Malignant pleural mesothelioma

Our plain-English summary of Malignant pleural mesothelioma, by H.L. Kindler (Current Treatment Options in Oncology, 2000).

The study

• Author: H.L. Kindler
• Journal: Current Treatment Options in Oncology
• Published: 2000;1(4):313-26
• Type of article: Review
• Cited by: 20 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

Despite innumerable trials of surgery, radiotherapy, and countless chemotherapeutic drugs, it is unclear whether any intervention has had a significant impact on more than a few highly selected patients with malignant pleural mesothelioma. Because most patients die of respiratory failure from extensive disease progression in the thorax, treatment usually includes attempts at local control. Unfortunately, radiotherapy is associated with significant complications in pleural mesothelioma, and surgery is feasible in only a small percentage of patients. Although there have been several single-institution reports of combined-modality therapy with extrapleural pneumonectomy, postoperative radiation, and chemotherapy in which prolonged survival has been observed, most patients with malignant pleural mesothelioma have locally advanced disease, advanced age, or comorbid medical illnesses that preclude aggressive surgery. Therefore, the use of a systemic anticancer agent is the only treatment option for most patients with malignant pleural mesothelioma. Evaluation of effective chemotherapy regimens for this disease has been hampered by many factors. Because mesothelioma is an uncommon malignancy, most studies have enrolled small numbers of patients, and few trials have been randomized. The disease is heterogeneous, yet until recently there was no single staging system that could reliably predict survival, nor is there a universally accepted set of prognostic criteria for selecting a uniform group of patients. Response assessment has been limited by the inherent difficulties of reproducibly measuring pleural-based disease. The real impact of systemic chemotherapy on the natural history of malignant mesothelioma is still uncertain because phase III trials comparing chemotherapy with best supportive care have not yet been completed. Although nearly every class of cytotoxic agent has been evaluated in mesothelioma, response rates of greater than 20% have not been consistently demonstrated for any drug. The most active drug classes are the antifolates, the anthracyclines, and the platinums. Doxorubicin has historically been considered the gold-standard chemotherapy, although its true response rate is likely only 15%. The most active commercially available drug for mesothelioma so far appears to be gemcitabine. Although gemcitabine has a limited role as a single agent, it is quite active in combination with a platinating agent. The impressive 48% response rate reported for the combination of gemcitabine with cisplatin in a single phase II study has made this regimen the new standard of care for off-protocol treatment of this disease, although this trial still requires validation. With the recent introduction of several new agents with definite activity in this disease, the therapeutic nihilism previously associated with malignant pleural mesothelioma is gradually being replaced by a cautious optimism. Early trials of angiogenesis inhibitors, gene therapy, and vaccines offer additional avenues for treatment. As we begin to incorporate these active new drugs with each other and in adjuvant and neoadjuvant treatment regimens, there is reason to believe that superior results for patients with malignant pleural mesothelioma can be achieved in the near future.

In plain English

This article was a review of treatments for malignant pleural mesothelioma. It opened with the author's opinion statement. It did not report new research. Instead it summarized earlier published trials and case series of chemotherapy, radiotherapy, surgery and experimental therapies. The author wrote that response rates above 20% had not been consistently shown for any drug. The author also noted that no phase III study comparing chemotherapy with best supportive care had been completed. Among the studies reviewed, an Eastern Cooperative Oncology Group review found that doxorubicin given alone produced a response in 14% of 51 patients. A single phase II trial of gemcitabine with cisplatin reported a 48% response rate, a median survival of 9.5 months and an estimated 1-year survival of 41%. In one surgical series of highly selected patients treated with extrapleural pneumonectomy followed by chemotherapy and radiation, two- and five-year survival were 45% and 22%. The author noted that most studies were small, few were randomized, and tumor response was hard to measure. The author concluded that pessimism about treatment was gradually giving way to cautious optimism.

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 treatment for malignant pleural mesothelioma, introduced by the author's opinion statement; no new data were collected
• Who was studied: No study population of its own; the review drew on published trials and series of patients with malignant pleural mesothelioma
• Exposure: Asbestos exposure was not studied. The article reviewed treatments (chemotherapy, radiotherapy, surgery and emerging therapies). Asbestos appears only as background in the introduction.
• Main results:
  • In the author's assessment of the published trials, no drug had consistently produced response rates above 20%
  • No phase III study comparing survival with chemotherapy versus best supportive care had been completed
  • In a retrospective review of Eastern Cooperative Oncology Group experience (another study), single-agent doxorubicin had activity of 14% in 51 patients
  • In a phase II trial of gemcitabine plus cisplatin by Byrne et al. (another study), the response rate was 48%, median survival 9.5 months, and estimated 1-year survival 41%
  • In a phase II trial of mitomycin, vinblastine and cisplatin by Middleton et al. (another study), the tumor response rate was 20%, but 62% of patients had symptom benefit
  • In a series by Sugarbaker and Norberto (another study) of highly selected patients treated with extrapleural pneumonectomy followed by chemotherapy and radiation, two- and five-year survival were 45% and 22%
  • In a small randomized trial by Boutin et al. (another study), prophylactic radiotherapy after thoracoscopy reduced local recurrence along procedure tracks from 40% to 0%
• The authors' conclusion: The author concluded that, with the arrival of several new drugs with definite activity, earlier pessimism about treating malignant pleural mesothelioma was gradually being replaced by cautious optimism. The author added that the gemcitabine-cisplatin result had become the standard off-protocol treatment but still needed validation.
• Limitations the authors state:
  • The author stated that most studies of mesothelioma treatment enrolled small numbers of patients and few were randomized
  • The author stated that judging tumor response was limited by the difficulty of reproducibly measuring disease along the pleura
  • The author stated that the IMIG staging system still required validation in prospective studies

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, Disease Progression, Thorax, Extrapleural Pneumonectomy (EPP), Chemotherapy, Mesothelioma, Staging, Malignant Mesothelioma.

Related studies

• Clinical features and current treatment of diffuse malignant pleural mesothelioma — V.W. Rusch (1995)
• Recent advances in the treatment of malignant pleural mesothelioma — S.S. Ramalingam, C.P. Belani (2008)
• Combined chemotherapy with cytotoxic and targeted compounds for the management of human malignant pleural mesothelioma — R.E. Favoni, T. Florio (2011)
• Malignant pleural mesothelioma: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up — R.A. Stahel, W. Weder, et al. (2010)
• Optimal Therapy of Advanced Stage Mesothelioma — M.M.J. Disselhorst, S.J.A. Burgers, et al. (2017)
• SEOM clinical guidelines for the treatment of malignant pleural mesothelioma (2020) — E. Nadal, J. Bosch-Barrera, et al. (2021)

Browse more research in Current Treatment Options in Oncology, or return to medical research.