Ong S T, Vogelzang N J
Department of Medicine, University of Chicago, IL, USA.
J Clin Oncol. 1996 Mar;14(3):1007-17. doi: 10.1200/JCO.1996.14.3.1007.
We reviewed the published literature of clinical studies in malignant pleural mesothelioma, including phase II trials of the newer antifolates and plant derivatives, as well as older single-agent and combination chemotherapy trials. We excluded trials with less than 15 patients, although we have mentioned smaller trials in the text to make a specific point, as well as ones that show promise. We have also included confidence intervals when cited in the original reports, or calculated them when absent.
No drugs have consistently induced a response greater than 20%. Higher response rates have been reported with detorubicin, high-dose methotrexate, and edatrexate at 26%, 37%, and 25%, respectively, but these have yet to be confirmed. Agents that produce response rates in 10% to 20% of patients include doxorubicin, epirubicin, mitomycin, cyclophosphamide, ifosfamide, cisplatin, and carboplatin. Combination chemotherapy trials do not demonstrate a consistently greater response rate than single-agent trials. However, the combination of doxorubicin, cisplatin, bleomycin, and mitomycin demonstrated a response rate of 44% (95% confidence interval, 27% to 63%), but this remains unconfirmed. Intrapleural therapy using interferon gamma, particularly for small-volume disease, shows promise.
The successful treatment of unresectable pleural mesothelioma awaits the discovery of active drugs. Recent trials of high-dose methotrexate and other antifolates are encouraging. Newer agents, including suramin, should be evaluated in phase II trials. Off-protocol combination therapy cannot be recommended over single-agent therapy, but studies that use combinations of the newer agents should be conducted.
我们回顾了已发表的关于恶性胸膜间皮瘤临床研究的文献，包括新型抗叶酸药物和植物衍生物的II期试验，以及早期的单药和联合化疗试验。我们排除了患者人数少于15例的试验，不过在文中提及了一些较小规模的试验以阐述特定观点或显示出前景的试验。我们还纳入了原始报告中引用的置信区间，若未提及则进行计算。
尚无药物能持续诱导出超过20%的缓解率。据报道，多柔比星、高剂量甲氨蝶呤和依达曲沙的缓解率较高，分别为26%、37%和25%，但这些结果尚未得到证实。能使10%至20%的患者产生缓解率的药物包括多柔比星、表柔比星、丝裂霉素、环磷酰胺、异环磷酰胺、顺铂和卡铂。联合化疗试验并未显示出始终高于单药试验的缓解率。然而，多柔比星、顺铂、博来霉素和丝裂霉素联合使用时缓解率为44%（95%置信区间，27%至63%），但这一结果仍未得到证实。使用γ干扰素进行胸膜内治疗，特别是对于少量疾病，显示出前景。
不可切除胸膜间皮瘤的成功治疗有待发现有效的药物。近期高剂量甲氨蝶呤和其他抗叶酸药物的试验令人鼓舞。包括苏拉明在内的新型药物应在II期试验中进行评估。不推荐非方案规定的联合治疗优于单药治疗，但应开展使用新型药物联合治疗的研究。
