Current concepts in chemotherapy for malignant pleural mesothelioma

Abstract

Objectives: The aim of this study was to provide an overview of the most active single agents and combination regimens in malignant pleural mesothelioma (MPM). Data Source: Literature on English-language trials in humans was searched on Medline until October 2007. Indexing terms were malignant pleural mesothelioma and chemotherapy. Study Selections: Trials with Ն15 patients and with data on activity were included. Results: 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. Conclusions: 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.Please cite this paper as: Sørensen JB. Current concepts in chemotherapy for malignant pleural mesothelioma.

COX-2 specific inhibitors enhance the cytotoxic effects of pemetrexed in mesothelioma cell lines

“…Chemotherapy has been limited to use in palliative therapy of the disease and as an adjunct to radical surgery. A number of cytotoxic compounds have been assessed and typically give tumour response rates in the range of 10-30% when used as single agents [2][3][4]. Combination regimens have been investigated in order to increase the benefit.…”

“…Combination regimens have been investigated in order to increase the benefit. Cisplatin and carboplatin are among the most active single drugs and usually included in combination therapy regimens [4,5]. Vinorelbine, a semisynthetic vinca alkaloid derived from vinblastine, has also attracted interest.…”

Cisplatin and vinorelbine first-line chemotherapy in non-resectable malignant pleural mesothelioma

“…A large number of single agents have been tested for activity in MPM (Berghmans et al, 2002;Ellis et al, 2006;Sørensen, 2008). The third generation vinca alkaloid vinorelbine has attracted interest in a phase II trial using vinorelbine 30 mg m À2 i.v.…”

“…Chemotherapy for MPM is challenging, although several cytotoxic agents have been tested and the rates of objective tumour response have ranged from 10 to 30% with monotherapy (Tomek and Manegold, 2004). Cisplatin and carboplatin are both active and thus usually included in the most used combination chemotherapy regimens for MPM (Sørensen, 2008).…”

Physicochemical and pharmacokinetic properties of polymeric films loaded with cisplatin for the treatment of malignant pleural mesothelioma

“…Cisplatin mono-therapy demonstrated an overall response rate of 14% at a dose of 100 mg/m 2 given every 21 days in patients with diffuse malignant mesothelioma. At higher doses (e.g., 80 mg/m 2 weekly), cisplatin achieved a response rate of 36% with significant discontinuation (34%) due to toxic effects (12,13). Hyaluronate and chitosan are polysaccharides that have been employed for drug delivery applications because of their remarkable biopharmaceutical properties.…”