Abstract
BackgroundMalignant pleural mesothelioma is an aggressive tumor that has a poor prognosis and is resistant to unimodal approaches. Multimodal treatment has provided encouraging results.MethodsPhase 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.ResultsFifty-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.ConclusionsThe 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.Trial registrationClinicaltrial.com registrationID #NCT00087698.
Highlights
Malignant pleural mesothelioma is an aggressive tumor that has a poor prognosis and is resistant to unimodal approaches
Secondary efficacy objectives were to assess: 1- and 2year eventfree survival (EFS) rates; progression-free survival (PFS), defined as the time from study enrollment to the first date of disease progression or death as a result of any cause (PFS was censored at the date of the last follow-up visit for patients who were still alive and who have not progressed); overall survival (OS), defined as the time from study enrollment to time of death from any cause (OS was censored at the date of last follow-up for patients who were still alive); and time to tumor response (TTR), defined as the time from study enrollment to the first observation of an objective tumor response
The present study was designed to test the feasibility and assess the efficacy and safety of the combination of pemetrexed and cisplatin followed by extrapleural pneumonectomy (EPP) and hemithoracic radiation
Summary
Malignant pleural mesothelioma is an aggressive tumor that has a poor prognosis and is resistant to unimodal approaches. Malignant pleural mesothelioma (MPM) is an aggressive tumor originating from the superficial serosal cells of pleural cavities that has long been considered rare. The incidence of malignant mesothelioma is currently reported to range from 7 to 40 cases per million people, but it is believed that it will increase in the 10 to 15 years [1]. MPM rapidly spreads to adjacent structures of the thoracic cavity. This explains why the majority of patients present with locally advanced or metastatic disease: 48% are in stage III and 40% are in stage IV [2,3]. The median overall survival (OS) from diagnosis is 12 months, ranging from 8 months in stage IV patients to 40 months in stage I patients [4]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
