A phase I/II study of radiochemotherapy in extrahepatic bile duct carcinoma

Abstract

4233 Background: The 5-year survival rate of patients with curatively resected extrahepatic bile duct carcinoma is less than 25%. Despite the poor prognosis there is a lack of adjuvant therapies. Phase II trials demonstrated that advanced extrahepatic bile duct carcinomas respond to both chemotherapy with gemcitabine and radiotherapy. Our objective was to define a feasible and effective radiochemotherapy in bile duct cancer. Methods: Patients with histologically confirmed adenocarcinoma of the distal or hilar extrahepatic bile ducts were prospectively enrolled after non-curative operations (R1/R2-resection or surgical exploration). Treatment consisted of a fractionated radiotherapy with 40 Gy + 9.6 Gy Boost accompanied by gemcitabine 100 mg/m2 weekly x 5. After a two week rest gemcitabine (1000 mg/m2 IV weekly x 2 q3w) and capecitabine (1500 mg/m2 PO D1–14 q3w) were given. Treatment continued for 6 cycles in nonmeasurable disease or until disease progression or intolerable toxicity. Primary endpoint was toxicity; secondary endpoints were response rate in measurable disease and overall survival. Results: 11 Patients (hilar/distal carcinoma: 8/3) were enrolled. Radiotherapy was completed in all patients and a total of 49 cycles of chemotherapy were applied. Grade 3/4 toxicity was observed in 7 patients and consisted of leucopenia (2 cycles), thrombopenia (1), nausea (3), a bleeding ulcer (1) and cachexia in 3 patients. The most frequent mild toxicities were asthenia and nausea in 50% and 40% of cycles, respectively. Therapy was discontinued in 2 patients. Of 8 patients with measurable disease, one each had a complete and a partial response and 3 had stable disease for at least 3 months. Median actuarial survival is 296 days. Conclusions: Radiochemotherapy with gemcitabine followed by gemcitabine and capecitabine is an active regimen with manageable toxicity in postoperative palliative treatment of extrahepatic bile duct cancer. No significant financial relationships to disclose.