Antitumor activity of interleukin-1 alpha and cisplatin in a murine model system.
BACKGROUND
Interleukin-1 alpha (IL-1 alpha) has potent antitumor activity either alone or combined with alkylating agents such as cisplatin and mitomycin C or porfiromycin. Cisplatin is an effective chemotherapeutic agent in the treatment of advanced squamous cell carcinoma of the head and neck (SCCHN). In the murine SCCVII/SF squamous cell carcinoma tumor model, IL-1 alpha induced acute hemorrhagic necrosis and increased clonogenic cell kill.


OBJECTIVE
To determine the efficacy of cisplatin and IL-1 alpha, singly and in combination, in the treatment of SCCHN.


METHODS
Syngeneic C3H/HeN mice were treated with single-dose, concurrent, intraperitoneal injections of cisplatin and interleukin-1 alpha 14 days after subcutaneous tumor implantation and were monitored for delayed tumor regrowth.


RESULTS
Cisplatin alone, but not IL-1 alpha, induced significant delayed tumor regrowth when compared with control. The combination of IL-1 alpha and cisplatin was even more effective in delaying tumor regrowth than cisplatin alone. Fractional tumor volume was significantly reduced in animals treated with the combination of cisplatin and IL-1 alpha compared with those treated with IL-1 alpha alone.


CONCLUSIONS
Results of interleukin-1 alpha and cisplatin dose-response experiments reveal that the combination of low-dose cisplatin and interleukin-1 alpha is more effective than high-dose cisplatin alone. Our data suggest that cisplatin and IL-1 alpha may be efficacious in the treatment of SCCHN.
Grandis
J R
JR
Department of Otolaryngology, University of Pittsburgh School of Medicine, Pa.
Chang
M J
MJ
Yu
W D
WD
Johnson
C S
CS
D000818:Animals; D002294:Carcinoma, Squamous Cell / Q000473:pathology / Q000628:therapy*; D002945:Cisplatin / Q000627:therapeutic use*; D005260:Female; D006470:Hemorrhage / Q000209:etiology; D007375:Interleukin-1 / Q000009:adverse effects / Q000627:therapeutic use*; D051379:Mice; D008809:Mice, Inbred C3H; D014407:Tumor Cells, Cultured
D007375:Interleukin-1; D002945:Cisplatin