Phase 2 Study of Erlotinib Combined With Adjuvant Chemoradiation and Chemotherapy in Patients With Resectable Pancreatic Cancer

• Published in: International journal of radiation oncology, biology, physics Vol. 86; no. 4; pp. 678 - 685
• Main Authors: Herman, Joseph M., MD, MSc, Fan, Katherine Y., BS, Wild, Aaron T., BA, Hacker-Prietz, Amy, MS, PA-C, Wood, Laura D., MD, PhD, Blackford, Amanda L., ScM, Ellsworth, Susannah, MD, Zheng, Lei, MD, Le, Dung T., MD, De Jesus-Acosta, Ana, MD, Hidalgo, Manuel, MD, PhD, Donehower, Ross C., MD, Schulick, Richard D., MD, MBA, Edil, Barish H., MD, Choti, Michael A., MD, Hruban, Ralph H., MD, Pawlik, Timothy M., MD, MPH, PhD, Cameron, John L., MD, Laheru, Daniel A., MD, Wolfgang, Christopher L., MD, PhD
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 15.07.2013
• Subjects: Aged; Aged, 80 and over; Analysis of Variance; Antineoplastic Agents - administration & dosage; Antineoplastic Agents - adverse effects; Antineoplastic Agents - therapeutic use; Antineoplastic Combined Chemotherapy Protocols - therapeutic use; Capecitabine; Carcinoma, Pancreatic Ductal - mortality; Carcinoma, Pancreatic Ductal - pathology; Carcinoma, Pancreatic Ductal - therapy; CARCINOMAS; Chemoradiotherapy, Adjuvant - adverse effects; Chemoradiotherapy, Adjuvant - methods; CHEMOTHERAPY; Deoxycytidine - administration & dosage; Deoxycytidine - analogs & derivatives; DERMATITIS; Dose Fractionation; Drug Eruptions - etiology; Drug Eruptions - pathology; Erlotinib Hydrochloride; Female; Fluorouracil - administration & dosage; Fluorouracil - analogs & derivatives; Hematology, Oncology and Palliative Medicine; Humans; LYMPH NODES; Male; METASTASES; Middle Aged; MULTIVARIATE ANALYSIS; Neoplasm Recurrence, Local; PANCREAS; Pancreatectomy; Pancreatic Neoplasms - mortality; Pancreatic Neoplasms - pathology; Pancreatic Neoplasms - therapy; Pancreaticoduodenectomy; PATIENTS; Quality of Life; Quinazolines - administration & dosage; Quinazolines - adverse effects; Quinazolines - therapeutic use; Radiology; RADIOLOGY AND NUCLEAR MEDICINE; RADIOTHERAPY; Radiotherapy, Intensity-Modulated; TOXICITY
• ISSN: 0360-3016; 1879-355X
• DOI: 10.1016/j.ijrobp.2013.03.032

Purpose 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 and Materials Forty-eight patients with resected PDAC received adjuvant erlotinib (100 mg daily) and capecitabine (800 mg/m2 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/m2 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. Conclusion 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.