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Urinary 3-methyladenine (3-MeAde) excretion andlymphocyte DNA adduct formation was studied in 15 patients receiving methylnitrosourea (MNU) at several dose levels (250 mg, 300 mg and600 mg total dose, 143-385 mg m(-2)) as part of various combination chemotherapies for advanced tumours (malignant melanoma, lymphoblastic lymphosarcorna andHodgkin's disease). Urinary 3-MeAde levels were significantly increased over background in patients at all dose levels (p < 0.001) andthe increases were dose-dependent (r = 0.77, p < 0.01). There were large interindividual variations in the excretion of 3-MeAde at each dose of MNU. In a subset of patients, N7-methyl-2-deoxyguanosine (7-MedG) andO(6)-methyl-2'-deoxyguanosine (O(6)-WedG) levels in DNA from blood leucocytes showed dose-dependent increases, however there were no simple relationships between urinary methylated DNA bases andleucocyte DNA adducts. Levels of adducts in leucocyte DNA (7-MedG, < 17-217 μmol mol(-1) dG; O(6)-WedG, < 1.6-35 μmol mol(-1) dG) were comparable with those reported for other methylating chemotherapeutic drugs. Leucocyte DNA andurinary methyl adducts may be useful markers of individual responses to treatment with methylating drugs.

The results of Sehydrin (Hydrazine Sulfate, HS) treatment of 740 patients with the advanced, recurrent or metastatic solid tumours of various localizations or malignant lymphomas, for whom all the methods of specific treatment (surgery, radiation, chemotherapy) had been exhausted are presented in this work. The objective response, symptomatic therapeutic effects and toxicity were estimated. Clinically significant objective responses were registered in patients with the soft tissue sarcomas, including neuroblastomas, and paradoxically--in such semimalignant tumours as desmoids. Although the objective response in patients with the lung cancer (90%--non-small cell) was only 4%, stabilization of long duration was registered in 22% of cases connected with the impressive relief of heavy common symptoms in 38.5% of the treated patients. Such a subjective response was established in 46.6% of all the 740 cases. The drug given per os was well tolerated by patients in primary and subsequent courses and did not induce myelosuppression or other significant side effects. On the basis of observations available, Sehydrin may be assessed as an alternative drug for the treatment and symptomatic therapy of patients with some advanced solid tumours and malignant lymphomas at a disease stage when the other methods of treatment can not be used. A possible mechanism of antitumour and symptomatic action is being discussed.

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