IN-VIVO, SYNERGESTIC INHIBITION OF MAT-LYLU RAT PROSTATIC ADENOCARCINOMA GROWTH BY POLYAMINE DEPRIVATION AND LOW-DOSE CYCLOPHOSPHAMIDE

Polyamine deprivation in vivo produces significant tumor growth inhibi tion of the hormone-resistant, metastatic Dunning Mat-LyLu murine pros tatic carcinoma. In order to produce a cytotoxic effect in addition to the cytostatic effect of polyamine deprivation, various chemotherapy regimens, combined with drug-containing polyamine-deficient chow (DC-P DC), were assessed, Triple chemotherapy combining methotrexate, cyclop hosphamide and vindesine; and monochemotherapy with high-dose cyclopho sphamide (90 mg kg(-1)) and low-dose cyclophosphamide (20 mg . kg(-1)) were studied alone and in combination with DC-PDC, A variant of DC-PD C excluding the polyamine oxidase inhibitor MDL 72527 was also studied in combination with low-dose cyclophosphamide. The triple-chemotherap y regimen alone or in combination with polyamine deprivation was effec tive on tumor growth inhibition but was also toxic. High-dose cyclopho sphamide alone produced significant tumor growth inhibition and an inc rease in life span. High-dose cyclophosphamide in combination with DC- PDC was also effective on tumor growth but was also toxic. Low-dose cy clophosphamide alone was moderately effective on tumor growth inhibiti on with a marginal increase in life span. When combined with polyamine deprivation, results with low-dose cyclophosphamide compared favourab ly with those of high-dose cyclophosphamide alone and prevented the fo rmation of lung metastases. The polyamine oxidase inhibitor does not a ppear to be mandatory to achieve this effect if DC-PDC is combined wit h low-dose cyclophosphamide. Polyamine deprivation appears to be an im portant tool in anticancer therapy, allowing the use of reduced doses of cytotoxic agents with the same antitumoral efficacy.