Email updates

Keep up to date with the latest news and content from BMC Cancer and BioMed Central.

Open Access Research article

Phase II trial of neoadjuvant pemetrexed plus cisplatin followed by surgery and radiation in the treatment of pleural mesothelioma

Rea Federico1*, Favaretto Adolfo2, Marulli Giuseppe1, Spaggiari Lorenzo3, DePas Tommaso Martino4, Ceribelli Anna5, Paccagnella Adriano6, Crivellari Gino6, Russo Francesca7, Ceccarelli Matteo7, Kazeem Gbenga8, Marchi Paolo7* and Facciolo Francesco9

Author affiliations

1 Azienda Ospedaliera-Università di Padova, U.O. Chirurgia Toracica, Via Giustiniani 2, 35121 Padova, Italy

2 Istituto Oncologico Veneto, U.O. Oncologia Medica 2, Via Gattamelata 64, 35128 Padova, Italy

3 Istituto Europeo di Oncologia, Div. Chirurgia Toracica, Via Ripamonti 435, 20141 Milan, Italy

4 Istituto Europeo di Oncologia, Div. Oncologia Medica, Via Ripamonti 435, 20141 Milan, Italy

5 Istituto Nazionale Tumori “Regina Elena”, Div. Oncologia Medica, Via Chianesi 53, 00144 Rome, Italy

6 Ospedale dell’Angelo, Div. Oncologia Medica, Via Paccagnella 11, 30174 Mestre, (VE), Italy

7 Eli Lilly Italia, Via Gramsci 731/733, 50019 Sesto, Fiorentino, (FI), Italy

8 Eli Lilly UK, Erl Wood Manor, Windhlesham, Surrey GU20 6PH, United Kingdom (former employee

9 Istituto Nazionale Tumori “Regina Elena”, Div. Chirurgia Toracica, Via Chianesi 53, 00144 Rome, Italy

For all author emails, please log on.

Citation and License

BMC Cancer 2013, 13:22  doi:10.1186/1471-2407-13-22

Published: 16 January 2013

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.

Trial registration

Clinicaltrial.com registrationID #NCT00087698.

Keywords:
Pemetrexed; Pleural mesothelioma; Chemotherapy; Surgery; Radiation