Current approaches to multimodality management of advanced pancreatic cancer

For patients with localized pancreatic adenocarcinoma, the combination of radiation therapy and 5-fluorouracil has been shown to enhance patient survival. Following pancreatectomy, results in a second group of patients confirmed the benefit of 40 Gy of radiation administered as a split course, combined with 5-fluorouracil during and following the radiation therapy, as noted in the original randomized study of the Gastrointestinal Tumor Study Group. When the disease is locally unresectable, 60 Gy of radiation administered in a double split regimen, in combination with 5-fluorouracil, has significantly prolonged survival. Split courses of radiation therapy seem better tolerated, allowing a greater proportion of patients to complete this phase of treatment. Hyperfractionation, heavy ion irradiation and intraoperative radiation therapy have not been found to be more beneficial. Newer approaches include continuous intravenous or intraarterial infusion of the 5-fluorouracil, addition of mitomycin C or cisplatin. The results of neoadjuvant trials of radiation and chemotherapy are not sufficiently mature to determine their effect on patient survival. Neoadjuvant therapy has not been subjected to testing in randomized trials. Chemotherapy will continue to offer very limited benefit for patients with advanced metastatic disease until more effective drugs can be developed. Innovative approaches utilizing growth factors and photodynamic therapy should be studied in carefully monitored fashion.