Pancreatic Cancer
In the United States, pancreatic cancer is the third most common malignant tumor of the gastrointestinal tract and the fifth leading cause of cancer related mortality. The disease is often difficult to diagnose, especially in its early stages. Cancers of the exocrine pancreas are almost always fatal; nearly all patients die within two years of diagnosis. Most cancers arise in the head of the pancreas, eventually causing bile duct obstruction, pain, and clinical jaundice. Cancers arising in either the body or tail of the pancreas are insidious in their development and often far advanced when first detected. Most cancers are adenocarcinomas that originate from the pancreatic ducts. Surgical resection remains the only potentially curative approach. Staging depends on the size and extent of the primary tumor.
Pancreatic Cancer Treatment Summaries
Postoperative combined modality chemo/radiation therapy
Pancreatic cancer has the worst survival statistics of all the cancers and has the fourth highest death rate. Median survival is approximately 18 months for resected disease and 6 to 9 months for locally advanced or metastatic disease. Surgical resection only results in 10-20% long term survival. The majority of the recurrences are either loco-regional or hepatic and occur within the first 18 months post-resection. The addition of chemo-radiation therapy programs have decreased the recurrence risk and improved the median survival to 20+ months. The postoperative combined modality chemo/radiation therapy programs have been the standard therapy in the US. More recently the European studies have shown benefit for administration of adjuvant Gemcitabine based therapy in resected pancreatic cancer. This includes the ESPAC-1 trial which showed benefit for the 5FU/LV given for six months post resection. The second trial presented by Neuhaus showed benefit for single agent Gemcitabine given adjuvantly for six months post resection. Some of the newer trials are attempting to answer the questions related to the most effective way to administer the chemotherapy and radiotherapy post surgery.
Therapy for metastatic pancreatic disease is also evolving. Gemcitabine was approved by the FDA for treatment of advanced pancreatic cancer in 1998 and since that time there has been a lot of interest in making the therapy more effective by combining additional agents with Gemcitabine. This has included the Flouropyrimidines, Irinotecan, platinum analogs such as Cisplatin/Oxaliplatin, biologic agents Tipifarnib, Erlotinib, etc. Recent studies have shown some advantage for Gem + Oxaliplatin, Gem + Cisplatin containing regimens especially for patients with good performance status. The combination of Gemcitabine + the EGFR inhibitor Erlotinib (Tarceva) is another promising approach that showed survival advantage for the combination arm at one year.
References:
- Neoptolemos et al. A randomized trial of chemoradiotherapy and chemotherapy after resection of Pancreatic cancer. NEJM 2004, 350; 1200-10.
- Neuhaus, P. Gemcitabine as adjuvant therapy for resected pancreatic cancer. PASCO 2005. LBA # 4013.
- Burris HA, Moore MJ, Anderson J, et al: Improvements in survival and clinical benefit with gemcitabine as first-line therapy for patients with advanced pancreatic cancer: A randomized trial. J Clin Oncol 15:2403-2413, 1997.
- Louvet et al. Gemcitabine in combination with Oxaliplatin compared with Gemcitabine alone in locally advanced or metastatic Pancreatic Cancer: Results of a GERCOR/GISCAD phase III trial. JCO 23:3509-16, 2005.
- Moore MJ, Goldstein D, Hamm J, et al. Erlotinib plus gemcitabine compared to gemcitabine alone in patients with advanced pancreatic cancer. A phase III trial of the National Cancer Institute of Canada Clinical Trials Group [NCIC-CTG]. J Clin Oncol (Meeting Abstracts) 2005;23:1.
