Controlled clinical trial of interferon-gamma as postoperative surgical adjuvant therapy for colon cancer.
OBJECTIVE
The primary goal of this study was to assess the effectiveness of interferon gamma (IFN-gamma) to prevent tumor relapse following potentially curative surgery in patients with high-risk colon cancer. A secondary goal was to determine the effect of IFN-gamma on immune function and to correlate alterations in immune parameters with survival.


METHODS
Three to 4 weeks after undergoing resection of all known malignant disease, 99 patients with stage II, III, or IV colon cancer were randomly assigned to receive IFN-gamma 0.2 mg total dose by subcutaneous injection daily for 6 months or observation. Serial assessment of human leukocyte antigen (HLA)-DR expression and Fc receptors on peripheral-blood monocytes was conducted in 24 patients who received IFN-gamma and 27 control patients.


RESULTS
With a median follow-up duration of 59 months in patients still alive, there was evidence of a detrimental effect on time to relapse (P = .03) among patients who received IFN-gamma. There was no significant difference in patient survival (P = .12). This study has sufficient power to rule out a 25% reduction in death rate for patients who received IFN-gamma (P < .05). Significant enhancement of immune function was observed in patients treated with IFN-gamma as measured by HLA-DR expression (P < .01) and Fc receptors (P < .001) on peripheral-blood monocytes.


CONCLUSIONS
This study effectively rules out any clinically meaningful benefit for IFN-gamma as surgical adjuvant treatment for patients with high-risk colon cancer. Although significant enhancement of nonspecific immune function was seen with this dosage administration schedule of IFN-gamma, this was not associated with any demonstrable antitumor effect.
Wiesenfeld
M
M
Cedar Rapids Oncology Project Community Clinical Oncology Program, IA, USA.
O'Connell
M J
MJ
Wieand
H S
HS
Gonchoroff
N J
NJ
Donohue
J H
JH
Fitzgibbons
R J
RJ
Krook
J E
JE
Mailliard
J A
JA
Gerstner
J B
JB
Pazdur
R
R
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D003110:Colonic Neoplasms / Q000276:immunology / Q000601:surgery / Q000628:therapy*; D003131:Combined Modality Therapy; D005260:Female; D005500:Follow-Up Studies; D006684:HLA-DR Antigens / Q000378:metabolism; D006801:Humans; D007371:Interferon-gamma / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D009000:Monocytes / Q000378:metabolism; D015999:Multivariate Analysis; D009364:Neoplasm Recurrence, Local / Q000517:prevention & control; D011182:Postoperative Care; D016016:Proportional Hazards Models; D011446:Prospective Studies; D011961:Receptors, Fc / Q000378:metabolism; D012044:Regression Analysis
D006684:HLA-DR Antigens; D011961:Receptors, Fc; D007371:Interferon-gamma