Jänne Pasi A, Wozniak Antoinette J, Belani Chandra P, Keohan Mary-Louise, Ross Helen J, Polikoff Jonathan A, Mintzer David M, Ye Zhishen, Monberg Matthew J, Obasaju Coleman K
Department of Medical Oncology, Dana Farber Cancer Institute and Department of Medicine, Brigham and Women's Hospital, Boston, MA 02115, USA.
J Thorac Oncol. 2006 Jul;1(6):506-12.
In a randomized phase III trial, pemetrexed plus cisplatin was associated with improved survival compared with cisplatin alone for patients with malignant pleural mesothelioma (MPM). However, there are limited data available on the efficacy of these and other chemotherapy regimens in patients who have received previous systemic chemotherapy. To gather additional efficacy and safety data of pemetrexed/cisplatin and pemetrexed alone in previously treated patients, we examined patients treated on the Eli Lilly and Company expanded access program (EAP).
Patients with malignant mesothelioma were enrolled in this trial. Of 1056 patients receiving at least one dose of the study drug, 187 (17.7%) were previously treated patients with MPM. Patients were treated every 21 days with pemetrexed 500 mg/m alone (n = 91) or in combination with cisplatin 75 mg/m (n = 96) for a maximum of six cycles. All patients received folic acid and vitamin B12 supplementation and steroid prophylaxis. Serious adverse events (SAEs) were reported by investigators and compiled in a pharmaco-vigilance database for all patients enrolled in the EAP.
Median age of the previously treated pleural mesothelioma subset was 66 years (range, 27-87 years). Based on 153 evaluable patients (a subset of the larger intent-to-treat population of 187), the overall response rate was 32.5% for pemetrexed and cisplatin and 5.5% for pemetrexed alone. The disease control rate (response rate + stable disease) was 68.7% for pemetrexed and cisplatin and 46.6% for pemetrexed alone. Median survival was 7.6 months for pemetrexed plus cisplatin (67% censored) and 4.1 months for pemetrexed alone (55% censored). The most commonly reported serious adverse events in the overall EAP irrespective of causality were dehydration (7.2%), nausea (5.2%), vomiting (4.9%), dyspnea (3.8%), and pulmonary embolism (2.4%).
The data from this EAP study suggest that patients with previously treated MPM can benefit from treatment with pemetrexed alone or in combination with cisplatin. The treatment is associated with acceptable toxicity.
在一项随机III期试验中，对于恶性胸膜间皮瘤（MPM）患者，培美曲塞联合顺铂与单纯使用顺铂相比，可提高生存率。然而，关于这些化疗方案以及其他化疗方案在先前接受过全身化疗的患者中的疗效数据有限。为了收集培美曲塞/顺铂和单纯培美曲塞在先前治疗患者中的更多疗效和安全性数据，我们对礼来公司扩大可及性项目（EAP）中治疗的患者进行了研究。
恶性间皮瘤患者纳入本试验。在1056例接受至少一剂研究药物的患者中，187例（17.7%）为先前接受过治疗的MPM患者。患者每21天接受一次治疗，单独使用培美曲塞500mg/m²（n = 91）或联合顺铂75mg/m²（n = 96），最多六个周期。所有患者均接受叶酸和维生素B12补充以及类固醇预防。研究者报告严重不良事件（SAEs），并将其汇总到EAP所有入组患者的药物警戒数据库中。
先前接受过治疗的胸膜间皮瘤亚组的中位年龄为66岁（范围27 - 87岁）。基于153例可评估患者（187例更大的意向性治疗人群的一个亚组），培美曲塞联合顺铂的总缓解率为32.5%，单纯培美曲塞为5.5%。疾病控制率（缓解率 + 疾病稳定率）培美曲塞联合顺铂为68.7%，单纯培美曲塞为46.6%。培美曲塞联合顺铂的中位生存期为7.6个月（67%删失），单纯培美曲塞为4.1个月（55%删失）。在整个EAP中，无论因果关系如何，最常报告的严重不良事件为脱水（7.2%）、恶心（5.2%）、呕吐（4.9%）、呼吸困难（3.8%）和肺栓塞（2.4%）。
这项EAP研究的数据表明，先前接受过治疗的MPM患者可从单独使用培美曲塞或联合顺铂治疗中获益。该治疗的毒性可接受。
