title: Combined radiochemotherapy of locally advanced unresectable pancreatic adenocarcinoma with mitomycin C plus 24-hour continuous infusional gemcitabine.
abstract: BACKGROUND
  In locally advanced pancreatic cancer, the combination of chemotherapy with radiotherapy is gaining increasing importance; although, in view of the reported long-term results of several contemporary trials, further improvements are certainly warranted. The aim of the present study was to evaluate the effectiveness and safety of a combined-treatment modality consisting of systemic chemotherapy with 24-h continuous infusional gemcitabine and mitomycin C, plus external beam radiotherapy in patients with localized unresectable adenocarcinoma of the pancreas.
  
  
  METHODS
  Systemic chemotherapy consisted of mitomycin C 8 mg/m2 given as i.v. bolus injection on day 1 and gemcitabine administered as a 24-h continous infusion once weekly for 3 of 4 weeks. The starting dose of gemcitabine was 100 mg/m2 and dose levels were escalated in consecutive cohorts of 3-6 patients to 130 and 160 mg/m2, utilizing an escalating-dose Phase I trial design. Radiation therapy using megavolt irradiation (total dose, 45 Gy, 1.8 Gy/day) of 6 MV photons or greater with a 3- or 4-field technique was delivered concurrently for 5-6 weeks.
  
  
  RESULTS
  Between January 1997 and August 1998, a total of 15 patients were enrolled in this trial, all of whom were assessable for toxicity, response, and survival. The dose-limiting toxicities at the 160 mg/m2 gemcitabine level were myelosuppression, specifically neutropenia +/- thrombocytopenia, and gastrointestinal symptoms, including stomatitis, vomiting, and diarrhea. Only 1 partial response was observed (7%), and disease was stabilized in 10 additional patients (67%). The median time to progression was 5.5 months (range, 2-12 months). Whereas all patients developed distant metastases, locoregional failure occurred in only 3. The median survival time was 8.3 months (range, 2.5 to 22.0+ months), and the 1-year survival rate was 13.3%.
  
  
  CONCLUSIONS
  The MTD of gemcitabine when given as prolonged infusion in combination with mitomycin C and radiation therapy was 130 mg/m2/week. Therapeutic results suggest that combined chemoradiation with this regimen is feasible and effective for local control of pancreatic cancer, but essentially ineffective in counteracting metastatic tumor growth.
authors.affiliation: Division of Oncology, Department of Internal Medicine I, Vienna University Medical School, Waeringer Guertel 18-20, A-1090 Vienna, Austria. gabriela.kornek@unievie.ac.at
authors.forename: G V
authors.initials: GV
authors.lastname: Kornek
authors.forename: R
authors.initials: R
authors.lastname: Pötter
authors.forename: E
authors.initials: E
authors.lastname: Selzer
authors.forename: A
authors.initials: A
authors.lastname: Schratter
authors.forename: H
authors.initials: H
authors.lastname: Ulrich-Pur
authors.forename: M
authors.initials: M
authors.lastname: Rogy
authors.forename: G
authors.initials: G
authors.lastname: Kraus
authors.forename: W
authors.initials: W
authors.lastname: Scheithauer
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy* / Q000473:pathology / Q000532:radiotherapy*; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D003131:Combined Modality Therapy; D003841:Deoxycytidine / Q000008:administration & dosage / Q000031:analogs & derivatives; D005260:Female; D006801:Humans; D007275:Injections, Intravenous; D007970:Leukopenia / Q000209:etiology; D008297:Male; D008875:Middle Aged; D016685:Mitomycin / Q000008:administration & dosage; D009367:Neoplasm Staging; D009503:Neutropenia / Q000209:etiology; D010190:Pancreatic Neoplasms / Q000188:drug therapy* / Q000473:pathology / Q000532:radiotherapy*; D016019:Survival Analysis; D013921:Thrombocytopenia / Q000209:etiology; D000093542:Gemcitabine
chemical_list: D003841:Deoxycytidine; D016685:Mitomycin; D000093542:Gemcitabine