For patients with localized pancreatic adenocarcinoma, the combination
of radiation therapy and 5-fluorouracil has been shown to enhance pat
ient 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 r
adiation therapy, as noted in the original randomized study of the Gas
trointestinal Tumor Study Group. When the disease is locally unresecta
ble, 60 Gy of radiation administered in a double split regimen, in com
bination with 5-fluorouracil, has significantly prolonged survival. Sp
lit courses of radiation therapy seem better tolerated, allowing a gre
ater proportion of patients to complete this phase of treatment. Hyper
fractionation, heavy ion irradiation and intraoperative radiation ther
apy have not been found to be more beneficial. Newer approaches includ
e continuous intravenous or intraarterial infusion of the 5-fluorourac
il, addition of mitomycin C or cisplatin. The results of neoadjuvant t
rials of radiation and chemotherapy are not sufficiently mature to det
ermine their effect on patient survival. Neoadjuvant therapy has not b
een subjected to testing in randomized trials. Chemotherapy will conti
nue to offer very limited benefit for patients with advanced metastati
c disease until more effective drugs can be developed. Innovative appr
oaches utilizing growth factors and photodynamic therapy should be stu
died in carefully monitored fashion.