title: Phase II trial of neoadjuvant pemetrexed plus cisplatin followed by surgery and radiation in the treatment of pleural mesothelioma.
abstract: BACKGROUND
  Malignant pleural mesothelioma is an aggressive tumor that has a poor prognosis and is resistant to unimodal approaches. Multimodal treatment has provided encouraging results.
  
  
  METHODS
  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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
  
  
  BACKGROUND
  Clinicaltrial.com registrationID #NCT00087698.
authors: Azienda Ospedaliera-Università di Padova, U.O. Chirurgia Toracica, Via Giustiniani 2, 35121 Padova, Italy. federico.rea@unipd.it
authors: Rea
authors: R
authors: Federico
authors: Favaretto
authors: F
authors: Adolfo
authors: Marulli
authors: M
authors: Giuseppe
authors: Spaggiari
authors: S
authors: Lorenzo
authors: DePas Tommaso
authors: DT
authors: Martino
authors: Ceribelli
authors: C
authors: Anna
authors: Paccagnella
authors: P
authors: Adriano
authors: Crivellari
authors: C
authors: Gino
authors: Russo
authors: R
authors: Francesca
authors: Ceccarelli
authors: C
authors: Matteo
authors: Kazeem
authors: K
authors: Gbenga
authors: Marchi
authors: M
authors: Paolo
authors: Facciolo
authors: F
authors: Francesco
mesh_terms: D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D002945:Cisplatin / Q000008:administration & dosage / Q000009:adverse effects; D018572:Disease-Free Survival; D005260:Female; D005971:Glutamates / Q000008:administration & dosage / Q000009:adverse effects; D006147:Guanine / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D008654:Mesothelioma / Q000401:mortality / Q000628:therapy*; D008875:Middle Aged; D020360:Neoadjuvant Therapy / Q000379:methods*; D000068437:Pemetrexed; D010997:Pleural Neoplasms / Q000401:mortality / Q000628:therapy*; D011013:Pneumonectomy; D011878:Radiotherapy
chemical_list: D005971:Glutamates; D000068437:Pemetrexed; D006147:Guanine; D002945:Cisplatin