Systemic treatment of malignant pleural mesothelioma

Our plain-English summary of Systemic treatment of malignant pleural mesothelioma, by F. Grosso, G.V. Scagliotti (Future Oncology, 2012).

The study

• Authors: F. Grosso, G.V. Scagliotti
• Journal: Future Oncology
• Published: 2012;8(3):293-305
• Type of article: Review
• Cited by: 22 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

Malignant pleural mesothelioma is a rare malignancy with a dismal prognosis. The clinical management of most of the patients with this disease is quite challenging, and, overall, the therapeutic strategy has not yet benefited from the recent advances in molecular biology. Randomized evidence supports the use of cisplatin in combination with pemetrexed or raltitrexed as first-line treatments. In elderly patients with comorbidities cisplatin may be replaced by carboplatin because of a lesser burden of toxicities. The role of second-line chemotherapy is unproven, although pemetrexed can be regarded as the standard option in pemetrexed-naive patients and therapeutic rechallenge with pemetrexed may be considered in selected patients with prolonged disease control after first-line therapy. Targeted therapies failed to demonstrate any substantial activity; however, immunotherapies may complement other treatment strategies. In summary, there is an unmet clinical need and innovative approaches to select new potentially active drugs are highly warranted.

In plain English

This article was a review of published research on drug treatment of malignant pleural mesothelioma, covering chemotherapy, targeted drugs and immunotherapy. It did not study asbestos exposure. Among the reviewed studies, the EMPHACIS trial compared cisplatin plus pemetrexed with cisplatin alone in 456 patients who had not had chemotherapy. Median overall survival was 12.1 versus 9.3 months. In a trial of cisplatin plus raltitrexed versus cisplatin alone, the article reports median survival of 11.4 versus 8.8 months. The authors described these differences as of borderline statistical significance. In previously treated patients who had not had pemetrexed, a reviewed trial found that pemetrexed improved disease control and progression-free survival compared with best supportive care, but showed no survival or quality-of-life advantage. The authors reported that none of the targeted drugs had consistently shown activity. A 661-patient vorinostat trial did not significantly extend survival. The authors concluded that cisplatin plus pemetrexed is the standard first-line chemotherapy, that carboplatin may replace cisplatin when toxicity is a concern, and that there is no standard second-line chemotherapy after pemetrexed-based treatment.

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 of published clinical studies of systemic (drug) treatment
• Who was studied: Patients with malignant pleural mesothelioma enrolled in selected published Phase II and III trials and expanded-access programs. The article does not describe how the studies were chosen.
• Exposure: Not an asbestos exposure study. It reviewed treatments: chemotherapy (cisplatin, carboplatin, pemetrexed, raltitrexed, gemcitabine, vinorelbine and others), targeted therapies and immunotherapies.
• Main results:
  • In the reviewed EMPHACIS trial (456 chemotherapy-naive patients), median overall survival was 12.1 months with cisplatin plus pemetrexed versus 9.3 months with cisplatin alone.
  • In the reviewed raltitrexed trial (250 patients randomized; 213 with measurable disease), cisplatin plus raltitrexed versus cisplatin alone gave a response rate of 24 versus 11% and median overall survival of 11.4 versus 8.8 months.
  • The authors described the raltitrexed trial differences as of borderline statistical significance, probably because the study was underpowered.
  • In the reviewed second-line trial (243 previously treated, pemetrexed-naive patients), pemetrexed versus best supportive care gave a disease control rate of 59 vs 19% and median progression-free survival of 3.6 vs 1.5 months.
  • In the same second-line trial, pemetrexed showed no advantage in quality of life or overall survival.
  • The authors reported that none of the new targeted drugs reviewed had consistently shown activity in malignant pleural mesothelioma.
  • In a reviewed Phase III trial of 661 previously treated patients, vorinostat versus placebo did not significantly extend progression-free survival (6.3 vs 6.1 weeks) or overall survival (30.7 vs 27.1 weeks).
  • The authors stated that carboplatin may replace cisplatin if treatment-related toxicities become a concern.
  • The authors stated that there is no standard second-line chemotherapy for patients whose first-line pemetrexed-based therapy failed.
• The authors' conclusion: The authors concluded that cisplatin plus pemetrexed is the standard first-line chemotherapy for malignant pleural mesothelioma.

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, Prognosis, Cisplatin, Pemetrexed (Alimta), Raltitrexed, Carboplatin, Chemotherapy, First-line Therapy.

Related studies

• In Australia, patients and government at odds over mesothelioma treatment costs — V. Burkitt (2007)
• Systemic treatment of malignant pleural mesothelioma: new agents in clinical trials raise hope of relevant improvements — D.C. Christoph, W.E. Eberhardt (2014)
• Future developments in the management of malignant pleural mesothelioma — P.A. Zucali, F. De Vincenzo, et al. (2009)
• Raltitrexed plus cisplatin is cost-effective compared with pemetrexed plus cisplatin in patients with malignant pleural mesothelioma — B. Woods, N. Paracha, et al. (2012)
• Systemic chemotherapy with pemetrexed and cisplatin for malignant peritoneal mesothelioma: a single institution experience — G. Lainakis, F. Zagouri, et al. (2011)
• Antimetabolites in the treatment of advanced pleural mesothelioma: a network meta-analysis of randomized clinical trials — D. Tassinari, C. Cherubini, et al. (2017)

Browse more research in Future Oncology, or return to medical research.