Activity of chemotherapy and immunotherapy on malignant mesothelioma: a systematic review of the literature with meta-analysis
Introduction
Malignant mesothelioma is an infrequent tumor but its incidence is rising. It accounts for around 1500 deaths per year in the United States [1]. Wagner et al. [2] observed the relationship between exposure to asbestos and development of this type of cancer in 1960 and its incidence is expected to increase in the future due to the widespread use of this carcinogen, as observed in Australia [3]. The latency period between asbestos exposure and development of malignant mesothelioma can be as high as 30 years or more [1]. Malignant mesothelioma progresses generally locally, causing death by progressive respiratory failure or intestinal obstruction in the majority of the cases [4].
Long-term survivors are unfrequent [5]. Surgical pleurectomy or extrapleural pneumonectomy are rarely curative. Only a minority of the patients are eligible for these treatments [6], whose mortality and morbidity can be considerable. The efficacy of radiotherapy is not proven [1]. Several chemotherapeutic agents have been tested. Numerous studies are made of case-reports or are retrospective and their significance is weak. The majority of the published prospective trials are non-randomised phase II studies. Recent reviews [1], [7] have pointed out some potentially useful agents: platinum compounds, anthracyclins, high dose methotrexate, alkylating agents and mitomycin C. The response rate to single-agent chemotherapy rarely exceeds 20%. The superiority of polychemotherapy over single-agent therapy is not proven [7]. Some favorable effects have been reported with intrapleural administration of biological response modifiers [7].
The aims of the present study were to assess the methodological quality of publications relative to chemotherapy or immunotherapy in malignant mesothelioma and to aggregate, for trials having a similar methodology, the response rates in order to identify the most active chemotherapeutic drugs and regimens, which could be selected for future randomised trials. For this purpose, we have used the methodological evaluation scale of the European Lung Cancer Working Party (ELCWP) previously published [8] but adapted to the specific design of phase II studies [9].
Section snippets
Material and methods
The search for prospective published trials relative to the treatment of malignant mesothelioma of pleural or peritoneal origin was performed by consulting the Medline, Health Star and National Cancer Institutes electronic data bases and completed by references found in the papers, in textbooks, in reviews and those known by the investigators.
The criteria of eligibility of the articles were the following: to focus only on patients with malignant mesothelioma; to be related to the study of
Trials characteristics
Eighty-three articles, published between 1983 and June 2001, met our selection criteria and were eligible for the analysis. Out of these 83 eligible studies, 80 were single arm phase II trials and three were randomised phase II trials. For the purpose of this review, each arm of the randomised studies was assessed as an independent trial. In two papers, two separate phase II trials were reported in the same publication. Thus, 88 ‘arms’, each considered as an independent study, were analysed.
Discussion
The systematic review that we performed on the medical treatment of malignant mesothelioma and in which we incorporated a quality assessment of the trials suggests that, in term of tumoral activity, the best regimen is the combination of cisplatin and doxorubicin with an overall objective response rate of 28%. Cisplatin containing regimen without doxorubicin, with a 23% objective response rate, is less active than the combination of the two drugs but remains significantly more active than the
References (96)
- et al.
Extrapleural pneumonectomy, chemotherapy and radiotherapy in the treatment of diffuse malignant pleural mesothelioma
J. Thorac. Cardiovasc. Surg.
(1991) - et al.
A review of chemotherapy trials for malignant mesothelioma
Chest
(1998) - et al.
Maintenance chemotherapy for small cell lung cancer: a critical review of the literature
Lung Cancer
(1998) The determination of the number of patients required in a preliminary and follow-up trial of a new chemotherapeutic agent
J. Chron. Dis.
(1961)- et al.
Weekly high-dose cisplatin in malignant pleural mesothelioma
Ann. Oncol.
(1994) - 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.
Combination chemotherapy with cisplatin-vinblastine in malignant mesothelioma
Lung Cancer
(1994) - et al.
Good symptom relief with palliative MVP (mitomycin-C, vinblastine and cisplatin) chemotherapy in malignant mesothelioma
Ann. Oncol.
(1998) - et al.
Cisplatin, mitomycin, and interferon-α2a combination chemotherapy in the treatment of diffuse malignant pleural mesothelioma
Chest
(1999) - et al.
Higher doses of α-interferon do not increase the activity of the weekly cisplatin-interferon combination in advanced malignant mesothelioma
Eur. J. Cancer
(1997)
Weekly systemic combination of cisplatin and interferon α2a in diffuse malignant pleural mesothelioma
Lung Cancer
A phase II trial of dose-escalated doxorubicin and ifosfamide/mesna in patients with malignant mesothelioma
Ann. Oncol.
A phase II trial of ifosfamide/mesna with doxorubicin for malignant mesothelioma
Eur. J. Cancer Clin. Oncol.
Caelyx in malignant mesothelioma: a phase II EORTC study
Ann. Oncol.
Treatment of malignant mesothelioma with epirubicin and ifosfamide: a phase II cooperative study
Ann. Oncol.
Phase II trial of liposomal daunorubicin in malignant pleural mesothelioma
Ann. Oncol.
Mitoxantrone in malignant pleural mesothelioma: a study by the EORTC Lung Cancer Cooperative Group
Eur. J. Cancer
Two dose levels of ifosfamide in malignant mesothelioma
Lung Cancer
Etoposide in malignant pleural mesothelioma: two phase II trials of the EORTC Lung Cancer Cooperative Group
Eur. J. Cancer
Oral etoposide in the treatment of malignant mesothelioma. A phase II study
Ann. Oncol.
Gemcitabine for malignant mesothelioma: a phase II trial by the Cancer and Leukemia Group B
Lung Cancer
High-dose paclitaxel plus G-CSF for malignant mesothelioma: CALGB phase II study 9234
Ann. Oncol.
Palliative and therapeutic activity of IL-2 immunotherapy in unresectable malignant pleural mesothelioma with pleural effusion. Results of a phase II study on 31 consecutive patients
Lung Cancer
A phase II study of combined intravenous and subcutaneous interleukin-2 in malignant pleural mesothelioma
Lung Cancer
Do authors of review articles use systematic methods to identify, assess and synthesize information?
Ann. Oncol.
Chemotherapy in malignant pleural mesothelioma. A review
J. Clin. Oncol.
Diffuse pleural mesothelioma and asbestos exposure in the North Western Cape Province
Br. J. Ind. Med.
Clinical aspects of malignant mesothelioma in Australia
Aust. N.Z. J. Med.
Trimetrexate in malignant mesothelioma: a Cancer and Leukemia Group B phase II study
J. Clin. Oncol.
Benign and malignant mesothelioma
Phase II and III studies with new drugs for non-small cell lung cancer: a systematic review of the literature with a methodology quality assessment
Anticancer Res.
A randomized trial comparing induction chemotherapy versus induction chemotherapy followed by maintenance in small cell lung cancer
J. Clin. Oncol.
Cisplatin administered by the intracavitary route as treatment for malignant mesothelioma
Cancer
A phase II evaluation of cisplatin in unresectable diffuse malignant mesothelioma: a Southwest Oncology Group Study
Invest. New Drugs
Phase II trial of high-dose cisplatin in patients with malignant mesothelioma
Cancer Treat. Rep.
A phase II study of VP-l6 and cisplatin in patients with unresectable malignant mesothelioma. an NCI Canada Clinical Trials Group Study
Invest. New Drugs
Results of a phase II trial of combined chemotherapy for patients with diffuse malignant mesothelioma of the pleura
Cancer
Randomized phase II trial of cisplatin with mitomycin or doxorubicin for malignant mesothelioma by the Cancer and Leukemia Group B
J. Clin. Oncol.
Treatment of malignant pleural mesothelioma with cisplatin, mitomycin C and alpha interferon
Oncology
Combined chemotherapy in pleurectomized malignant pleural mesothelioma patients
J. Chemother.
A phase II trial investigating primary immunochemotherapy for malignant pleural mesothelioma and the feasibility of adjuvant immunochemotherapy after maximal cytoreduction
Ann. Surg. Oncol.
Combined systemic chemoimmunotherapy in advanced diffuse malignant mesothelioma: report of a phase I-II study of weekly cisplatin/interferon alpha-2a
J. Clin. Oncol.
Dihydro-5-azacytidine and cisplatin in the treatment of malignant mesothelioma. A phase II study by the Cancer and Leukemia Group B
Cancer
Cisplatin and gemcitabine treatment for malignant mesothelioma: a phase II study
J. Clin. Oncol.
Cisplatin in combination with irinotecan in the treatment of patients with malignant pleural mesothelioma. A pilot phase II clinical trial and pharmacokinetic profile
Cancer
Interferon alpha and doxorubicin in malignant mesothelioma: a phase II study
Aust. N.Z. J. Med.
Randomized comparison of cyclophosphamide, imidazole carboxamide, and adriamycin versus cyclophosphamide and adriamycin in patients with advanced stage malignant mesothelioma: a Sarcoma Intergroup Study
J. Clin. Oncol.
Randomized trial of doxorubicin versus cyclophosphamide in diffuse malignant pleural mesothelioma
Cancer Treat. Rep.
Cited by (185)
Peritoneal mesothelioma: PSOGI/EURACAN clinical practice guidelines for diagnosis, treatment and follow-up
2021, European Journal of Surgical OncologyCitation Excerpt :Before the Vogelzang et al.’s randomized trial in pleural mesothelioma patients, many protocols were used [54]. In an exhaustive review with meta-analysis, Berghmans et al. compiled results from different SC protocols in pleural and peritoneal mesothelioma [42]. Four groups were compared: cisplatin without doxorubicin (20 trials); doxorubicin without cisplatin (8 trials); combination of cisplatin and doxorubicin (6 trials), and regimens without cisplatin or doxorubicin (54 trials).
The Treatment of Malignant Pleural Mesothelioma: From the Current Standard to Novel Possible Therapeutic Strategies
2019, Malignant Pleural Mesothelioma: A Guide for CliniciansPeritoneal Mesothelioma: Systematic Review of Hyperthermic Intraperitoneal Chemotherapy (HIPEC) Protocol Outcomes
2023, Indian Journal of Surgical OncologyExtrapelvic Endometriosis Mimicking Peritoneal Surface Malignancy: Case Report and a Review of Literature
2023, Indian Journal of Surgical Oncology