Local and Systemic Therapies for Malignant Pleural Mesothelioma

Abstract

Malignant pleural mesothelioma (MPM) is a challenging disease to treat with median overall survival times ranging between 9-17 months for all stages of disease. Recent clinical trials have improved our understanding of the biology of MPM. However, survival results are still not ideal. For early-stage MPM, patients should be evaluated for trimodality therapy in an experienced cancer center. If treating off-protocol, MPM patients should receive a surgical staging evaluation. The decision to proceed with surgical resection also should be considered after an extensive and thorough pulmonary and cardiac evaluation. If deemed a good surgical candidate, patients should receive surgical resection (pleurectomy/decortication or extrapleural pneumonectomy), adjuvant radiation therapy (hemithoracic external beam or intensity modulated radiation therapy), and either neoadjuvant or adjuvant chemotherapy (cisplatin-pemetrexed for 4 cycles). The optimal precise sequence of the trimodality is unclear and should be decided upon by a multidisciplinary consensus for each individual patient. In general, clinical trial participation should be encouraged. Several trials are currently underway to examine intraoperative therapies, vaccines, immunotherapy additions, and novel radiation therapy techniques. Advances in the field of MPM are reliant on participation in clinical trials and identifying biomarkers that are predictive for response to systemic therapies and prognostic for survival benefit.

In Vitro and In Vivo Anti-tumoral Effects of the Flavonoid Apigenin in Malignant Mesothelioma

“…The majority of intracavitary chemotherapy trials have used platinum-based regimens, but despite the local administration of the drug side effects occurred (Chang and Sugarbaker, 2004). Intrapleural gene therapy and immunotherapy have been also employed but these therapies appear to be more advantageous in patients with small tumors (Gomez and Tsao, 2014). The combination of targeted therapies has shown to increase anti-tumor activities (Favoni and Florio, 2011).…”

The role of intracavitary therapies in the treatment of malignant pleural mesothelioma

“…Concurrently, different studies explored the pharmacokinetic of HITHOC using cisplatin alone or in association with other drugs as Anthracyclines (8,(14)(15)(16)(17), confirming its feasibility and its low systemic exposure; doxorubicin was reported to have a low penetration into the tissues compared to cisplatin; moreover, direct cardiac toxicity of doxorubicin has been discussed, but no clear evidences are available. Nevertheless, there is no consensus on the correct doses of drugs used for HITHOC which usually change in every institution's protocols; cisplatin has been administered intracavitary at a dose of up to 225 mg/m 2 when used alone and doxorubicin is usually administered at a dose of 80 mg/m 2 (18). Chan (7) …”

Synergistic anti‐tumor efficacy of immunogenic adenovirus ONCOS‐102 (Ad5/3‐D24‐GM‐CSF) and standard of care chemotherapy in preclinical mesothelioma model

“…MM affects the pleura (85.5%), peritoneum (13.2%), pericardium (0.5%) and tunica vaginalis (0.8%) . MM tumors are often poorly responsive to standard therapies and incidence is constantly increasing worldwide . The low incidence of MM has for a long time limited the discovery of new drugs, therefore, new treatment modalities are highly needed …”

“…3 MM tumors are often poorly responsive to standard therapies and incidence is constantly increasing worldwide. 2,[4][5][6][7] The low incidence of MM has for a long time limited the discovery of new drugs, 3 therefore, new treatment modalities are highly needed. 8 Oncolytic adenoviruses are promising and potentially powerful immunotherapy tools for treatment of cancer.…”