Recent advances in the treatment of malignant pleural mesothelioma

Our plain-English summary of Recent advances in the treatment of malignant pleural mesothelioma, by S.S. Ramalingam, C.P. Belani (Journal of Thoracic Oncology, 2008).

The study

• Authors: S.S. Ramalingam, C.P. Belani
• Journal: Journal of Thoracic Oncology
• Published: 2008;3(9):1056-64
• Type of article: Review
• Cited by: 24 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

Malignant pleural mesothelioma clinically manifests after decades of initial exposure to etiologic agents, such as asbestos, and presents with nonspecific symptoms such as dyspnea, pain, or weight loss. In patients with limited, resectable disease, surgical therapy with extrapleural pneumonectomy or pleurectomy is recommended, although, it is unclear which approach is superior. Radiation has a limited role and is used primarily for palliation. The palliative efficacy of traditional chemotherapeutic agents and combination regimens is modest at best. The combination of cisplatin and pemetrexed, a novel multitargeted antifolate agent, is the approved "standard of care" for patients with unresectable malignant pleural mesothelioma. A number of molecularly targeted agents are currently under evaluation for mesothelioma such as the Histone deacetylase (HDAC) inhibitors that have demonstrated promising anticancer activity. Vorinostat, a small molecule inhibitor of HDAC, which targets select members of class I and II HDACs, has shown early evidence of activity and is currently being evaluated in a randomized study for patients who progress with standard therapy for advanced mesothelioma. It is hoped that the HDAC inhibitors and other novel targeted agents will pave the way for improved outcomes for patients with this disease.

In plain English

This article was a narrative review, not a new study. The authors summarised published and ongoing research on treating malignant pleural mesothelioma, which they described as linked to asbestos. They covered surgery, radiation, chemotherapy and newer targeted drugs. They reported that no randomised trial had compared the two main operations (extrapleural pneumonectomy and pleurectomy), so it was unclear which was better. They described radiation as not recommended as the main treatment but used to relieve symptoms such as chest pain. In a cited phase III trial of 456 patients, median survival was 12.1 months with cisplatin plus pemetrexed and 9.3 months with cisplatin alone. In other cited trials, the EGFR-blocking drugs gefitinib and erlotinib produced no objective responses, and adding bevacizumab to chemotherapy did not give a statistically significant survival difference. In early studies of vorinostat that included 13 patients with advanced disease, 2 had partial responses. The authors concluded that cisplatin with pemetrexed was the standard of care for advanced disease, and that results with HDAC inhibitors had renewed interest in new drugs.

We wrote this plain-English summary from the full article with the help of AI, and a second AI model checked each sentence against the article. It is not the authors' wording; the abstract and the article are their own account.

What the study did and found

• Design: Narrative review ("concise review") of published and ongoing treatment studies; no search method or selection criteria were described
• Who was studied: Published studies and ongoing trials of treatment for patients with malignant pleural mesothelioma (MPM)
• Exposure: Treatments for malignant pleural mesothelioma: surgery (extrapleural pneumonectomy, pleurectomy with decortication), radiation, chemotherapy, and molecularly targeted agents. Asbestos was mentioned only as background, as a cause of the disease; no fiber types were discussed.
• Main results:
  • Surgery: the authors stated that no prospective randomised comparison of extrapleural pneumonectomy and pleurectomy had been performed. In a cited series of 663 patients (Flores et al.), postoperative mortality was 7% after extrapleural pneumonectomy and 4% after pleurectomy.
  • Radiation: the authors stated that radiation was not recommended as primary therapy, but could be used to relieve chest pain. In one cited study, pain improved in 13 of 19 evaluable patients at 1 month after treatment, but the benefit was short lived.
  • Chemotherapy: in a cited randomised phase III trial of 456 patients (Vogelzang et al.), median survival was 12.1 months with cisplatin plus pemetrexed and 9.3 months with cisplatin alone. Response rates were 42% and 17% respectively.
  • Chemotherapy: in a cited phase III trial (van Meerbeeck et al.), median overall survival was 11.4 months with cisplatin plus raltitrexed and 8.8 months with cisplatin alone.
  • Chemotherapy versus symptom control: in a cited randomised trial of active symptom control with or without chemotherapy, there was a non-significant trend toward longer median survival with chemotherapy (8.5 versus 7.6 months). The authors noted that the trial had low statistical power.
  • Targeted drugs: in cited phase II studies, gefitinib and erlotinib (EGFR inhibitors) produced no objective responses. With erlotinib, disease was stabilised in 15 of 33 patients with measurable disease.
  • Targeted drugs: in a cited randomised phase II study, adding bevacizumab to cisplatin and gemcitabine gave median progression-free survival of 6.9 versus 6.0 months and median overall survival of 15.6 versus 14.7 months. The difference was not statistically significant.
  • HDAC inhibitors: in cited phase I studies of oral vorinostat, which included 13 patients with advanced MPM (12 previously treated with chemotherapy), 2 patients had objective partial responses. This led to a randomised trial comparing vorinostat with placebo.
• The authors' conclusion: The authors concluded that surgery is considered standard therapy for early-stage disease and that radiation has palliative benefit. For advanced disease, they stated that cisplatin plus pemetrexed improves survival and quality of life and constitutes the standard of care. They found early results with EGFR and VEGF inhibitors disappointing, while data on HDAC inhibitors had renewed enthusiasm for testing new agents.

Topics

The National Library of Medicine indexes this study under subjects our site covers: Mesothelioma.

Medical terms in this study, explained in our Lexicon: Pleural Mesothelioma, Dyspnea, Extrapleural Pneumonectomy (EPP), Palliative Care, Cisplatin, Pemetrexed (Alimta), Antifolate, Unresectable.

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