title: Estimating optimal dose of twice-weekly gemcitabine for concurrent chemoradiotherapy in unresectable pancreatic carcinoma: mature results of GEMRT-01 Phase I trial.
abstract: OBJECTIVE
  To accurately determine the maximal tolerated dose, feasibility, and antitumor activity of concurrent chemoradiotherapy including twice-weekly gemcitabine in patients with unresectable pancreatic adenocarcinoma.
  
  
  METHODS
  Eligible patients with histologically proven adenocarcinoma of the pancreas were included in this Phase I trial. Radiotherapy was delivered to a total dose of 50 Gy. Concurrent chemotherapy with twice-weekly gemcitabine was administered during the 5 weeks of radiotherapy, from an initial dose of 30 mg/m(2). The gemcitabine doses were escalated in 10-mg/m(2) increments in a three-plus-three design, until dose-limiting toxicities were observed.
  
  
  RESULTS
  A total of 35 patients were included in the trial. The feasibility of chemoradiotherapy was high, because all the patients received the planned total radiation dose, and 26 patients (74%) received > or = 70% of the planned chemotherapy dose. The mean total delivered dose of gemcitabine was 417 mg/m(2) (i.e., 77% of the prescribed dose). The maximal tolerated dose of twice-weekly gemcitabine was 70 mg/m(2). Of the 35 patients, 13 had a partial response (37%) and 21 had stable disease (60%). Overall, the median survival and the 6-, 12-, and 18-month survival rates were 10.6 months and 82%, 31%, and 11%, respectively. Survival was significantly longer in patients with an initial performance status of 0 or 1 (p = .004).
  
  
  CONCLUSIONS
  Our mature data have indicated that gemcitabine doses can be increased < or = 70 mg/m(2), when delivered twice-weekly with concurrent radiotherapy. This combination shows promises to achieve better recurrence-free and overall survival. These results will serve as a basis for further implementation of the multimodal treatment of locally advanced pancreatic carcinoma.
authors.affiliation: Department of Radiotherapy-Oncology, Centre Hospitalier Lyon-Sud, Hospices Civils de Lyon, Lyon, France.
authors.forename: Nicolas
authors.initials: N
authors.lastname: Girard
authors.forename: Françoise
authors.initials: F
authors.lastname: Mornex
authors.forename: Nadine
authors.initials: N
authors.lastname: Bossard
authors.forename: Marc
authors.initials: M
authors.lastname: Ychou
authors.forename: Bruno
authors.initials: B
authors.lastname: Chauffert
authors.forename: Virginie
authors.initials: V
authors.lastname: Wautot
mesh_terms: D000328:Adult; D000368:Aged; D000964:Antimetabolites, Antineoplastic / Q000008:administration & dosage* / Q000009:adverse effects; D003131:Combined Modality Therapy / Q000379:methods; D003841:Deoxycytidine / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives*; D004334:Drug Administration Schedule; D005240:Feasibility Studies; D005260:Female; D006801:Humans; D008297:Male; D020714:Maximum Tolerated Dose; D008875:Middle Aged; D009503:Neutropenia / Q000139:chemically induced; D010190:Pancreatic Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology / Q000532:radiotherapy*; D011879:Radiotherapy Dosage; D015996:Survival Rate; D013921:Thrombocytopenia / Q000139:chemically induced; D047368:Tumor Burden; D055815:Young Adult; D000093542:Gemcitabine
chemical_list: D000964:Antimetabolites, Antineoplastic; D003841:Deoxycytidine; D000093542:Gemcitabine