Capecitabine: an evidence-based review of its effectiveness in the treatment of carcinoma of the pancreas

INTRODUCTION: More than 90% of patients with pancreatic cancer present either with incurable locally advanced or metastatic disease or relapse following surgery. For these patients systemic therapy offers the only prospect of salvage, but pancreatic cancer is one of the most chemoresistant of tumors; current chemotherapy can only delay progression in a limited proportion of patients and survival rates are poor. There is therefore a pressing need for more effective therapy. Capecitabine is a new oral prodrug of fluorouracil, which has shown activity in pancreatic cancer particularly when used in combination with gemcitabine. AIMS: To review the emerging evidence for the clinical effectiveness of capecitabine in the management of carcinoma of the pancreas. EVIDENCE REVIEW: There is evidence from phase II testing that capecitabine is active in pancreatic cancer. The Swiss Group for Clinical Cancer Research/Central European Cooperative Oncology Group (SAKK/CECOG) phase III trial found that the combination of gemcitabine and capecitabine did not improve overall median survival as compared with gemcitabine alone (8.4 vs 7.3 months, respectively; P=0.314) but subgroup analysis in patients with good performance score [Karnofsky Performance Scores (KPS) ≥90] revealed a significant survival improvement with the combination arm (10.1 months) compared with single-agent gemcitabine (7.5 months; P=0.033). Preliminary data from the GemCap phase III trial indicated significantly improved response rates and survival for the combination of gemcitabine with capecitabine (7.4 months) compared with gemcitabine alone (6 months; P=0.026) but analysis of the mature data with adequate follow-up awaits reporting. CLINICAL POTENTIAL: The addition of capecitabine to gemcitabine may represent a small step forward in the management of advanced pancreatic cancer but further data are required in order to determine its full impact.