Current concepts in chemotherapy for malignant pleural mesothelioma

The aim of this study was to provide an overview of the most active single agents and combination regimens in malignant pleural mesothelioma (MPM).

Literature on English-language trials in humans was searched on Medline until October 2007. Indexing terms were malignant pleural mesothelioma and chemotherapy.

Trials with > or =15 patients and with data on activity were included.

Detorubicin and pirarubicin have response rates (RRs) of 22%-26%, epirubicin of 5%-15%, docetaxel of 5%-23% and vinorelbine of 24%. Other active agents were ifosfamide (3%-24%) and mitomycin C (21%). Carboplatin and cisplatin have an overall RR of 11% in three studies and 17% in four studies, respectively. Antimetabolites were active, including methotrexate (37%), raltitrexed (21%), edatrexate (16%-25%) and pemetrexed (15%). With respect to combination chemotherapy regimens, only cisplatin with either pemetrexed or raltitrexed has been compared with other substances, in both cases to cisplatin monotherapy. Both showed a survival advantage, which was statistically significant in the trial including pemetrexed, suggesting that chemotherapy improved survival in MPM. No studies have compared chemotherapy with the best supportive care alone, and none has compared different combination chemotherapy regimens with each other.

A number of single-agent cytotoxics posess moderate activity against MPM. A number of platinum-based combination chemotherapy regimens show similar activities, but none has been compared with another combination. Cisplatin with either raltitrexed or pemetrexed has improved survival compared with cisplatin alone, and may be used as a reference treatment in randomized trials. Targeted agents should be explored in order to further improve the outcome.