Gottlieb J A, Drewinko B
Cancer Chemother Rep. 1975 May-Jun;59(3):621-8.
During the past 3 years, eight hospitals and one cooperative study group have reported their initial clinical results with cis-dichlorodiammineplatinum (II). The most popular clinical schedule was 15-25 mg/m2/day for 5 days repeated every 3-4 weeks. Almost all patients had extremely advanced disease. Of 323 patients in whom response could be evaluated, there were 12 complete responses, 25 partial responses (greater than 50% decrease in tumor size), and 23 improvements (greater than 50% decrease in tumor size) for a 19% overall response rate. The tumor most sensitive to cis-dichlorodiammineplatinum (II) was testicular carcinoma in which seven complete responses, three partial responses, and three improvements were observed in 16 patients treated at Roswell Park Memorial Institute. Other sensitive tumors were lymphoma (63% response and improvements), squamous cell carcinoma of the head and neck (41% response and imporvements), and ovarian carcinoma (40% response and improvements). Complete responses were also seen in one patient with thyroid carcinoma and two with bladder carcinoma, while partial remissions were recorded in two patients with breast carcinoma and one patient each with acute myelogenous leukemia, endometrial carcinoma, renal carcinoma, malignant thymoma, neuroblastoma, adenocarcinoma of the lung, and an undifferentiated tumor of unknown origin. Five major types of toxicity were encountered: gastrointestinal, hematopoietic, immunosuppressive, otologic, and renal, with the last two generally the most serious. Serial audiometry testing can generally warn of the otologic toxicity and thus prevent permanent acoustic damage. Renal toxicity, which is similar to that seen with heavy-metal poisoning, appears to be dose related, cumulative, and only partly reversible, thus, severely limiting the repeated administration of cis-dichlorodiammineplatinum (II). Recent laboratory studies suggest that combination chemotherapy with this drug may be rewarding. Studies of this nature should be pursued along with attempts to find more effective less toxic platinum compounds.
在过去3年中，8家医院和1个合作研究小组报告了顺二氯二氨铂（II）的初步临床结果。最常用的临床方案是15 - 25毫克/平方米/天，连用5天，每3 - 4周重复一次。几乎所有患者的病情都已发展到极为严重的程度。在323例可评估疗效的患者中，有12例完全缓解，25例部分缓解（肿瘤大小缩小超过50%），23例病情改善（肿瘤大小缩小超过50%），总有效率为19%。对顺二氯二氨铂（II）最敏感的肿瘤是睾丸癌，在罗斯韦尔帕克纪念研究所接受治疗的16例患者中，观察到7例完全缓解、3例部分缓解和3例病情改善。其他敏感肿瘤包括淋巴瘤（63%有缓解和病情改善）、头颈部鳞状细胞癌（41%有缓解和病情改善）以及卵巢癌（40%有缓解和病情改善）。1例甲状腺癌患者和2例膀胱癌患者出现了完全缓解，而2例乳腺癌患者、1例急性髓性白血病患者、1例子宫内膜癌患者、1例肾癌患者、1例恶性胸腺瘤患者、1例神经母细胞瘤患者、1例肺腺癌患者和1例来源不明的未分化肿瘤患者出现了部分缓解。出现了5种主要类型的毒性反应：胃肠道毒性、造血系统毒性、免疫抑制毒性、耳毒性和肾毒性，其中后两种通常最为严重。连续听力测定通常可以警示耳毒性，从而预防永久性听力损害。肾毒性与重金属中毒所见相似，似乎与剂量相关、具有累积性且仅部分可逆，因此严重限制了顺二氯二氨铂（II）的重复给药。最近的实验室研究表明，该药物联合化疗可能会有成效。应开展此类研究，并努力寻找毒性更低、更有效的铂化合物。
