"Phase II Study: Palliative Treatment With Liposomal Doxorubicin Plus Cisplatin for Patients With Malignant Pleural Mesothelioma "

Background:

Malignant pleural mesothelioma (MPM) is an invasive primary neoplasm associated with a rapid progression. It is usually diagnosed in the fifth to seventh decades of life, with a strong male predominance. 80% of the patients with MPM have a history of asbestos exposure. MPM develops only in 10% of the people with asbestos exposure, suggesting that other factors may be important in the development of this malignancy. MPM is classified into three pathological types: epithelial, sarcomatoid, and mixed. The epithelial type represents 50% of all the cases whether the sarcomatoid type the15%. Clinically the sarcomatoid type is related to a poorer prognosis compared with epithelial or mixed types MPM presents unique challenges with regard to diagnosis, staging, and treatment. Survival rates are approximately 6 months in patients without surgical treatment. 90% of the patients with MPM are not candidates for a surgical treatment because they arrived at advanced stages or with a poor lung function. In addition, surgery as a single modality has failed to improve survival, and several researches have explored the use of combined modality therapy incorporating radiation and chemotherapy. Given that the prognosis for patients with advanced MPM is poor regardless of the type of anticancer treatment, palliation of symptoms has been the primary goal. Chemotherapy remains the main palliative therapeutic modality, although either surgical intervention or local radiation therapy may be useful for the local control of pain or symptoms often associated with pleural fluid accumulation.

Most single chemotherapeutic agents have been tested in MPM obtaining response rates of < 20%. The impact of chemotherapy on the survival of patients with MPM remains uncertain. Platinum analogues have been extensively studied in MPM both single and combined regimens. There have been studies of patients with MPM treated with cisplatin 60 mg/m2 and doxorubicin 60 mg/m2 on day 1 with a 3 or 4 week interval demonstrating response rates of 20 to 25% with and overall survival of 10 months.

Liposomal doxorubicin (LD) consists on doxorubicin encapsulated in liposomes that are composed of phosphatidylcholine and cholesterol. LD can extravasate into tumors with abnormal vascular endothelium but may not penetrate normal tissues lowering its toxicity and increasing its efficiency. Combining LD with cisplatin could be an effective new chemotherapy treatment for MPM.

Objective: