Malignant Pleural Mesothelioma Treatment - Cisplatin
Single-agent chemotherapy
Doxorubicin is the most frequently investigated chemotherapeutic agent in the treatment of Malignant Pleural Mesothelioma (MPM). Studies have failed to corroborate evidence, however, for encouraging response rates to doxorubicin of up to 20% that had been reported in earlier studies (Aisner and Wiernik, 1981; Antman and Corson, 1985). Likewise, newer anthracyclines such as epirubicin, detorubicin, pirarubicin and mitoxantrone have shown low levels of efficacy and have offered no clinically relevant advantage over doxorubicin (Colbert et al, 1985; Eisenhauer et al, 1986; Sridhar et al, 1989; Kaukel et al, 1990; Magri et al, 1991; van Breukelen et al, 1991; Mattson et al, 1992; Magri et al, 1992). In summary, the overall response rate produced by anthracyclines applied in Malignant Pleural Mesothelioma (MPM) appears to be no higher than 15% and median survival does not exceed 8 months.
Apart from anthracyclines, several studies have investigated the platinum compounds, cisplatin and carboplatin. Single-agent cisplatin resulted in a response rate of merely 14.3% and a median survival of 7.5 months (Zidar et al, 1988). Studies using the newer compound carboplatin resulted in similar response rates ranging between 6 and 16% (Mbidde et al, 1986; Raghavan et al, 1990; Vogelzang et al, 1990).
The alkylating agents cyclophosphamide and mitomycin have shown low-level activity in Malignant Pleural Mesothelioma (MPM) therapy (Bajorin et al, 1987; Sorensen et al, 1985). Promising results initially arising from high-dose ifosfamide therapy (Alberts et al, 1988) could not be confirmed by subsequent studies (Falkson et al, 1992; Zidar et al, 1992; Icli et al, 1996; Krarup-Hansen, 1996; Andersen et al, 1999).
The older vinca alkaloids vinblastine, vincristine and vindesine have demonstrated no activity in the treatment of Malignant Pleural Mesothelioma (MPM) (Kelsen et al, 1983; Boutin et al, 1987; Cowan et al, 1988; Martensson & Sorenson, 1989). Likewise, poor results were shown with oral as well as IV etoposide (Tammilehto et al, 1994; Sahmoud et al, 1997).
The antifolates methotrexate and edatrexate have been the only single agents to produce comparatively better results. A Norwegian study reported a satisfactory response rate of 37% for high-dose methotrexate and a median survival of 11 months, for trial subjects with an epithelial subtype drawing a particular benefit from this chemotherapy option (Solheim et al, 1992). Sequential multicentre phase II studies conducted by the CALGB have evaluated the activity of the folate antagonist edatrexate, with and without leucovorin rescue. Edatrexate produced 25% overall response rates but proved to be relatively toxic. Leucovorin rescue in the control arm led to decreased toxicities, but may also have reduced the agent's efficacy (Kindler et al, 1999). Other antimetabolites like fluorouracil, dihydro-5-azacytidine (DHAC), dideazafolic acid and trimetrexate have shown minor or no activity in the treatment of Malignant Pleural Mesothelioma (MPM) (Harvey et al, 1984; Vogelzang et al, 1994; Vogelzang et al, 1997; Samuels et al, 1998).