Review articleMalignant mesothelioma: options for management
Section snippets
Staging
Staging of malignant mesothelioma is important for predicting survival and determining proper treatment. Unfortunately, until recently, there was no widely accepted staging system. Several groups have proposed staging systems, including Butchart [15], Chahinian [10], Sugarbaker [16], and the International Union against Cancer. These different systems are based on stage I–IV classifications or tumor node metastasis (TNM) staging. The most commonly used system in the past was that of Butchart,
Chemotherapy
Chemotherapy has limited efficacy in malignant mesothelioma. Over the past 45 years, scores of controlled studies, case reports, and retrospective analyses have compared single drug and combination therapies. Most of these have been small, single-institution trials of single agents or combination regimens [20], [21], [22]. In some reports, mesotheliomas have been included in phase II studies of sarcoma therapy. Consistently, the maximal response rate seen with any single chemotherapeutic agent
Radiation therapy
External radiation alone is unsuccessful in extending survival. There is modest regression of gross disease in many studies; however, no study has shown that survival is prolonged [24], [83], [84]. Laboratory studies show that mesothelioma is not radio-resistant; however, there are many reasons why pleural tumors are not conducive to radiation therapy.
Effective irradiation for mesothelioma requires enormous field sizes, essentially encompassing the entire hemithorax and mediastinum. Much can be
Surgery
Two surgical operations are important in the management of diffuse malignant mesothelioma: a debulking procedure (pleurectomy with or without decortication) and radical surgery (extrapleural pneumonectomy). One of the earliest attempts to resect a mesothelioma was made by Eiselberg in Germany in 1922, when an “endothelioma of the pleura” was removed from a 46-year-old man. He recommended radical surgery, but removed only the fourth through eighth ribs and a portion of the lung. An extrapleural
Results
Single-modality treatment—whether chemotherapy, radiation, or surgery—is believed to be of limited value in treating mesothelioma. Although there are numerous reports involving over 800 patients, it is difficult to assess the effect of surgical resection because of the diversity of the procedures [99], [100], [101]. Adjuvant therapies and combined modalities are being employed synergistically to improve efficacy, with some success [5], [102], [103], [104], [105], [106], [107], [108]. Bimodal
Emerging modalities
Regardless of the modality used, conventional forms of treatment for malignant mesothelioma have proven disappointing. Only 20% of tumors can be approached surgically, chemotherapy has limited results, and the neoplasm appears to be radioresistant. However, other modes of treatment are emerging, including immunotherapy, immunoconjugate therapy, and chemohyperthermia. In addition, gene therapy and photodynamic therapy provide even more sophisticated means of mesothelioma management [102], [131],
Palliative management
Palliative treatment is often the only help a thoracic surgeon can offer patients with mesothelioma. The two major symptoms addressed are pain and shortness of breath.
Once an effusion has developed, it is persistent and returns rapidly after simple drainage. Several liters may be removed in a matter of weeks [185]. Diuretics do not prevent reaccumulation. With repeat drainage, thickening of the pleura begins to occur, which in turn leads to difficulty in aspiration because of the development of
Summary
In the past, there has been a tendency to think of diffuse malignant pleural mesothelioma as one disease in therapeutic terms, regardless of histological type and tumor stage. This does not happen with other tumors, yet it is equally illogical and inappropriate in mesothelioma. As with other tumors, early diagnosis—while the disease is still in stage I, or even at an in situ stage—must be the goal so that therapy can be maximized, particularly if immunotherapy or gene therapy is to be used.
References (189)
- et al.
Malignant pleural mesothelioma treatment: the current state of the art
Cancer Treat Rev
(1988) - et al.
Prognostic factors in diffuse malignant pleural mesothelioma. A study of 167 patients
Chest
(1988) - et al.
Extrapleural pneumonectomy in the setting of a multimodality approach to malignant mesothelioma
Chest
(1993) - et al.
Gemcitabine for malignant mesothelioma: a phase II trial by the Cancer and Leukemia Group B
Lung Cancer
(2001) Phase II trials of malignant mesothelioma: a commentary and update
Lung Cancer
(1994)Studies concerning high dose ifosfamide to patients suffering from malignant mesothelioma
Lung Cancer
(1996)Studies concerning high dose ifosfamide to patients suffering from malignant mesothelioma
Lung Cancer
(1996)- et al.
Combination raltitrexed (Tomudex(R))-oxaliplatin: a step forward in the struggle against mesothelioma? The Institut Gustave Roussy experience with chemotherapy and chemo-immunotherapy in mesothelioma
Eur J Cancer
(2000) - et al.
Phase II study of a short course of weekly high-dose cisplatin combined with long-term oral etoposide in pleural mesothelioma
Ann Oncol
(1995) - et al.
