Buzaid A C, Murren J R, Durivage H J
Department of Medicine, Yale New Haven Hospital, Yale University School of Medicine, Connecticut 06510.
Cancer. 1991 Sep 15;68(6):1238-41. doi: 10.1002/1097-0142(19910915)68:6<1238::aid-cncr2820680609>3.0.co;2-#.
In an attempt to increase the antitumor effect of cisplatin (50 mg/m2) and dacarbazine (350 mg/m2), each repeated on days 1 to 3 every 4 weeks in patients with metastatic melanoma, tamoxifen was added to the regimen. Before the first course of chemotherapy, the patients received a loading dose of tamoxifen (100 mg orally twice a day for 7 days), followed by a maintenance dose of 10 mg orally twice a day and continued throughout the treatment. Aspirin (325 mg orally every other day) was administered at the same time as the tamoxifen in an attempt to reduce the risk of thromboembolic events. The activity of high-dose cisplatin with dacarbazine and tamoxifen was disappointing. Of 23 evaluable patients, only three responded--an overall response rate of 13% (95% confidence limits, 0% to 27%). These responses consisted of one pathologic complete remission in a patient with nodal metastases, one clinical complete remission in a patient with a very large pelvic mass, and one partial response in another patient with nodal metastases. The duration of responses was 12+, 4, and 4 months, respectively. These data do not support a significant interaction between tamoxifen and cisplatin or dacarbazine. Assuming that tamoxifen is important in the cisplatin, dacarbazine, and carmustine combination, as suggested by others, the most relevant interaction may be between tamoxifen and carmustine.
为提高顺铂（50mg/m²）和达卡巴嗪（350mg/m²）的抗肿瘤效果（二者在转移性黑色素瘤患者中每4周于第1至3天重复使用），在该方案中加入了他莫昔芬。在第一个化疗疗程前，患者接受他莫昔芬负荷剂量（口服100mg，每日2次，共7天），随后为维持剂量，口服10mg，每日2次，并在整个治疗过程中持续使用。阿司匹林（口服325mg，隔日1次）与他莫昔芬同时给药，以降低血栓栓塞事件的风险。高剂量顺铂联合达卡巴嗪及他莫昔芬的活性令人失望。在23例可评估患者中，仅3例有反应，总缓解率为13%（95%置信区间，0%至27%）。这些反应包括1例伴有淋巴结转移患者的病理完全缓解、1例盆腔巨大肿块患者的临床完全缓解以及另1例伴有淋巴结转移患者的部分缓解。缓解持续时间分别为12个月以上、4个月和4个月。这些数据不支持他莫昔芬与顺铂或达卡巴嗪之间存在显著相互作用。假设如其他人所建议的，他莫昔芬在顺铂、达卡巴嗪和卡莫司汀联合方案中很重要，那么最相关的相互作用可能存在于他莫昔芬与卡莫司汀之间。
