The effectiveness of cis-platinum, cyclophosphamide and melphalan in treating disseminated tumor cells in mice

Abstract

Both B16 melanoma and Lewis lung carcinoma growing in C57/Bl mice spontaneously metastasize to the lungs and other organs. When the tumors are grown in the mouse tail to a specific volume and amputated, the spontaneously disseminated tumor cells can then be independently treated. The effects of a single dose of cyclophosphamide (200 mg/kg), cis-platinum (6 mg/kg) and melphalan (10 mg/kg) on the appearance of pulmonary and other metastases were measured. The cis-platinum treatment was shown to reduce the number and incidence of metastases of both tumors at various times after treatment. The antimetastatic effectiveness of cis-platinum against these two tumors was increased when 2.4 mg/kg was administered each day for five consecutive days after amputation of the primary. Cyclophosphamide, when administered at two-thirds maximum tolerated dose, had a small promoting effect on the number and incidence of pulmonary metastases of Lewis lung carcinoma, whereas, applied in the same dose, it had efficacy in the treatment of disseminated B16 melanoma and inhibited appearance of both pulmonary and lymph-node metastases. When melphalan was administered in single- and multiple-dose regimens, the number and incidence of metastases of both tumors increased at various times after primary tumor amputation. These data suggest that melphalan can promote the growth of disseminated tumor cells in both the lungs and other sites and that some systemic chemotherapies may result in promotion instead of suppression of metastatic disease.

Melphalan inhibits adenoma development through modulating the expression of K-ras-specific markers in K-ras Tg mice

“…In a number of investigations sufficient evidence for the carcinogenicity of melphalan in experimental animals was shown. When administered by intraperitoneal injection, melphalan caused lymphosarcoma, lung tumors in mice and peritoneal sarcoma in rats (14,15). In this study, we investigated whether K-ras-specific biomarkers would be modulated by melphalan, and whether melphalan would exert an influence on a genotoxic carcinogenic or an anti-cancer effect in lung tissues of K-ras transgenic mice.…”