Chemotherapy for Advanced Pancreatic Cancer

Kim, Tae You

Abstract

Pancreatic carcinoma constitutes to be a major unsolved health problems worldwide. Because of difficulties in diagnosis, the aggressiveness of pancreatic cancers, and the lack of effective systemic therapies, only less than 5% of patients with pancreatic cancer will be alive 5 years after diagnosis. At the time of diagnosis of pancreatic cancer, less than 20% of patients present with tumors that are confined to the pancreas, and therefore only 10~20% undergo resection with curative intent. The majority of patients present with locally advanced and metastatic disease, whose median survival is only 6~9 months and 3~6 months, respectively. The result of chemotherapy, mainly based on 5-FU, have documented low response rate and little impact on survival or quality of life. However, during the past 10 years, a real progress has been made in the area of chemotherapy for pancreatic cancer with the introduction of gemcitabine. Gemcitabine have shown improved overall survival (5.65 months vs. 4.41 months) and clinical benefit response (23.8% vs. 4.8%) compared with standard 5-FU-based chemotherapy. Therefore, gemcitabine has replaced 5-fluorouracil-based chemotherapy as the standard of care. Subsequent trials have also suggested that combinations of gemcitabine with other agents, such as cisplatin, irinotecan or capecitabine, may further improve clinical benefits in patients with advanced pancreatic cancers. One promising combination is gemcitabine plus oxaliplatin (GEMOX), that was reported in 2003. The response rate of GEMOX and gemcitabine alone was 25.8% and 16.1% (p=0.05). The time to progression was also significantly prolonged in GEMOX arm compared to gemctabine (25 weeks vs 16 weeks). In addition, other several efforts including alternative method of gemibitabine infusion as well as novel drug-combination have been made to improve the prognosis. Novel drugs include pemetrexed, S-1, cetuximab, and bevacizumab, etc. For instance, the response rate and 1-year survival of patients who treated with gemicitabine plus bevacizumab, a monoclonal blocking antibody of VEGF, was 38% and 54%, respectively. In conclusion, a shift in paradigms has occurred in the management of pancreatic cancer with respect to systemic therapy. The use of chemotherapy improved survival, reduced tumor-related symptoms, and achieved significant clinical benefit response in one third of patients. New targets for therapy through rapidly evolving understanding of the molecular biology of pancreatic cancer hold promise for even more effective treatment in the near future.