Cocconi G, Bella M, Calabresi F, Tonato M, Canaletti R, Boni C, Buzzi F, Ceci G, Corgna E, Costa P
Italian Oncology Group for Clinical Research, Ospedale Maggiore, Parma.
N Engl J Med. 1992 Aug 20;327(8):516-23. doi: 10.1056/NEJM199208203270803.
Endocrine factors may affect the clinical course of malignant melanoma and the response to the treatment of this disease. The presence of estrogen receptors in melanomas has been suggested, and occasional responses to antiestrogen therapy have been reported.
We randomly assigned 117 patients with metastatic malignant melanoma to treatment with dacarbazine alone or dacarbazine in combination with tamoxifen. The overall rate of response, measured objectively, was higher (28 percent vs. 12 percent, P = 0.03) and survival was longer (median, 48 vs. 29 weeks, P = 0.02) among the patients who received dacarbazine plus tamoxifen than among those who received dacarbazine alone. Among women, both the response rate (38 percent vs. 10 percent, P = 0.04) and the median survival (69 vs. 30 weeks, P = 0.008) were better with dacarbazine plus tamoxifen than with dacarbazine alone, whereas among men the differences were smaller and not statistically significant. Among the patients given dacarbazine alone, there were no significant differences between women and men in response rate (10 percent vs. 13 percent) or survival (30 vs. 27 weeks), whereas among those given dacarbazine plus tamoxifen, women had better outcomes, as indicated by both response rate (38 percent vs. 19 percent, P = 0.15) and survival (69 vs. 31 weeks, P = 0.02). When we analyzed the Quetelet body-mass index (the weight in kilograms divided by the square of the height in meters) as an indirect indicator of the levels of endogenous estrogens in postmenopausal women and in men, survival was not affected by the body-mass index in the group given dacarbazine alone, whereas in the group given dacarbazine plus tamoxifen, survival was longer among patients whose Quetelet index was above the median value than among those with a Quetelet index lower than the median value (60 vs. 26 weeks, P less than 0.001).
In the treatment of metastatic malignant melanoma, dacarbazine plus tamoxifen is more effective than dacarbazine alone, as indicated by both the response rate and the median survival; the difference in efficacy is among women.
内分泌因素可能影响恶性黑色素瘤的临床病程以及对该疾病治疗的反应。有人提出黑色素瘤中存在雌激素受体，并且有报道称偶尔会出现对抗雌激素治疗的反应。
我们将117例转移性恶性黑色素瘤患者随机分为单纯接受达卡巴嗪治疗组或达卡巴嗪联合他莫昔芬治疗组。客观测量的总体缓解率，接受达卡巴嗪加他莫昔芬治疗的患者高于单纯接受达卡巴嗪治疗的患者（28%对12%，P = 0.03），生存期也更长（中位数分别为48周和29周，P = 0.02）。在女性患者中，达卡巴嗪加他莫昔芬的缓解率（38%对10%，P = 0.04）和中位生存期（69周对30周，P = 0.008）均优于单纯达卡巴嗪治疗，而在男性患者中，差异较小且无统计学意义。在单纯接受达卡巴嗪治疗的患者中，女性和男性的缓解率（10%对13%）或生存期（30周对27周）无显著差异，而在接受达卡巴嗪加他莫昔芬治疗的患者中，女性的结局更好，缓解率（38%对19%，P = 0.15）和生存期（69周对31周，P = 0.02）均显示如此。当我们将体重指数（体重千克数除以身高米数的平方）作为绝经后女性和男性内源性雌激素水平的间接指标进行分析时，单纯接受达卡巴嗪治疗组的生存期不受体重指数影响，而在接受达卡巴嗪加他莫昔芬治疗组中，体重指数高于中位数的患者生存期长于体重指数低于中位数的患者（60周对26周，P＜0.001）。
在转移性恶性黑色素瘤的治疗中，达卡巴嗪加他莫昔芬比单纯达卡巴嗪更有效，无论是缓解率还是中位生存期均显示如此；疗效差异主要体现在女性患者中。
