Adjuvant intra-arterial chemotherapy and radiotherapy versus surgery alone in resectable pancreatic and periampullary cancer: a prospective randomized controlled trial.
BACKGROUND
Success of surgical treatment for pancreatic and periampullary cancer is often limited due to locoregional recurrence and/or the development of distant metastases.


OBJECTIVE
The survival benefit of celiac axis infusion (CAI) and radiotherapy (RT) versus observation after resection of pancreatic or periampullary cancer was investigated.


METHODS
In a randomized controlled trial, 120 consecutive patients with histopathologically proven pancreatic or periampullary cancer received either adjuvant treatment consisting of intra-arterial mitoxantrone, 5-FU, leucovorin, and cisplatinum in combination with 30 x 1.8 Gy radiotherapy (group A) or no adjuvant treatment (group B). Groups were stratified for tumor type (pancreatic vs. periampullary tumors).


RESULTS
After surgery, 120 patients were randomized (59 patients in the treatment group, 61 in the observation group). The median follow-up was 17 months. No significant overall survival benefit was seen (median, 19 vs. 18 months resp.). Progressive disease was seen in 86 patients: in 37 patients in the CAI/RT group, and in 49 patients in the observation group (log-rank P < 0.02). Subgroup analysis showed significantly less liver metastases after adjuvant treatment in periampullary tumors (log-rank P < 0.03) without effect on local recurrence. Nonetheless, there was no significant effect on overall survival in these patients (log-rank P = 0.15). In patients with pancreatic cancer, CAI/RT had no significant effect on local recurrence (log-rank P = 0.12) neither on the development of liver metastases (log-rank P = 0.76) and consequently, no effect on overall survival.


CONCLUSIONS
This adjuvant treatment schedule results in a prolonged time to progression. For periampullary tumors, CAI/RT induced a significant reduction in the development of liver metastases, with a possible effect on overall survival. Especially in these tumors, CAI/RT might prove beneficial in larger groups and further research is warranted.
Morak
Marjolein J M
MJ
Department of Surgery, Erasmus MC Rotterdam, Rotterdam, The Netherlands.
van der Gaast
Ate
A
Incrocci
Luca
L
van Dekken
Herman
H
Hermans
John J
JJ
Jeekel
Johannes
J
Hop
Wim C J
WC
Kazemier
Geert
G
van Eijck
Casper H J
CH
D000230:Adenocarcinoma / Q000188:drug therapy / Q000401:mortality* / Q000532:radiotherapy / Q000601:surgery / Q000628:therapy*; D000328:Adult; D000368:Aged; D014670:Ampulla of Vater; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D017024:Chemotherapy, Adjuvant; D003138:Common Bile Duct Neoplasms / Q000188:drug therapy / Q000401:mortality* / Q000532:radiotherapy / Q000601:surgery* / Q000628:therapy*; D003515:Cycloleucine / Q000008:administration & dosage / Q000031:analogs & derivatives; D018450:Disease Progression; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage*; D006801:Humans; D007261:Infusions, Intra-Arterial; D007854:Lead; D008297:Male; D008875:Middle Aged; D008942:Mitoxantrone / Q000008:administration & dosage*; D010190:Pancreatic Neoplasms / Q000188:drug therapy / Q000401:mortality* / Q000532:radiotherapy / Q000601:surgery / Q000628:therapy*; D011379:Prognosis; D011446:Prospective Studies; D018714:Radiotherapy, Adjuvant; D013440:Sulfides; D016896:Treatment Outcome
D013440:Sulfides; D003515:Cycloleucine; C018391:lead sulfide; D007854:Lead; C065594:cispentacin; D008942:Mitoxantrone; D005472:Fluorouracil