The evidence for tamoxifen and chemotherapy as treatment for metastatic melanoma.

Tamoxifen, an oestrogen antagonist routinely used in the treatment of breast cancer, has been used in clinical trials for patients with melanoma since the late 1970s. Following initial promise as a single agent for the treatment of metastatic melanoma, tamoxifen was first combined with chemotherapy in this setting in 1984. Since then, numerous phase II studies have combined tamoxifen with different chemotherapeutic agents, with some suggesting that tamoxifen significantly improves the efficacy of cisplatin-containing regimens. Overall response rates range from 8 to 60%. Several randomised trials also have been completed, with response rates of 12-30%. One such study showed statistically significant improvements in response rate and survival when tamoxifen was added to dacarbazine; however, other studies have not observed these benefits with the addition of tamoxifen to cisplatin-containing regimens. At present, the author's opinion is that the strength of evidence does not support the use of tamoxifen in combination with cisplatin-containing chemotherapy for the treatment of metastatic melanoma. Controversy remains as to whether the strength of evidence from the randomised trials outweighs the combined evidence from numerous nonrandomised trials. Resolution of this controversy may depend on the results of the North Central Cancer Therapy Group and/or a common agreement as to relative strength of evidence from clinical trials of different designs.