EFFICACY AND SAFETY OF HIGH-DOSE CISPLATIN AND CYCLOPHOSPHAMIDE WITH GLUTATHIONE PROTECTION IN THE TREATMENT OF BULKY ADVANCED EPITHELIAL OVARIAN-CANCER
EFFICACY AND SAFETY OF HIGH-DOSE CISPLATIN AND CYCLOPHOSPHAMIDE WITH GLUTATHIONE PROTECTION IN THE TREATMENT OF BULKY ADVANCED EPITHELIAL OVARIAN-CANCER
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DOI：
10.1007/bf00686237
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发表时间：
1990-01-01
影响因子：
3
通讯作者：
ZUNINO, F
中科院分区：
文献类型：
--
作者：
DIRE, F;BOHM, S;ZUNINO, F
最近在晚期卵巢癌中使用大剂量顺铂提高反应率的努力受到不可接受的毒性的限制。基于实验和临床研究表明还原性谷胱甘肽（GSH）对顺铂诱导的毒性具有保护作用，设计了一种包括还原性谷胱甘肽作为化学保护剂的新大剂量方案，旨在提高顺铂的疗效和治疗指标。共有40例连续III期（大体积）和IV期卵巢癌患者接受顺铂（40 mg/m2 /天，连续4天）和环磷酰胺（600 mg/m2 /天）治疗。第4天)。治疗每3-4周重复5个疗程，除非出现进展或严重毒性。每次顺铂给药前，患者接受谷胱甘肽（1500mg /m2）静脉注射，时间超过15分钟，同时标准静脉补水（2000ml液体），不含利尿剂。最初有18例患者尝试减体积手术，经过2-3个疗程后，有16例患者尝试减体积手术；6例患者不能进行手术。3例患者因过早停止治疗而无法评估疗效。总共有23例患者（62%）达到完全临床缓解（16例复诊阴性），总体（完全+部分）缓解率为86%；2例患者在第二次手术后达到无病状态。恶心/呕吐是最严重的急性毒性反应；骨髓抑制可接受。谷胱甘肽可有效预防肾损害。在接受4-5疗程治疗的患者中，不伴有运动功能障碍的神经毒性是最显著的累积毒性（24/32）。本研究结果提示谷胱甘肽是一种安全的大剂量顺铂给药新方法。该方案耐受性良好，对卵巢癌大体积疾病患者非常有效，值得进一步评估。
Recent efforts to improve the response rates in advanced ovarian cancer with the use of high-dose cisplatin have been limited by unacceptable toxicity. Based on experimental and clinical studies indicating that reduced glutathione (GSH) is a protective agent against cisplatin-induced toxicity, a new high-dose regimen including GSH as a chemoprotector was designed in an attempt to improve the efficacy and therapeutic index of cisplatin. A total of 40 consecutive patients with stage III (bulky) and IV ovarian carcinoma were treated with cisplatin (40 mg/m2daily for 4 consecutive days) and cyclophosphamide (600 mg/m2i. v. on day 4). The treatment was repeated every 3–4 weeks for five courses unless progression or severe toxicity occurred. Before each cisplatin administration, patients received GSH (1,500 mg/m2) i. v. over 15 min, with a standard i. v. hydration (2,000 ml fluid) without diuretics. Debulking surgery was initially attempted in 18 patients and, after 2–3 courses, in 16 patients; it could not be carried out in 6 patients. Three patients were not evaluable for response because they prematurely discontinued their treatment. In all, 23 patients (62%) achieved complete clinical remission (negative second-look laparotomy in 16), with an overall (complete + partial) response rate of 86%; 2 patients achieved disease-free status following second surgery. Nausea/vomiting was the most severe acute toxic effect; myelosup-pression was acceptable. Renal impairment was effectively prevented by GSH. Neurotoxicity that was not associated with motor dysfunction was the most significant cumulative toxicity in patients (24/32) receiving 4–5 courses. The results of this study indicate that the use of GSH is a safe new method for high-dose cisplatin administration. This regimen is well-tolerated and very effective in ovarian cancer patients with bulky disease and warrants further evaluation.