The antitumor effects produced by combinations of
cisplatin (Pt), substituted dithiocarbamates (
dimethyldithiocarbamate [DmDTC] and
sodium N-methyl-D-glucamine dithiocarbamate [NMGDTC]) and
hyperthermia (H) were measured and compared to those produced by single agents alone in C3H/HeN mice bearing the transplantable radiation-induced
fibrosarcoma, RIF-1, in one or both hind feet. The average
tumor volumes of control and treatment groups were compared periodically
after treatment with H. Combinations of H and Pt completely resolved established foot
tumors in 10/13 mice. However, evidence of long-term nephrotoxicity and gastrointestinal (GI) toxicity became evident causing death of these mice within 120 to 122 days after
tumor inoculation.
Hyperthermia plus DmDTC resolved
tumors in heated and non-heated feet in 3/8 mice, thus demonstrating both ipsilateral and contralateral anti-
tumor activity. Furthermore, H-Pt-NMGDTC produced complete
tumor resolution in 7/13 mice; these mice survived and were
tumor-free 180 days post inoculation and autopsies revealed no appreciable nephro- or GI toxicity. In addition, 4/8 mice underwent complete
tumor resolution in heated left feet plus dramatic retarding of
tumor growth in unheated right feet (ipsilateral and contralateral anti-
tumor effects). Five heat-treated left foot
tumors resolved in the H-Pt-DmDTC group with one mouse demonstrating resolution of
tumor in both feet. Advanced foot
tumors were treated with H-DmDTC and H-Pt-DmDTC.
Hyperthermia and Pt were administered on day 0 of the experiment and DmDTC on days 0 through 3; dramatic
tumor shrinkage continued through day 6 for a total of 75 to 80 percent reduction of
tumor volume in both groups. The concurrent administration of DmDTC or NMGDTC with H and Pt prevented or greatly reduced nephrotoxicity and GI toxicity in all experiments without retarding anti-
tumor efficacy.