Malignant Pleural Mesothelioma: Current Treatment Modalities and Advances

Malignant pleural mesothelioma (MPM) is an aggressive form of cancer that affects the lining of the lungs, commonly caused by asbestos exposure. Due to its aggressive nature and often late-stage diagnosis, treatment options have historically been limited, with relatively poor outcomes. However, advancements in medical science have led to a wider range of therapies, from surgical options to novel pharmacotherapies. This article aims to provide a comprehensive understanding of the current treatment modalities available for MPM.

Surgical Treatments

Surgery remains a cornerstone in the management of early-stage MPM. Extrapleural Pneumonectomy (EPP) is one of the most extensive surgical procedures, involving the removal of the diseased lung, portions of the diaphragm, and the pleura. A study published in the Journal of Thoracic and Cardiovascular Surgery by Sugarbaker et al. reported that patients undergoing EPP, in combination with chemotherapy and radiation, had a median survival rate of 19 months, compared to those who opted for non-surgical treatments.

Pleurectomy/Decortication (P/D) is another surgical option. It is less radical than EPP and focuses on removing only the pleura and tumor mass. The MARS-2 trial indicated that P/D in combination with chemotherapy could offer survival benefits comparable to EPP but with fewer surgical complications.

Chemotherapy

Chemotherapy is often employed either as a standalone treatment or in conjunction with surgery. The most common regimen includes a combination of cisplatin and pemetrexed. A landmark trial by Vogelzang et al. demonstrated a median survival of 12.1 months for patients treated with this combination, as opposed to 9.3 months for those receiving cisplatin alone.

Immunotherapy

The advent of immunotherapy has brought renewed hope. Checkpoint inhibitors like pembrolizumab (Keytruda) and nivolumab (Opdivo) have been evaluated in several clinical trials. A study by Scherpereel et al. in the Lancet Respiratory Medicine found that nivolumab had a disease control rate of 50% when used as a second-line treatment in relapsed MPM patients.

malignant pleural mesothelioma treatment

Targeted Therapies

Targeted therapies aim at molecular pathways driving cancer progression. Agents like bevacizumab (Avastin), a monoclonal antibody, have shown promise. The MAPS trial revealed that adding bevacizumab to standard chemotherapy extended life expectancy by nearly three months.

Multimodal Treatment

A multimodal approach, which combines surgery, chemotherapy, and sometimes radiation or immunotherapy, is becoming increasingly standard. Research from the MARS trial emphasized that such an approach could significantly increase median survival rates.

Future Prospects and Conclusion

Novel treatment modalities are currently under investigation. One such promising field is gene therapy, aiming to correct or replace faulty genes associated with cancer progression. Clinical trials are ongoing to assess the efficacy of such therapies. Another promising field is the application of Artificial Intelligence in the early diagnosis and treatment planning for MPM, which could revolutionize patient outcomes.

While MPM remains a formidable adversary, the arsenal of treatments has expanded over the years. Advancements in surgery, the advent of novel pharmacotherapies like immunotherapy, and a move towards multimodal treatment have all contributed to improved patient outcomes. Ongoing research continues to offer hope for even more effective treatments in the future.

Sources

- Sugarbaker, D. J., et al. "Resection margins, extrapleural nodal status, and cell type determine postoperative long-term survival in trimodality therapy of malignant pleural mesothelioma: Results in 183 patients." Journal of Thoracic and Cardiovascular Surgery, 117(1), 54--65, 1999.

- MARS-2 trial. "Pleurectomy/decortication (Extended Pleurectomy) Versus no Pleurectomy Decortication in the Surgical Management of Malignant Pleura Mesothelioma." ClinicalTrials.gov Identifier: NCT02040272, 2019.

- Vogelzang, N. J., et al. "Phase III Study of Pemetrexed in Combination With Cisplatin Versus Cisplatin Alone in Patients With Malignant Pleural Mesothelioma." Journal of Clinical Oncology, 21(14), 2636--2644, 2003.

- Scherpereel, A., et al. "Nivolumab or nivolumab plus ipilimumab in patients with relapsed malignant pleural mesothelioma (IFCT-1501 MAPS2): a multicentre, open-label, randomised, non-comparative, phase 2 trial." Lancet Respiratory Medicine, 7(6), 487-498, 2019.

- Zalcman, G., et al. "Bevacizumab for newly diagnosed pleural mesothelioma in the Mesothelioma Avastin Cisplatin Pemetrexed Study (MAPS): a randomised, controlled, open-label, phase 3 trial." The Lancet, 387(10026), 1405-1414, 2016.

- MARS trial. "Surgery in Treating Patients With Malignant Pleural Mesothelioma: Results From the Mesothelioma and Radical Surgery (MARS) Randomized Feasibility Study." The Lancet Oncology, 12(8), 763-772,