Intrahepatic interleukin-2 with chemotherapy for unresectable liver metastases: a randomized multicenter trial.
OBJECTIVE
A pilot study of Interleukin-2 (IL-2) with chemotherapy for unresectable colorectal liver metastases revealed a favorable response rate (76%). This prospective, randomized, multicenter study was conducted to evaluate the efficacy of this treatment protocol.


METHODS
Over a period of 32 months, 46 patients with unresectable liver metastases were randomly assigned to 1 of 3 treatment groups: group A: chemotherapy alone, group B: chemotherapy plus high-dose, intermittent IL-2 (2.1 x 10(6) U twice weekly) or group C: chemotherapy plus low-dose, continuous IL-2 (7 x 10(5) U daily). Treatment continued for 4 weeks in the hospital and on an outpatient basis according to the clinical response. No crossover between treatment arms was permitted.


RESULTS
IL-2 combined with chemotherapy produced a higher complete and partial response rate of 40% in group A, 60% in group B, and 78% in group C. Toxicity related to IL-2 included fever, chills, malaise, and eosinophilia.


CONCLUSIONS
Hepatic arterial infusion of chemotherapy plus IL-2 resulted in an increased tumor response when compared with chemotherapy alone. To confirm the efficacy of this treatment protocol, we have started a large-scale, randomized, multi-institution trial.
Okuno
K
K
First Department of Surgery, Kinki University School of Medicine, Osaka-sayama, Japan.
Yasutomi
M
M
Kon
M
M
Hatakeyama
K
K
Muto
T
T
Kitajima
M
M
Koyanagi
Y
Y
Hamano
K
K
Ohta
H
H
Aiba
K
K
Arai
Y
Y
Sowa
M
M
Kikkawa
N
N
Takayasu
Y
Y
Isomoto
H
H
D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D003131:Combined Modality Therapy; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage / Q000009:adverse effects; D006801:Humans; D007376:Interleukin-2 / Q000008:administration & dosage*; D008113:Liver Neoplasms / Q000188:drug therapy / Q000556:secondary*; D008297:Male; D008875:Middle Aged; D016685:Mitomycin / Q000008:administration & dosage / Q000009:adverse effects; D010166:Palliative Care; D010865:Pilot Projects; D011446:Prospective Studies; D016896:Treatment Outcome
D007376:Interleukin-2; D016685:Mitomycin; D005472:Fluorouracil