A few patients with stage IIB pancreatic cancer have tumors that are technically resectable, but few cures have been reported. More frequently, palliative bypass of biliary obstruction by surgical, endoscopic, or radiologic means should be performed.[1]

While there are data demonstrating a survival advantage associated with combined chemotherapy and radiation therapy,[2] most patients with unresectable pancreatic cancer should be considered for participation in clinical trials. Radiation therapy alone may palliate symptoms, but a survival benefit is not demonstrable.

Pain associated with unresectable pancreatic cancer may be palliated with radiation therapy, with or without chemotherapy,[2-5] or with chemical splanchnicectomy with 50% alcohol at the time of surgical exploration.[6] Celiac nerve blocks and local neurosurgical procedures to relieve pain can be considered.[7]

Standard treatment options:

1. Pancreatectomy when feasible, with or without adjuvant fluorouracil (5-FU) chemotherapy and radiation therapy.[6,8-11]
2. Radiation therapy with 5-FU chemotherapy for patients with locally unresectable disease.[2-4]
3. Palliative surgical biliary and/or gastric bypass, percutaneous radiologic biliary stent placement, or endoscopic biliary stent placement.[12,13]

Treatment options under clinical evaluation:

1. For patients with resected tumors, postoperative radiation therapy with other chemotherapeutic agents. In 2002, the Radiation Therapy Oncology Group completed a prospective, multicenter randomized trial to evaluate whether gemcitabine chemotherapy administered prior to and following radiation with concurrent 5-FU is superior to adjuvant 5-FU for patients with completely resected tumors; preliminary analysis is pending.[14]
2. Postoperative chemotherapy alone. The ESPAC-3 trial is ongoing to evaluate postoperative chemotherapy with either 5-FU/leucovorin or gemcitabine versus no additional treatment.[15]
3. Postoperative biologic agents including farnesyl transferase inhibitors and avastin in combination with radiation and/or chemotherapy.
4. For patients with locally unresectable tumors, preoperative irradiation with various chemotherapeutic agents and/or radiosensitizers is under clinical evaluation.
5. Intraoperative radiation therapy and/or implantation of radioactive sources.[5,16]

Information about ongoing clinical trials is available from the NCI Cancer.gov Web site.

References

1. Sohn TA, Lillemoe KD, Cameron JL, et al.: Surgical palliation of unresectable periampullary adenocarcinoma in the 1990s. J Am Coll Surg 188 (6): 658-66; discussion 666-9, 1999.  [PUBMED Abstract]
   
   
2. Moertel CG, Frytak S, Hahn RG, et al.: Therapy of locally unresectable pancreatic carcinoma: a randomized comparison of high dose (6000 rads) radiation alone, moderate dose radiation (4000 rads + 5-fluorouracil), and high dose radiation + 5-fluorouracil: The Gastrointestinal Tumor Study Group. Cancer 48 (8): 1705-10, 1981.  [PUBMED Abstract]
   
   
3. Whittington R, Solin L, Mohiuddin M, et al.: Multimodality therapy of localized unresectable pancreatic adenocarcinoma. Cancer 54 (9): 1991-8, 1984.  [PUBMED Abstract]
   
   
4. Moertel CG, Childs DS Jr, Reitemeier RJ, et al.: Combined 5-fluorouracil and supervoltage radiation therapy of locally unresectable gastrointestinal cancer. Lancet 2 (7626): 865-7, 1969.  [PUBMED Abstract]
   
   
5. Tepper JE, Noyes D, Krall JM, et al.: Intraoperative radiation therapy of pancreatic carcinoma: a report of RTOG-8505. Radiation Therapy Oncology Group. Int J Radiat Oncol Biol Phys 21 (5): 1145-9, 1991.  [PUBMED Abstract]
   
   
6. Kalser MH, Ellenberg SS: Pancreatic cancer. Adjuvant combined radiation and chemotherapy following curative resection. Arch Surg 120 (8): 899-903, 1985.  [PUBMED Abstract]
   
   
7. Polati E, Finco G, Gottin L, et al.: Prospective randomized double-blind trial of neurolytic coeliac plexus block in patients with pancreatic cancer. Br J Surg 85 (2): 199-201, 1998.  [PUBMED Abstract]
   
   
8. Further evidence of effective adjuvant combined radiation and chemotherapy following curative resection of pancreatic cancer. Gastrointestinal Tumor Study Group. Cancer 59 (12): 2006-10, 1987.  [PUBMED Abstract]
   
   
9. Klinkenbijl JH, Jeekel J, Sahmoud T, et al.: Adjuvant radiotherapy and 5-fluorouracil after curative resection of cancer of the pancreas and periampullary region: phase III trial of the EORTC gastrointestinal tract cancer cooperative group. Ann Surg 230 (6): 776-82; discussion 782-4, 1999.  [PUBMED Abstract]
   
   
10. Neoptolemos JP, Dunn JA, Stocken DD, et al.: Adjuvant chemoradiotherapy and chemotherapy in resectable pancreatic cancer: a randomised controlled trial. Lancet 358 (9293): 1576-85, 2001.  [PUBMED Abstract]
    
    
11. Neoptolemos JP, Stocken DD, Friess H, et al.: A randomized trial of chemoradiotherapy and chemotherapy after resection of pancreatic cancer. N Engl J Med 350 (12): 1200-10, 2004.  [PUBMED Abstract]
    
    
12. van den Bosch RP, van der Schelling GP, Klinkenbijl JH, et al.: Guidelines for the application of surgery and endoprostheses in the palliation of obstructive jaundice in advanced cancer of the pancreas. Ann Surg 219 (1): 18-24, 1994.  [PUBMED Abstract]
    
    
13. Baron TH: Expandable metal stents for the treatment of cancerous obstruction of the gastrointestinal tract. N Engl J Med 344 (22): 1681-7, 2001.  [PUBMED Abstract]
    
    
14. Regine WF, Radiation Therapy Oncology Group: Phase III Randomized Study of Adjuvant Fluorouracil-Based Chemoradiotherapy Preceded and Followed By Fluorouracil Versus Gemcitabine in Patients With Resected Adenocarcinoma of the Pancreas, RTOG-9704, Clinical trial, Closed.  [PDQ Clinical Trial]
    
    
15. ESPAC-3(v2) Phase III Adjuvant Trial in Pancreatic Cancer Comparing 5FU and D-L-Folinic Acid vs. Gemcitabine. Leeds, UK: National Cancer Research Network Trials Portfolio, 2004. Available online. Last accessed June 7, 2004. 
    
    
16. Reni M, Panucci MG, Ferreri AJ, et al.: Effect on local control and survival of electron beam intraoperative irradiation for resectable pancreatic adenocarcinoma. Int J Radiat Oncol Biol Phys 50 (3): 651-8, 2001.  [PUBMED Abstract]
    
    

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