Method of Prolonging Cancerous Patient Survival in Humans With Hydrazine Sulfate

The dosages of hydrazine sulfate employed in the present invention can vary from 1 to 5 mg/kg daily, which is well below the LD50 and has been found to be well tolerated in the majority of early-stage patients so treated for periods of up to four years.

Preferably, the regimen followed is one 60 mg capsule of hydrazine sulfate daily for the first three days, then two such capsules daily for the next three days, and then three 60 mg capsules each day thereafter. In actual practice, patients weighing over 130 pounds do well on three or four 60 mg capsules daily. For patients weighing less than 100 pounds, the regimen followed is preferably one 30 mg capsule of hydrazine sulfate daily for the first three days, then two such capsules daily for the next three days, and then two or three 30 mg capsules each day thereafter. For best results blood levels of hydrazine sulfate should be determined on these patients in order to establish a most effective non-toxic dose.

Hydrazine sulfate therapy can advantageously be combined with other modalities for cancer treatment like chemotherapy, immunotherapy, radiation and surgery.

Hydrazine sulfate is most effective when administered usually by itself one or two hours before meals in the form of a gelatin capsule. If desired, the sulfate can be dissolved or suspended in sterile, aqueous, isotonic saline solution and given orally and parenterally. Likewise, hydrazine sulfate can be formulated with solid carriers such as talc, corn starch or stearic acid and compressed into tablets for oral administration. Such tablets can be enteric coated with shellac or cellulose acetate phthalate in a manner well known to those skilled in the pharmaceutical art.

The efficacy of hydrazine sulfate in prelonging survival in early-stage human cancer patients has now been demonstrated for the first time in a placebo-controlled, double-blind experiment with a statistically significant number of subjects.

Early-stage human cancer patients are distinguished from late-stage human cancer patients on the basis of the nature of their symptoms. These symptoms have been quantitatively correlated by two recognized methods of categorization: the Eastern Cooperative Oncology Group (ECOG) Performance Status Score (also known as Zubrod's ) and the Karnofsky Rating Scale. The relationship between these two methods and the resulting division of human cancer patients into early-stage and late-stage, as recognized by ECOG and Karnofsky rating criteria, is set forth as follows:

In the placebo-controlled, double-blind experiemnt referred to above, to determine whether hydrazine sulfate treatment is associated with a survival benefit (R.T. Chlebowski et al., "Influence of Hydrazine Sulfate on Survival in Non-Small Cell Lung Cancer: A Randomized Placebo-Controlled Trial", presented at the Annual Meeting of the American Society for Clinical Oncology, May 17-19, 1987, Atlanta, Georgia), sixty-five patients with unresectable, non-small cell lung cancer and no prior chemotherapy were randomized to receive combination chemotherapy with either hydrazine sulfate or placebo addition for a period of up to four years. All received Platinol/Velban/Blenoxane (PVB) chemotherapy every 28 days, consisting of Platinol 100 mg/m.sup.2 ; Velban 4 mg/m.sup.2, days 1 and 2; and Blenoxane 10 units every 8 hours for three doses. After the initial three cycles, the Blenoxane was discontinued and the Platinol dose was reduced to 50 mg/m.sup.2.

Pre-chemotherapy factors including age, sex, performance status (PS), prior weight loss and disease extent were comparable in the two groups, with pre-chemotherapy performance status (0-vs. 2) and prior weight loss (>10%) subsequently influencing overall survival (p<0.05). Toxicity was that expected from PVB with three patients not continuing hydrazine sulfate because of additional nausea. Survival by hydrazine sulfate or placebo were:

Specifically, this increased survival time occurred in early-stage human cancer patients with Performance Status 0 or 1 (PS 0-1), whereas late-stage patients (PS 2) did not exhibit prolonged survival.

Several patients with tumors of the prostate, lung, breast, ovary, lymph, cervix, thyroid, pancreas and other tumor sites were treated with hydrazine sulfate according to the preferred regimen previously set forth.