title: Radiation therapy and concurrent fixed dose amifostine with escalating doses of twice-weekly gemcitabine in advanced pancreatic cancer.
abstract: OBJECTIVE
  To determine the maximum tolerated dose (MTD) and dose-limiting toxicity (DLT) of twice-weekly gemcitabine (TW-G) when administered in conjunction with fixed dose amifostine (A) during external radiotherapy (RT) in patients with advanced pancreatic cancer.
  
  
  METHODS
  Ten patients with previously untreated, locally advanced, or asymptomatic-metastatic pancreatic adenocarcinoma were enrolled in this study. RT was delivered by using the standard four-field technique (1.8 Gy daily fractions, 45 Gy followed by a boost of 5.4 Gy, in 5-1/2 weeks). The starting dose of TW-G was 60 mg/m(2) (i.v., 30-min infusion), which is equal to the upper limit of previously reported MTD of TW-G when given without A during RT. A was given just before the TW-G, at a fixed dose of 340 mg/m(2) (i.v., rapid infusion). TW-G doses were escalated by 30-mg/m(2) increments in successive cohorts of 3 to 6 additional patients until DLT was observed. Toxicities were graded using the Radiation Therapy Oncology Group and National Cancer Institute Common Toxicity Criteria, version 2.0.
  
  
  RESULTS
  In general, therapy was well tolerated in patients treated at the first two dose levels of 60 mg/m(2) and 90 mg/m(2). The DLT of TW-G given in conjunction with A during RT were neutropenia, thrombocytopenia, and nausea/vomiting at the dose level of 120 mg/m(2). Of the 10 patients eligible for a median follow-up of 10 months, 5 remain alive; 1 complete responder, 3 partial responders, and 1 with stable disease.
  
  
  CONCLUSIONS
  A dose of TW-G at a level of 90 mg/m(2) produced tolerable toxicity and it may possess significant activity when delivered in conjunction with 340 mg/m(2) dose of A during RT of the upper abdomen. Due to the higher MTD of TW-G seen in our study, we consider that the A supplementation may optimize the therapeutic index of TW-G-based chemoradiotherapy protocols in patients with pancreatic carcinoma.
authors.affiliation: Department of Radiation Oncology, Karadeniz Technical University, Faculty of Medicine, Trabzon, Turkey. ayavuz@gul.net.tr
authors.forename: A A
authors.initials: AA
authors.lastname: Yavuz
authors.forename: F
authors.initials: F
authors.lastname: Aydin
authors.forename: M N
authors.initials: MN
authors.lastname: Yavuz
authors.forename: E
authors.initials: E
authors.lastname: Ilis
authors.forename: F
authors.initials: F
authors.lastname: Ozdemir
mesh_terms: D000230:Adenocarcinoma / Q000473:pathology / Q000532:radiotherapy*; D000328:Adult; D000368:Aged; D004999:Amifostine / Q000008:administration & dosage* / Q000009:adverse effects; D000964:Antimetabolites, Antineoplastic / Q000008:administration & dosage* / Q000009:adverse effects; D003841:Deoxycytidine / Q000008:administration & dosage* / Q000009:adverse effects / Q000031:analogs & derivatives*; D018450:Disease Progression; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009325:Nausea / Q000139:chemically induced; D009503:Neutropenia / Q000139:chemically induced; D010190:Pancreatic Neoplasms / Q000473:pathology / Q000532:radiotherapy*; D011837:Radiation-Protective Agents / Q000008:administration & dosage* / Q000009:adverse effects; D011838:Radiation-Sensitizing Agents / Q000008:administration & dosage* / Q000009:adverse effects; D016019:Survival Analysis; D013921:Thrombocytopenia / Q000139:chemically induced; D014839:Vomiting / Q000139:chemically induced; D000093542:Gemcitabine
chemical_list: D000964:Antimetabolites, Antineoplastic; D011837:Radiation-Protective Agents; D011838:Radiation-Sensitizing Agents; D003841:Deoxycytidine; D004999:Amifostine; D000093542:Gemcitabine