A Phase IA Trial of Sequential Administration Recombinant DNA-Produced Interferons: Combination Recombinant Interferon Gamma and Recombinant Interferon Alfa in Patients with Metastatic Renal Cell Carcinoma.
Publication/Presentation Date
10-1-1990
Abstract
This study investigated the effects of sequentially administered recombinant interferon gamma (rIFN gamma) and recombinant interferon alfa (rIFN alpha) in 36 patients with metastatic renal cell carcinoma (RCC). rIFN alpha was subcutaneously administered daily for 70 days at dosages that varied (2.5, 5, 10, and 20 x 10(6) U/m2) across four cohorts of patients. Within each cohort of patients receiving a given dose of rIFN alpha, three subsets of patients received either 30, 300, or 1,000 micrograms/m2 rIFN gamma. rIFN gamma was administered intravenously for 5 days every third week, 6 hours prior to administration of rIFN alpha. Dose-limiting toxicity (DLT) included constitutional symptoms, leukopenia, nephrotic syndrome with acute renal failure, hypotension associated with death, and congestive heart failure. DLT was related more often to the rIFN alpha dose level than to rIFN gamma dose level. Maximum-tolerated dose (MTD) was 10 x 10(6) U/m2 rIFN alpha and 1,000 micrograms/m2 rIFN gamma. Six patients failed to complete a minimum of 21 days of therapy due to toxicity or rapid progression of disease. Clinical responses were seen in eight of 30 assessable patients. Two patients experienced complete remission and have remained in complete remission 20+ and 22+ months. An additional six patients have shown partial responses for 4 to 18+ months. One patient in partial remission continues to show slow regression of pulmonary and liver lesions off therapy with rIFNs. Clinical responses have remained durable for patients with complete remissions and patients with partial remissions. The results of this study suggest that toxicities associated with combination rIFN therapy can be reduced by administering these agents sequentially as opposed to simultaneously.
Volume
8
Issue
10
First Page
1637
Last Page
1649
ISSN
0732-183X
Published In/Presented At
Ernstoff, M. S., Nair, S., Bahnson, R. R., Miketic, L. M., Banner, B., Gooding, W., & ... Kirkwood, J. M. (1990). A phase IA trial of sequential administration recombinant DNA-produced interferons: combination recombinant interferon gamma and recombinant interferon alfa in patients with metastatic renal cell carcinoma. Journal Of Clinical Oncology: Official Journal Of The American Society Of Clinical Oncology, 8(10), 1637-1649.
Disciplines
Medical Sciences | Medicine and Health Sciences
PubMedID
2120392
LVHN link
http://search.ebscohost.com/login.aspx?direct=true&db=mnh&AN=2120392&site=ehost-live&scope=site
Peer Reviewed for front end display
Peer-Reviewed
Department(s)
Department of Medicine, Hematology-Medical Oncology Division, Department of Medicine Faculty
Document Type
Article