Phase III study of interferon alfa-NL as adjuvant treatment for resectable renal cell carcinoma: an Eastern Cooperative Oncology Group/Intergroup trial.
OBJECTIVE
To evaluate the role of adjuvant interferon alfa after complete resection of locally extensive renal cell carcinoma.


METHODS
A total of 283 eligible patients with pT3-4a and/or node-positive disease were randomly assigned after radical nephrectomy and lymphadenectomy to observation or to interferon alfa-NL (Wellferon, Burroughs-Wellcome, Research Park, NC) given daily for 5 days every 3 weeks for up to 12 cycles. Patients were stratified on the basis of pathologic stage. Patients remained on treatment until documented recurrence, excessive toxicity, or patient/physician preference deemed removal appropriate.


RESULTS
At median follow-up of 10.4 years, median survival was 7.4 years in the observation arm and 5.1 year in the treatment arm (log-rank P =.09). Median recurrence-free survival was 3.0 years in the observation arm and 2.2 years in the interferon arm (P =.33). Performance status (P =.003), nodal status (N2 v N0, P <.0001), and tumor stage (P =.0002) were significant prognostic factors in multivariate analysis. A proportional hazards model examining the effects of treatment arm and time to recurrence on survival after recurrence among patients who recurred found that random assignment to interferon treatment (P =.009) and shorter time to recurrence (P <.0001) were independent predictors of shorter survival after recurrence. Although no lethal toxicities were observed, severe (grade 4) toxicities including neutropenia, myalgia, fatigue, depression, and other neurologic toxicities occurred in 11.4% of those randomly assigned to interferon treatment.


CONCLUSIONS
Adjuvant treatment with interferon did not contribute to survival or relapse-free survival in this group of patients.
Messing
Edward M
EM
University of Rochester School of Medicine and Dentistry, Rochester, NY 14642, USA. edward_messing@urmc.rochester.edu
Manola
Judith
J
Wilding
George
G
Propert
Kathleen
K
Fleischmann
Jonathan
J
Crawford
E David
ED
Pontes
J Edson
JE
Hahn
Richard
R
Trump
Donald
D
D000328:Adult; D000368:Aged; D002292:Carcinoma, Renal Cell / Q000401:mortality / Q000628:therapy*; D017024:Chemotherapy, Adjuvant; D003131:Combined Modality Therapy; D018572:Disease-Free Survival; D004334:Drug Administration Schedule; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D016898:Interferon-alpha / Q000008:administration & dosage / Q000627:therapeutic use*; D007680:Kidney Neoplasms / Q000401:mortality / Q000628:therapy*; D008197:Lymph Node Excision; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local; D009392:Nephrectomy; D011379:Prognosis; D015996:Survival Rate; D016896:Treatment Outcome
D016898:Interferon-alpha