumor control of 20 patients with the recommended regimen, 7 patients (35%) achieved partial response, 10 (50%) remained stable and local progressive disease occurred in 3 (15%). The median survival time and the overall 1-year survival rate were 11.2 months and 40.0%, respectively, in 20 patients who received the recommended regimen. In Stage 4A patients, they were 13.0 months and 70.0%, respectively. The trend of toxicities in patients with the recommended regimen was almost the same as that observed in the Phase I study.
  
  
  CONCLUSIONS
  The chosen combined modality treatment was well tolerated, and showed an expected local efficacy for the treatment of unresectable advanced pancreatic cancer.
authors.affiliation: Department of Surgery and Clinical Oncology, Osaka University, Suita, Osaka, Japan.
authors.forename: Masanori
authors.initials: M
authors.lastname: Tsujie
authors.forename: Shoji
authors.initials: S
authors.lastname: Nakamori
authors.forename: Eiichi
authors.initials: E
authors.lastname: Tanaka
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Nagano
authors.forename: Koji
authors.initials: K
authors.lastname: Umeshita
authors.forename: Keizo
authors.initials: K
authors.lastname: Dono
authors.forename: Masato
authors.initials: M
authors.lastname: Sakon
authors.forename: Takehiro
authors.initials: T
authors.lastname: Inoue
authors.forename: Toshihiko
authors.initials: T
authors.lastname: Inoue
authors.forename: Morito
authors.initials: M
authors.lastname: Monden
mesh_terms: D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000627:therapeutic use*; D002945:Cisplatin / Q000008:administration & dosage; D003131:Combined Modality Therapy; D019583:Dose Fractionation, Radiation; D004334:Drug Administration Schedule; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage; D006801:Humans; D008297:Male; D020714:Maximum Tolerated Dose; D008875:Middle Aged; D009367:Neoplasm Staging; D009503:Neutropenia / Q000209:etiology; D010190:Pancreatic Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology / Q000532:radiotherapy*; D012074:Remission Induction; D015996:Survival Rate; D013921:Thrombocytopenia / Q000209:etiology
chemical_list: D002945:Cisplatin; D005472:Fluorouracil