Evaluation of combinations of interferons and cytotoxic drugs in murine tumor models in vivo.
This investigation was conducted to provide preclinical in vivo tumor response data collected under standardized conditions with a range of clinically useful drugs combined with type I (alpha/beta) or type II (gamma) interferon. Murine tumor models used were P388 leukemia, Meth A sarcoma, and B16 melanoma. Eleven cytotoxic drugs were studied. Interferon combinations with cytosine arabinoside provided consistent indications of activity greater than that of the respective single agents. Doxorubicin and cisplatin each prolonged the time to treatment failure, relative to single-agent results, when they were combined with gamma-interferon in the Meth A and B16 models. Interferon combinations with methotrexate, 6-mercaptopurine, 6-thioguanine, ampligen, suramin, 5-fluorouracil, cyclophosphamide, and vinblastine yielded no evidence of any positive therapeutic interactions under the conditions of this study.
Harrison
S D
SD
Chemotherapy and Toxicology Research Department, Southern Research Institute, Birmingham, Alabama 35255-5305.
Stevens
J J
JJ
Waud
W R
WR
Dykes
D J
DJ
Schmid
S M
SM
Griswold
D P
DP
D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D002945:Cisplatin / Q000008:administration & dosage; D003561:Cytarabine / Q000008:administration & dosage; D004317:Doxorubicin / Q000008:administration & dosage; D004354:Drug Screening Assays, Antitumor; D005260:Female; D007370:Interferon Type I / Q000008:administration & dosage; D007371:Interferon-gamma / Q000008:administration & dosage; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA; D009374:Neoplasms, Experimental / Q000188:drug therapy*
D000970:Antineoplastic Agents; D007370:Interferon Type I; D003561:Cytarabine; D004317:Doxorubicin; D007371:Interferon-gamma; D002945:Cisplatin