Phase I clinical and pharmacokinetic study of the oral platinum analogue JM216 given daily for 14 days
Ann Oncol
(1998)
High-dose paclitaxel plus G-CSF for malignant mesothelioma: CALGB phase II study 9234
Ann Oncol
Randomised phase II study of cisplatin-etoposide versus infusional carboplatin in advanced non-small-cell lung cancer and mesothelioma
Ann Oncol
Treatment of malignant mesothelioma with methotrexate and vinblastine, with or without platinum chemotherapy
Chest
Treatment of malignant mesothelioma with epirubicin and ifosfamide: a phase II cooperative study
Ann Oncol
Raltitrexed (Tomudex) in combination with platinum-based agents and/or anthracyclines: preliminary results of phase I clinical trials
Eur J Cancer
Caelyx in malignant mesothelioma: a phase II EORTC study
Ann Oncol
A phase II trial of dose-escalated doxorubicin and ifosfamide/mesna in patients with malignant mesothelioma
Ann Oncol
Combination chemotherapy with cisplatin-vinblastine in malignant mesothelioma
Lung Cancer
Intrapleural chemotherapy without pleurodesis for malignant pleural effusions. LCSG Trial 861
Chest
Multimodality treatment programs for malignant pleural mesothelioma using high-dose hemithorax irradiation
Int J Radiat Oncol Biol Phys
Factors influencing the outcome of radiotherapy in malignant mesothelioma of the pleura–a single-institution experience with 189 patients
Int J Radiat Oncol Biol Phys
The role of palliative radiotherapy in malignant mesothelioma
Clin Oncol
Surgical approach to pleural diffuse mesothelioma in Japan
Lung Cancer
Current approach to malignant mesothelioma of the pleura
Chest
Extrapleural pneumonectomy for diffuse malignant pleural mesothelioma. A treatment option in selected cases?
Jpn J Thorac Cardiovasc Surg
Therapeutic approach to malignant mesothelioma
Chest
Contemporary management of malignant pleural mesothelioma
Oncologist
Malignant pleural mesothelioma: a disease unaffected by current therapeutic maneuvers
J Clin Oncol
Diffuse malignant pleural mesothelioma: options in surgical treatment
Compr Ther
Treatment and survival in diffuse malignant pleural mesothelioma: a study of 83 cases from the Massachusetts General Hospital
Anticancer Res
A proposed new international TNM staging system for malignant pleural mesothelioma from the International Mesothelioma Interest Group
Lung Cancer
The importance of surgical staging in the treatment of malignant pleural mesothelioma
J Thorac Cardiovasc Surg
Clinical presentation and natural history of benign and malignant mesothelioma
Semin Oncol
Malignant mesothelioma of the pleura: review of 123 patients
Cancer
Diffuse malignant mesothelioma. Prospective evaluation of 69 patients
Ann Intern Med
Malignant pleural mesothelioma: a survival study
J Surg Oncol
Malignant mesothelioma of the pleura: clinical aspects and symptomatic treatment
Eur J Respir Dis
Diffuse malignant mesothelioma of the pleura in Ontario and Quebec: a retrospective study of 332 patients
J Clin Oncol
Pleuropneumonectomy in the management of diffuse malignant mesothelioma of the pleura. Experience with 29 patients
Thorax
Indications for pneumonectomy. Extrapleural pneumonectomy
Chest Surg Clin North Am
Therapeutic options in malignant mesothelioma
Curr Opin Oncol
Laparoscopy: an important tool in the staging of malignant pleural mesothelioma
Ann Surg Oncol
Chemotherapy in malignant mesothelioma: a review
Cancer Chemother Pharmacol
Chemotherapy in malignant pleural mesothelioma. A review
J Clin Oncol
Chemotherapy for malignant mesothelioma
Semin Thorac Cardiovasc Surg
Statement on malignant mesothelioma in the United Kingdom
Thorax
Malignant mesothelioma: predictors of prognosis and clinical trials
Thorax
In vitro sensitivity of normal human mesothelial and malignant mesothelioma cell lines to four new chemotherapeutic agents
Anticancer Drugs
Randomized phase II trial of cisplatin with mitomycin or doxorubicin for malignant mesothelioma by the Cancer and Leukemia Group B
J Clin Oncol
Phase II trial of topotecan for the treatment of mesothelioma
Am J Clin Oncol
Cited by (23)
Induction chemotherapy, extrapleural pneumonectomy (EPP) and adjuvant hemi-thoracic radiation in malignant pleural mesothelioma (MPM): Feasibility and results
2007, Lung CancerCitation Excerpt :Malignant pleural mesothelioma (MPM) is a relatively rare tumour that is characterized by locally aggressive behaviour which leads to a fatal prognosis mostly due to relative chemo- and radio-resistance and to the difficulty in obtaining a radical excision with surgery. The management of MPM remains controversial and its treatment modalities have yielded poor results: single therapy like chemotherapy, surgery or radiotherapy have not led to improvements in terms of prolonged disease control [1]. Multimodality therapies adopting a combination of surgical resection and adjuvant treatments (chemotherapy, radiotherapy or both) seem to be a better therapeutic option, though only a select group of patients benefits from such treatment [2–5].
Malignant pleural mesothelioma: Overview of the North American and European experience
2004, Thoracic Surgery ClinicsMalignant pleural mesothelioma
2004, Current Problems in CancerIntegration of multimodality approaches in the management of malignant pleural mesothelioma
2004, Clinical Lung Cancer