title: Phase I study of concomitant gemcitabine and IMRT for patients with unresectable adenocarcinoma of the pancreatic head.
abstract: OBJECTIVE
  We hypothesized that dynamic intensity-modulated radiotherapy (IMRT) would protect normal tissues enough to allow the escalation of either the gemcitabine or radiotherapy dose in unresectable pancreatic cancer patients.
  
  
  METHODS
  The trial was designed to build on a previous phase I trial that determined the maximum tolerated dose (MTD) of gemcitabine (350 mg/m2) with concurrent radiotherapy (30 Gy/10 fractions). Only patients with unresectable disease based on established criteria were eligible. The plan was to alternate escalating the radiation dose by 3 Gy and the gemcitabine dose by 50 mg/m2. The starting dose of gemcitabine was 350 mg/m2 and 33 Gy/11 fractions of IMRT to the regional lymphatics and primary disease. The NCI Common Toxicity Criteria were used for dose-limiting toxicity (DLT).
  
  
  RESULTS
  All three patients in the first cohort treated suffered DLT. Therefore, a second cohort of patients received a lower gemcitabine dose (250 mg/m2). Both patients treated at this dose level experienced DLT. The DLTs were all due to myelosuppression and upper gastrointestinal toxicity. All patients required a gemcitabine dose reduction. Also, four patients required hospital admission for supportive care, while the fifth died of an unrelated cause shortly after completing therapy. The trial was then closed due to excessive toxicity.
  
  
  CONCLUSIONS
  Hypofractionated dynamic IMRT to the primary site and regional lymphatics did not permit escalation of either the radiation or gemcitabine dose. Dynamic IMRT requires further investigation before it can be applied to toxic combinations of chemotherapy and radiation in the upper abdomen.
authors.affiliation: Department of Radiation Oncology, The University of Texas M.D. Anderson Cancer Center, Houston, TX 77030, USA. ccrane@mdanderson.org
authors.forename: C H
authors.initials: CH
authors.lastname: Crane
authors.forename: J A
authors.initials: JA
authors.lastname: Antolak
authors.forename: I I
authors.initials: II
authors.lastname: Rosen
authors.forename: K M
authors.initials: KM
authors.lastname: Forster
authors.forename: D B
authors.initials: DB
authors.lastname: Evans
authors.forename: N A
authors.initials: NA
authors.lastname: Janjan
authors.forename: C
authors.initials: C
authors.lastname: Charnsangavej
authors.forename: P W
authors.initials: PW
authors.lastname: Pisters
authors.forename: R
authors.initials: R
authors.lastname: Lenzi
authors.forename: M A
authors.initials: MA
authors.lastname: Papagikos
authors.forename: R A
authors.initials: RA
authors.lastname: Wolff
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy* / Q000473:pathology / Q000532:radiotherapy*; D000368:Aged; D000964:Antimetabolites, Antineoplastic / Q000008:administration & dosage* / Q000009:adverse effects / Q000627:therapeutic use; D015331:Cohort Studies; D003131:Combined Modality Therapy; D003841:Deoxycytidine / Q000008:administration & dosage* / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D019583:Dose Fractionation, Radiation; D005260:Female; D006801:Humans; D008297:Male; D020714:Maximum Tolerated Dose; D008875:Middle Aged; D009367:Neoplasm Staging; D010190:Pancreatic Neoplasms / Q000188:drug therapy* / Q000473:pathology / Q000532:radiotherapy*; D000093542:Gemcitabine
chemical_list: D000964:Antimetabolites, Antineoplastic; D003841:Deoxycytidine; D000093542:Gemcitabine