DNA base adducts in urine andwhite blood cells of cancer patients receiving combination chemotherapies which include N-methyl-N-nitrosourea.

Abstract 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.

Nitrosourea derivatives for the treatment of Hodgkin's disease involving the central nervous system: a study of 23 cases.

This study deals with the effectiveness of nitrosourea derivatives (nitrosomethylurea and CCNU) used as single agents or in combination with vinca alkaloids, procarbazine and prednisolone in 23 patients suffering from Hodgkin's disease with spinal cord or intracranial involvement. Complete regression of neurologic symptoms was observed in 61% of patients with spinal cord compression and in 4 out of 5 cases of brain involvement. No relationship was found between type, degree and duration of symptoms, and treatment efficacy.

[Use of nitrosourea derivatives in the treatment of patients with Hodgkin's disease with lesions of the central nervous system]. / Primenenie proizvodnykh nitrozomocheviny v lechenii bol'nykh limfogranulematozom s porazheniem tsentral'noi nervnoi sistemy.

The study deals with the effectiveness of nitrosourea derivatives (nitrosomethylurea and CCNU) used for monochemotherapy or polychemotherapy in combination with vinca alkaloids, natulan and prednisolone in 22 patients suffering Hodgkin's disease with spinal cord and intracranial involvement. Complete regression of neurologic symptoms was seen in 61.1% of patients with spinal cord dysfunction and in 3 of 4 cases of brain involvement. The effectiveness of nitrosomethylurea-based regimens did not differ-significantly from those including CCNU. The longest complete remission obtained was 124+ months. No relationship was found between the type, degree and duration of symptoms, on the one hand, and the likelihood of achieving complete remission, on the other.