A Deep Dive into Specific Mesothelioma Treatments

Mesothelioma is an aggressive and rare form of cancer that primarily develops in the lining of the lungs, abdomen, or heart. The predominant cause of mesothelioma is exposure to asbestos, a naturally occurring mineral used in construction, shipbuilding, and other industries. Although advances in treatments for other forms of cancer have been substantial, mesothelioma remains a challenging condition to manage effectively. Over the years, the primary treatment modalities for mesothelioma have been surgery, chemotherapy, and radiation therapy. However, recent advances in medical research have introduced targeted therapies and immunotherapies into the treatment landscape. This article provides an in-depth examination of these specific treatments for mesothelioma, emphasizing their benefits, limitations, and the ongoing research to improve therapeutic options for patients.

Traditional Treatments

Surgery and Chemotherapy

Surgery is often the first-line treatment for mesothelioma patients who are diagnosed at an early stage. The types of surgery vary depending on the location of the tumor, the stage of the cancer, and the patient's overall health. Extrapleural Pneumonectomy (EPP) and Pleurectomy/Decortication (P/D) are the primary surgical options for malignant pleural mesothelioma, the most common form of the disease. A study by Sugarbaker et al., published in the Journal of Thoracic and Cardiovascular Surgery, reported that the median survival rate for patients undergoing EPP, in combination with chemotherapy and radiation therapy, was around 19 months. P/D, a less radical option, focuses on preserving lung tissue and is often followed by radiation or chemotherapy to destroy remaining cancer cells. The MARS-2 trial, published in ClinicalTrials.gov, has shown that patients undergoing P/D had similar survival rates to those receiving EPP, but with fewer surgical complications.

Chemotherapy is usually applied either as an adjuvant or as a standalone treatment. The combination of cisplatin and pemetrexed is often used, and according to a study by Vogelzang et al. in the Journal of Clinical Oncology, patients treated with this regimen had a median survival of 12.1 months, compared to 9.3 months for those treated with cisplatin alone.

Emerging Treatments

Immunotherapy and Targeted Therapy

The field of immunotherapy has been transformative for various types of cancer, and its application to mesothelioma has been the subject of considerable research. Checkpoint inhibitors, specifically drugs like pembrolizumab (Keytruda) and nivolumab (Opdivo), have shown promising outcomes. A phase 2 clinical trial by Scherpereel et al., published in the Lancet Respiratory Medicine, demonstrated that the disease control rate was about 50% when nivolumab was used as a second-line treatment in patients with relapsed malignant pleural mesothelioma.

Targeted therapies aim to attack specific cellular mechanisms that contribute to cancer growth. Bevacizumab (Avastin) is one such agent that targets vascular endothelial growth factor (VEGF), inhibiting the blood supply to the tumor. The MAPS trial, published in The Lancet, showed that adding bevacizumab to standard chemotherapy extended median overall survival by 2.7 months.

Multimodal Approaches and Future Directions

A multimodal approach that combines surgery, chemotherapy, and possibly immunotherapy or targeted therapy, has shown the most promise in increasing survival rates and improving the quality of life for mesothelioma patients. Data from the MARS trial, published in The Lancet Oncology, indicates that a multimodal approach could significantly extend the median survival rate.

In the realm of research, significant strides are being made in understanding the genetic and molecular underpinnings of mesothelioma. This has paved the way for the exploration of gene therapy, a treatment modality that aims to correct or replace the faulty genes responsible for cancer development. Although this field is still in its infancy, early clinical trials suggest that gene therapy could become a viable treatment option in the future.

Conclusion

Despite being a rare and challenging cancer to treat, mesothelioma has seen a gradual expansion in its treatment options. While surgical interventions and chemotherapy remain the mainstay, the advent of immunotherapy and targeted therapy is providing new avenues for improving patient outcomes. Multimodal approaches that combine various treatments seem to offer the most promise. Ongoing research in gene therapy and other emerging treatments suggests that even more effective and personalized treatment options may soon be available for mesothelioma patients.

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