In other experiments, hydrazine sulfate was combined with individual chemotherapy drugs (cyclophosphamide, mitomycin C, methotrexate, bleomycin, fluorouracil [5-FU], carmustine [BCNU], or neocarzinostatin) to treat Walker 256 carcinosarcoma tumors in rats and solid L-1210 leukemia tumors in mice.[13,14,15] For both tumor types, enhanced anticancer effects were observed. In the experiments with L-1210 tumors, cyclophosphamide and mitomycin C were more effective when combined with hydrazine sulfate than they were when used alone. As indicated previously, hydrazine sulfate alone had no effect against solid L-1210 tumors.
Addition of the drug clofibrate to the hydrazine sulfate plus chemotherapy drug combinations was reported to produce even greater antitumor effects. Clofibrate lowers blood lipid levels and has the potential to inhibit gluconeogenesis by limiting the availability of lipid breakdown products for the synthesis of glucose. This three drug treatment regimen, however, was tested against only one type of tumor (Walker 256 carcinosarcomas in rats).
Hydrazine sulfate has also been tested in combination with drugs that affect the uptake of glucose by cells. The combination of hydrazine sulfate and phloretin, a drug that blocks glucose uptake, showed greater activity against FBCa bladder cancer tumors in rats than was found with hydrazine sulfate alone; however, this combination did not exhibit enhanced antitumor activity against 13762NF mammary adenocarcinomas in rats. When hydrazine sulfate was combined with the drug phloridzin, which is similar to phloretin, using the same two tumor models, no increase in anticancer activity was observed. When hydrazine sulfate was combined with the drug phenformin, which increases glucose uptake by cells (and lowers blood glucose levels), enhanced antitumor activity against Walker 256 carcinosarcomas in rats was observed.
In the 1980s, the National Cancer Institute (NCI) conducted preclinical studies of hydrazine sulfate as a single agent, using many of the animal tumor models described above. With the exception of borderline activity against Walker 256 carcinosarcomas in rats, no evidence of antitumor activity was found. In view of these results, NCI recommended against further evaluation of hydrazine sulfate as an anticancer agent. However, clinical investigation of this compound continued, largely because of its potential as a treatment for cancer-related anorexia and cachexia.
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