Immunomodulatory effect of tamoxifen in combination with CCNU, cisplatinum, and dacarbazine in melanoma patients

Tamoxifen, a nonsteroidal anti-estrogen, is effecient not only in adjuvant therapy for node-positive and node-negative breast cancer, but also has sev eral attractive pharmacological features which caused an interest in testin g it as a immunomodulator. In this study, we present our results on the imm unomodulatory activity of Tamoxifen in combination with CCNU, Cisplatinum, and Dacarbazine in patients with metastatic malignant melanoma. The chemoth erapeutic regimen contained CCNU 100 mg/m(2) on day 1, Dacarbazine - 220 mg /m(2) from day 2 to 4, Cisplatinum - 25 mg/m(2) - from day 2 to 4, and Tamo xifen - 60 mg/m(2) - from day 2 to 4. As a whole, Tamoxifen with CCNU, Cisp latinum, and Dacarbazine did not cause Immunosuppression of T-lymphocytes. However, this combination resulted in a slight impairment of the functional activity of T-lymphocytes as measured by PHA-induced DNA synthesis. Follow ing chemotherapy individual changes of the mitogen activity of T-lymphocyte s and their levels were detected, depending on the actual status of the imm une system. Patients with low levels of T-lymphocytes before treatment (B g roup) responded to chemotherapy with an increase in T-lymphocytes, whereas in those with normal levels (A-group) the T-lymphocytes declined. The respo nse to mitogen stimulation declined in both groups of patients compared to pretreatment levels. We conclude that the chemotherapy with Tamoxifen can d ifferentially influence T-lymphocytes and their responsiveness to mitogen s timulation in patients with malignant melanoma, depending on the pretreatme nt levels. This should be taken into account when planning new combinations with Tamoxifen.