title: Phase II study of gemcitabine and erlotinib as adjuvant therapy for patients with resected pancreatic cancer.
abstract: BACKGROUND
  There is currently no consensus about the most effective adjuvant therapy for adenocarcinoma of the pancreas. Both gemcitabine and erlotinib have been demonstrated to improve survival in patients with metastatic disease. This study was designed to evaluate the efficacy of gemcitabine and erlotinib as adjuvant therapy, and to explore potential biomarkers associated with response.
  
  
  METHODS
  An institutional review board-approved single-center phase II trial of adjuvant biweekly fixed-dose rate gemcitabine (1500 mg/m(2)) and daily erlotinib (150 mg/day) for 4 months followed by maintenance erlotinib (150 mg/day) over 8 months was initiated. Primary end point was recurrence-free survival (RFS). Epidermal growth factor receptor (EGFR) expression in the resected tumors was assessed by fluorescence in situ hybridization (FISH) and immunohistochemistry (IHC).
  
  
  RESULTS
  The study completed planned accrual of 25 patients. Median follow-up was 18.2 (range 11.6-23.5) months. Recurrences were observed in 17 subjects (68%). Median RFS was 14.0 months (95% confidence interval [95% CI], 8.2-24.5) with 1-year and 2-year RFS of 56% (95% CI, 35-73) and 26% (95% CI, 6-52), respectively. Median overall survival was not reached. Estimated 1-year and 2-year overall survival was 84% (95% CI, 63-94) and 53% (95% CI, 22-76), respectively. Nine patients (36%) had a grade 3 event and only 1 (4%) had a grade 4 (neutropenia). Most toxicities were dermatologic, gastrointestinal, and constitutional. There were nonsignificant trends to longer RFS and lower recurrence rates while receiving therapy in subjects with fluorescence in situ hybridization-positive tumors and greater immunohistochemistry expression.
  
  
  CONCLUSIONS
  Our phase II results suggest that adjuvant gemcitabine and erlotinib is a promising regimen that merits further investigation.
authors.affiliation: Department of Surgery, Stony Brook University Hospital, Stony Brook, NY, USA.
authors.forename: Philip Q
authors.initials: PQ
authors.lastname: Bao
authors.forename: Ramesh K
authors.initials: RK
authors.lastname: Ramanathan
authors.forename: Alyssa
authors.initials: A
authors.lastname: Krasinkas
authors.forename: Nathan
authors.initials: N
authors.lastname: Bahary
authors.forename: Barry C
authors.initials: BC
authors.lastname: Lembersky
authors.forename: David L
authors.initials: DL
authors.lastname: Bartlett
authors.forename: Steven J
authors.initials: SJ
authors.lastname: Hughes
authors.forename: Kenneth K
authors.initials: KK
authors.lastname: Lee
authors.forename: A James
authors.initials: AJ
authors.lastname: Moser
authors.forename: Herbert J
authors.initials: HJ
authors.lastname: Zeh
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy* / Q000556:secondary / Q000601:surgery; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D017024:Chemotherapy, Adjuvant; D003841:Deoxycytidine / Q000008:administration & dosage / Q000031:analogs & derivatives; D066246:ErbB Receptors / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D000069347:Erlotinib Hydrochloride; D005260:Female; D006801:Humans; D007124:Immunoenzyme Techniques; D017404:In Situ Hybridization, Fluorescence; D008297:Male; D008875:Middle Aged; D010180:Pancreatectomy; D010190:Pancreatic Neoplasms / Q000188:drug therapy* / Q000473:pathology / Q000601:surgery; D011799:Quinazolines / Q000008:administration & dosage; D015996:Survival Rate; D016896:Treatment Outcome; D000093542:Gemcitabine
chemical_list: D011799:Quinazolines; D003841:Deoxycytidine; D000069347:Erlotinib Hydrochloride; C512478:EGFR protein, human; D066246:ErbB Receptors; D000093542:Gemcitabine