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The local and resorption action of 50% prospidin ointment administered at doses up to 100 mg/kg for a long time was studied in rabbit experiments. Prospidin ointment was established to exert no resorption action in doses tested. At the site of the ointment application there occur skin necrotic changes. Complete regeneration of the epithelium with hair recovery is recorded 2 months after the drug is discontinued.
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A comparative assay of cytostatic combinations was carried out in a number of transplantable mouse tumors: L1210, Lewis lung carcinoma, Sarcoma 180 and others. The results suggest that the combination cyclophosphamide (CPH) plus procarbazine (PROC) enhances the antitumoral activity in comparison with monochemotherapy. The combination CPH + PROC can be used as basis for the elaboration of more effective polychemotherapy schemes. Combination of CPH + PROC + Prospidine and CPH + PROC + CCNU resulted in enhancement of the treatment effect in experimental tumors.
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Experiments on CBA mice immunized with sheep red blood cells have shown that paphencyl, promycil, prospidin and imidazole-4-carboxamide decrease the number of IgM-antibody-forming cells in mouse spleens during the primary immune response. The highest immunodepressant effect was exhibited by paphencyl, while the least by prospidin. The maximum inhibition of the immune response was observed on paphencyl and promycil administration 24 hours after the immunization, that on prospidin administration 24 hours prior to antigen exposure, and that on imidazole-4-carboxamide administration 24 hours prior and 48 hours after the antigenic stimulation. The degree of antibody genesis suppression depends on the dose of paphencyl, promycil and prospidin and does not depend on the dose of imidazole-4-carboxamide. Paphencyl significantly diminishes the number of hemopoietic stem cells in mouse spleens, while prospidin was less active in this respect.
Prospidin--N,N3-di(beta-chloroethyl)-N1,N2-dispirotripiperazinium - is a broad-spectrum antineoplastic drug with low toxicity. Experiments on albino rats with transplanted sarcoma M-1 were made to study the distribution and kinetics of 14C-prospidin labeled in the dispirotripiperazinium part of the molecule. On being given intravenously the drug accumulated for 15 minutes. The maximum value of the differential accumulation ratio (CAR) amounted to 3.34 (kidneys) and 0.16 (thymus). The content of the label in organs and tissues was related both to its presence in the blood and to the penetration into the cell structures. The magnitude of the integral indicator in the kidneys, liver, small intestine, bone marrow, lungs and tumor was considerably higher than in other organs. The accumulation of 14C-prospidin mainly by the lung tissue, bronchi, throat and bone marrow enables a correlation to be elucidated between the accumulation and antineoplastic action in the organs under consideration. The presence of the label in different fragments of the 14C-prospidin molecule (14C-dispirotripiperazinium and 14C-hydroxypropyl grouping) made it possible to establish that the DAR for the former label in organs and tissues 3--6 hours after the drug administration was 2--6 times greater than for the latter. As judged from the integral content of the label, prospidin had begun metabolizing and its biological activity decreased by the time indicated.
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The author's experience with nitrosomethylurea+prospidine treatment in 37 patients having disseminated melanoma is described. The mentioned scheme of the combination therapy is proved to be effective.
The experience of the Moscow Research Institute of Oncology named after P. A. Herzen with the treatment of 368 primary patients with malignant tumors of the upper jaw, and the analysis of the literature data allowed a formulation of basic tendencies in therapy of this affection. These include a wide use of the combination therapy with preoperative radiation treatment; an elaboration of some extended variants of surgical interventions; an improvement of radiation technics, use of drug therapy, mainly as regional chemotherapy associated with radiotherapy. Further elaboration of the early diagnostics is also of importance. Patients in whom malignant tumors of the upper jaw were detected should be treated in specialized oncological departments, specially equipped and having well-trained medical staff.
In 59 patients with malignant skin melanoma, the effect of regional endolymphatic therapy on pathomorphosis of lymphogenic metastases and long-term results of treatment was studied. The essential morphologic changes at the sites of melanoma and higher indices of patients' survival in the group studied when compared to the control group have been noted.
The results of treatment of the patients with I-II stage skin melanoma (including 84 with I stage melanoma of skin of the extremities and trunk, 59--with metastases of melanoblastoma to the regional lymph nodes) who underwent endolymphatic chemotherapy in addition to the radical operation are presented. A statistically significant improval of the results was established when compared with those of the surgical treatment.
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Prospidin and azathioprine were given to 28 and 12 SLE patients, respectively, in a controlled trial which implied subsequent clinical and immunological surveillance for 12 months. The data obtained in the trial provided evidence for true antilupus activity of prospidin in a total dose 3.0-9.8 g. Prospidin brought about improvement with a complete or partial remission of the lupus nephritis in 71%, serious side effects in 21%, lethality in 17.8%, secondary resistance in 10% of the patients treated. The clinical and immunocorrective effects conformed. Compared to azathioprine, prospidin can produce more pronounced and rapid effect, induced more marked immunodepression. It is better tolerated, has no cytopenia effect. The drugs mechanisms of action and criteria of the treatment efficacy are discussed. It is hold valid to use prospidin in long-term maintenance of SLE patients.