title: Phase 2 study of erlotinib combined with adjuvant chemoradiation and chemotherapy in patients with resectable pancreatic cancer.
abstract: OBJECTIVE
  Long-term survival rates for patients with resected pancreatic ductal adenocarcinoma (PDAC) have stagnated at 20% for more than a decade, demonstrating the need to develop novel adjuvant therapies. Gemcitabine-erlotinib therapy has demonstrated a survival benefit for patients with metastatic PDAC. Here we report the first phase 2 study of erlotinib in combination with adjuvant chemoradiation and chemotherapy for resected PDAC.
  
  
  METHODS
  Forty-eight patients with resected PDAC received adjuvant erlotinib (100 mg daily) and capecitabine (800 mg/m(2) twice daily Monday-Friday) concurrently with intensity modulated radiation therapy (IMRT), 50.4 Gy over 28 fractions followed by 4 cycles of gemcitabine (1000 mg/m(2) on days 1, 8, and 15 every 28 days) and erlotinib (100 mg daily). The primary endpoint was recurrence-free survival (RFS).
  
  
  RESULTS
  The median follow-up time was 18.2 months (interquartile range, 13.8-27.1). Lymph nodes were positive in 85% of patients, and margins were positive in 17%. The median RFS was 15.6 months (95% confidence interval [CI], 13.4-17.9), and the median overall survival (OS) was 24.4 months (95% CI, 18.9-29.7). Multivariate analysis with adjustment for known prognostic factors showed that tumor diameter >3 cm was predictive for inferior RFS (hazard ratio, 4.01; P=.001) and OS (HR, 4.98; P=.02), and the development of dermatitis was associated with improved RFS (HR, 0.27; P=.009). During CRT and post-CRT chemotherapy, the rates of grade 3/4 toxicity were 31%/2% and 35%/8%, respectively.
  
  
  CONCLUSIONS
  Erlotinib can be safely administered with adjuvant IMRT-based CRT and chemotherapy. The efficacy of this regimen appears comparable to that of existing adjuvant regimens. Radiation Therapy Oncology Group 0848 will ultimately determine whether erlotinib produces a survival benefit in patients with resected pancreatic cancer.
authors.affiliation: Department of Radiation Oncology and Molecular Radiation Sciences, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins School of Medicine, Baltimore, Maryland 21231, USA. jherma15@jhmi.edu
authors.forename: Joseph M
authors.initials: JM
authors.lastname: Herman
authors.forename: Katherine Y
authors.initials: KY
authors.lastname: Fan
authors.forename: Aaron T
authors.initials: AT
authors.lastname: Wild
authors.forename: Amy
authors.initials: A
authors.lastname: Hacker-Prietz
authors.forename: Laura D
authors.initials: LD
authors.lastname: Wood
authors.forename: Amanda L
authors.initials: AL
authors.lastname: Blackford
authors.forename: Susannah
authors.initials: S
authors.lastname: Ellsworth
authors.forename: Lei
authors.initials: L
authors.lastname: Zheng
authors.forename: Dung T
authors.initials: DT
authors.lastname: Le
authors.forename: Ana
authors.initials: A
authors.lastname: De Jesus-Acosta
authors.forename: Manuel
authors.initials: M
authors.lastname: Hidalgo
authors.forename: Ross C
authors.initials: RC
authors.lastname: Donehower
authors.forename: Richard D
authors.initials: RD
authors.lastname: Schulick
authors.forename: Barish H
authors.initials: BH
authors.lastname: Edil
authors.forename: Michael A
authors.initials: MA
authors.lastname: Choti
authors.forename: Ralph H
authors.initials: RH
authors.lastname: Hruban
authors.forename: Timothy M
authors.initials: TM
authors.lastname: Pawlik
authors.forename: John L
authors.initials: JL
authors.lastname: Cameron
authors.forename: Daniel A
authors.initials: DA
authors.lastname: Laheru
authors.forename: Christopher L
authors.initials: CL
authors.lastname: Wolfgang
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000704:Analysis of Variance; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D000069287:Capecitabine; D021441:Carcinoma, Pancreatic Ductal / Q000401:mortality / Q000473:pathology / Q000628:therapy*; D059186:Chemoradiotherapy, Adjuvant / Q000009:adverse effects / Q000379:methods*; D003841:Deoxycytidine / Q000008:administration & dosage / Q000031:analogs & derivatives; D019583:Dose Fractionation, Radiation; D003875:Drug Eruptions / Q000209:etiology / Q000473:pathology; D000069347:Erlotinib Hydrochloride; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage / Q000031:analogs & derivatives; D006801:Humans; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local; D010180:Pancreatectomy; D010190:Pancreatic Neoplasms / Q000401:mortality / Q000473:pathology / Q000628:therapy*; D016577:Pancreaticoduodenectomy; D011788:Quality of Life; D011799:Quinazolines / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D050397:Radiotherapy, Intensity-Modulated; D000093542:Gemcitabine
chemical_list: D000970:Antineoplastic Agents; D011799:Quinazolines; D003841:Deoxycytidine; D000069287:Capecitabine; D000069347:Erlotinib Hydrochloride; D005472:Fluorouracil; D000093542:Gemcitabine