Preliminary experience with high-dose cisplatin, reduced glutathione and natural interferon-α in dacarbazine-resistant malignant melanoma
Preliminary experience with high-dose cisplatin, reduced glutathione and natural interferon-α in dacarbazine-resistant malignant melanoma
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DOI：
10.1177/030089169808400110
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发表时间：
1998-01-01
期刊：
影响因子：
--
通讯作者：
Cassata, A
中科院分区：
文献类型：
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作者：
Bajetta, E;Rimassa, L;Cassata, A
目的和背景：恶性黑色素瘤的发病率在许多国家迅速上升，当该病已到晚期时，标准治疗效果甚微。达卡巴津(DTIC)是最有效的化疗药物，总有效率为20%-25%，但持久有效的情况并不常见。关于顺铂(CDDP)在DTIC耐药黑色素瘤中应用的有趣结果已有报道。此外，恶性黑色素瘤是一种免疫原性肿瘤，是生物反应调节剂(BRM)治疗的潜在靶点。本研究的目的是评估大剂量顺铂联合谷胱甘肽(GSH)限制铂相关毒性的化疗免疫治疗方案和天然干扰素-α(IFN-α)治疗DTIC耐药的转移性黑色素瘤的疗效和耐受性。方法：GSH 1500 mg/m(2)静脉滴注。顺铂40 mg/m(2)静脉注射。干扰素-α每周3次，连续4天，最多6个疗程，每周3次，最长持续12个月。结果：12名患者进入了这项II期试验。由于与治疗相关的毒性，应计停止。10例可评价疗效，2例部分缓解，分别持续5+和9+个月，2例病情稳定，持续3+和8+个月。由于与治疗相关的副作用，这些患者都没有完成治疗计划。结论：该方案对DTIC耐药的转移性黑色素瘤似乎只有部分有效。血液学和非血液学(恶心和呕吐，外周神经毒性和虚弱)副作用显著，GSH在限制CDDP相关神经毒性方面无效。因此，没有迹象表明使用这种方案作为转移性黑色素瘤的二线治疗，这些令人失望的结果突出了对新的治疗方法的迫切需要。
Aims and background: The incidence of malignant melanoma is rapidly increasing in many countries, and when this disease has reached advanced stages, standard therapies have little impact. Dacarbazine (DTIC) is the most effective chemotherapeutic agent with an overall response rate of 20-25%, but durable responses are uncommon. Interesting results with the use of cisplatin (CDDP) have been reported in DTIC-resistant melanoma. Moreover, malignant melanoma is an immunogenic tumor and a potential target for biological response modifier (BRM) therapies. The aim of the present study was to evaluate the efficacy and tolerability of a chemo-immunotherapeutic regimen including high-dose CDDP combined with glutathione (GSH) to limit platinum-related toxicity, and natural interferon-alpha (IFN-alpha) in patients with DTIC-resistant metastatic melanoma. Methods: The treatment schedule included GSH 1,500 mg/m(2) i.v. and CDDP 40 mg/m(2) i.v. for 4 consecutive days every 3 weeks, with a maximum of 6 courses, and IFN-alpha 3 MIU i.m, 3 times a week, continuative for a maximum of 12 months. Results: Twelve patients were enrolled in this phase II trial. Accrual was stopped due to treatment-related toxicity. Ten patients were evaluable for response; there were 2 partial responses, lasting 5+ and 9+ months, respectively, and 2 cases of stable disease, lasting 3+ and 8+ months. None of these patients completed the therapeutic program due to treatment-related side effects. Conclusions: This regimen seems to be only partially active in DTIC-resistant metastatic melanoma. Hematologic and non-hematologic (nausea and vomiting, peripheral neurotoxicity, and asthenia) side effects are significant and GSH is not effective in limiting CDDP-related neurotoxicity in pretreated patients. Therefore, there is no indication to employ this regimen as second-line treatment in metastatic melanoma and these disappointing results highlight the urgent need for new therapeutic approaches.