title: Phase I study of conformal radiotherapy and concurrent full-dose gemcitabine with erlotinib for unresected pancreatic cancer.
abstract: OBJECTIVE
  To determine the recommended dose of radiotherapy when combined with full-dose gemcitabine and erlotinib for unresected pancreas cancer.
  
  
  METHODS
  Patients with unresected pancreatic cancer (Zubrod performance status 0-2) were eligible for the present study. Gemcitabine was given weekly for 7 weeks (1,000 mg/m(2)) with erlotinib daily for 8 weeks (100 mg). A final toxicity assessment was performed in Week 9. Radiotherapy (starting at 30 Gy in 2-Gy fractions, 5 d/wk) was given to the gross tumor plus a 1-cm margin starting with the first dose of gemcitabine. A standard 3 plus 3 dose escalation (an additional 4 Gy within 2 days for each dose level) was used, except for the starting dose level, which was scheduled to contain 6 patients. In general, Grade 3 or greater gastrointestinal toxicity was considered a dose-limiting toxicity, except for Grade 3 anorexia or Grade 3 fatigue alone.
  
  
  RESULTS
  A total of 20 patients were treated (10 men and 10 women). Nausea, vomiting, and infection were significantly associated with the radiation dose (p = .01, p = .03, and p = .03, respectively). Of the 20 patients, 5 did not complete treatment and were not evaluable for dose-escalation purposes (3 who developed progressive disease during treatment and 2 who electively discontinued it). Dose-limiting toxicity occurred in none of 6 patients at 30 Gy, 2 of 6 at 34 Gy, and 1 of 3 patients at 38 Gy.
  
  
  CONCLUSIONS
  The results of the present study have indicated that the recommended Phase II dose is 30 Gy in 15 fractions.
authors.affiliation: Department of Radiation Oncology, William Beaumont Hospital, Royal Oak, MI 48073, USA. jrobertson@beaumont.edu
authors.forename: John M
authors.initials: JM
authors.lastname: Robertson
authors.forename: Jeffrey
authors.initials: J
authors.lastname: Margolis
authors.forename: Robert P
authors.initials: RP
authors.lastname: Jury
authors.forename: Savitha
authors.initials: S
authors.lastname: Balaraman
authors.forename: Matthew B
authors.initials: MB
authors.lastname: Cotant
authors.forename: Samer
authors.initials: S
authors.lastname: Ballouz
authors.forename: Iqbal G
authors.initials: IG
authors.lastname: Boxwala
authors.forename: Ishmael A
authors.initials: IA
authors.lastname: Jaiyesimi
authors.forename: Laura
authors.initials: L
authors.lastname: Nadeau
authors.forename: Maria
authors.initials: M
authors.lastname: Hardy-Carlson
authors.forename: Kimberly S
authors.initials: KS
authors.lastname: Marvin
authors.forename: Michelle
authors.initials: M
authors.lastname: Wallace
authors.forename: Hong
authors.initials: H
authors.lastname: Ye
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000964:Antimetabolites, Antineoplastic / Q000008:administration & dosage* / Q000009:adverse effects; D003841:Deoxycytidine / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives*; D004334:Drug Administration Schedule; D004359:Drug Therapy, Combination / Q000379:methods; D000069347:Erlotinib Hydrochloride; D005260:Female; D006801:Humans; D007239:Infections / Q000209:etiology; D008297:Male; D020714:Maximum Tolerated Dose; D008875:Middle Aged; D009325:Nausea / Q000209:etiology; D010190:Pancreatic Neoplasms / Q000188:drug therapy* / Q000473:pathology / Q000532:radiotherapy*; D011799:Quinazolines / Q000008:administration & dosage* / Q000009:adverse effects; D011838:Radiation-Sensitizing Agents / Q000008:administration & dosage* / Q000009:adverse effects; D011879:Radiotherapy Dosage; D020266:Radiotherapy, Conformal / Q000009:adverse effects / Q000379:methods*; D013997:Time Factors; D047368:Tumor Burden / Q000528:radiation effects; D014839:Vomiting / Q000209:etiology; D000093542:Gemcitabine
chemical_list: D000964:Antimetabolites, Antineoplastic; D011799:Quinazolines; D011838:Radiation-Sensitizing Agents; D003841:Deoxycytidine; D000069347:Erlotinib Hydrochloride; D000093542:Gemcitabine