Azienda Ospedaliera-Università di Padova, U.O. Chirurgia Toracica, Via Giustiniani 2, 35121 Padova, Italy.
BMC Cancer. 2013 Jan 16;13:22. doi: 10.1186/1471-2407-13-22.
Malignant pleural mesothelioma is an aggressive tumor that has a poor prognosis and is resistant to unimodal approaches. Multimodal treatment has provided encouraging results.
Phase II, open-label study of the combination of chemotherapy (pemetrexed 500 mg/m²+cisplatin 75 mg/m² IV every 21 days × 3 cycles), followed by surgery (en-bloc extrapleural pneumonectomy, 3-8 weeks after chemotherapy) and hemithoracic radiation (total radiation beam 54 Gy, received 4-8 weeks post-surgery). The primary endpoint was event-free survival, defined as the time from enrollment to time of first observation of disease progression, death due to any cause, or early treatment discontinuation.
Fifty-four treatment-naïve patients with T1-3 N0-2 malignant pleural mesothelioma were enrolled, 52 (96.3%) completed chemotherapy, 45 (83.3%) underwent surgery, 22 (40.7%) completed the whole treatment including 90-day post-radiation follow-up. The median event-free survival was 6.9 months (95%CI: 5.0-10.5), median overall survival was 15.5 months (95%CI 11.0-NA) while median time-to-tumor response was 4.8 months (95%CI: 2.5-8.0). Eighteen (33.3%) and 13 (24.1%) patients were still event-free after 1 and 2 years, respectively. The most common treatment-emergent adverse events were nausea (63.0%), anemia (51.9%) and hypertension (42.6%).Following two cardiopulmonary radiation-related deaths the protocol was amended (21 [38.9%] patients were already enrolled in the study): the total radiation beam was reduced from 54 Gy to 50.4 Gy and a more accurate selection of patients was recommended.
The combination of pemetrexed plus cisplatin followed by surgery and hemithoracic radiation is feasible and has a manageable toxicity profile in carefully selected patients. It may be worthy of further investigation.
Clinicaltrial.com registrationID #NCT00087698.
恶性胸膜间皮瘤是一种侵袭性肿瘤，预后较差，对单一治疗方法具有抗性。多模式治疗已提供了令人鼓舞的结果。
这项 II 期、开放标签的研究纳入了化疗（培美曲塞 500mg/m²+顺铂 75mg/m² IV 每 21 天×3 个周期）联合治疗的患者，随后进行手术（化疗后 3-8 周行整块胸膜外全肺切除术）和半胸部放疗（总放射剂量 54Gy，术后 4-8 周内接受）。主要终点是无事件生存，定义为从入组到首次观察到疾病进展、任何原因导致的死亡或早期治疗中断的时间。
共纳入了 54 例未经治疗的 T1-3 N0-2 期恶性胸膜间皮瘤患者，52 例（96.3%）完成了化疗，45 例（83.3%）接受了手术，22 例（40.7%）完成了包括 90 天放疗后随访的整个治疗。中位无事件生存时间为 6.9 个月（95%CI：5.0-10.5），中位总生存时间为 15.5 个月（95%CI 11.0-NA），中位肿瘤反应时间为 4.8 个月（95%CI：2.5-8.0）。18 例（33.3%）和 13 例（24.1%）患者在 1 年和 2 年后仍无事件发生。最常见的治疗相关不良事件为恶心（63.0%）、贫血（51.9%）和高血压（42.6%）。由于出现了两例与心肺放疗相关的死亡事件，该方案进行了修订（已有 21 例[38.9%]患者入组研究）：总放射剂量从 54Gy 减少到 50.4Gy，并推荐更准确地选择患者。
培美曲塞联合顺铂治疗后行手术和半胸部放疗在经过精心选择的患者中是可行的，且具有可管理的毒性特征。它可能值得进一步研究。
Clinicaltrial.com 注册号 NCT00087698。
