Long-Term Remissions in Metastatic Malignant Melanoma Following Chemotherapy and Tamoxifen Maintenance

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It is remarkable that patients 1 and 2 developed progressive disease under tamoxifen maintenance (after 17 and 7 months, respectively), but remained in complete remission following local therapy (exstirpation of a kidney metastasis and an adrenal body in patient 1; irradiation of the lumbar spine, the sacrum and the right humerus in patient 2) and continuation of tamoxifen therapy. Four out of these 6 patients had liver metastases, usually indicating a particularly poor prognosis. 2 of them (patients 1 and 2) have shown a continuous complete remission for 16 and 13 years, respectively. Up to now, to our knowledge, there has been only 1 case published with a continuous complete remission of liver metastases for 10 years (following vindesine and interferon) [1]. As potential action mechanisms of tamoxifen in malignant melanoma, induction of apoptosis and inhibition of angiogenesis [2], inactivation of the insulin-like growth factor-1 receptor [3], or inhibition of tumor cell invasion and metastasis through suppression of the PKC/MEK/ERK and PKC/PI3K/ Akt pathways [4] have been discussed. Tamoxifen monotherapy in metastatic melanoma has been reported to induce remissions in about 5% of the patients, in some cases after progression of the disease in the first months of therapy [5]. In combination with chemotherapy, tamoxifen failed to exert an additional therapeutic effect in most studies [6]. But, to our knowledge, no results are published about tamoxifen maintenance following chemotherapy. Given the good tolerability and low costs of the drug, it would be worthwhile to start a clinical trial with a larger number of patients to investigate the potential of tamoxifen maintenance in metastatic malignant melanoma, if possible.

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