The Use of Chemotherapy in Patients with Advanced Malignant Pleural Mesothelioma: A Systematic Review and Practice Guideline

Abstract

Background: This clinical practice guideline, based on a systematic review, was developed to determine which chemotherapeutic agents (or combinations of agents) show the highest response rates, improved survival, quality of life, or symptom control in patients with advanced malignant pleural mesothelioma. Methods: A thorough systematic search of the literature was conducted for published articles and conference proceedings for applicable abstracts. Relevant trials, published as articles and abstracts, were selected and assessed. External feedback was obtained from Ontario clinicians, and the guideline was approved by the provincial Lung Cancer Disease Site Group. Results: One hundred nineteen studies were eligible, including eight randomized trials and 111 phase II trials. The pooled response rates from phase II trials suggest that response rates with combination chemotherapy are higher than with single agents. Data from the largest randomized controlled trial demonstrated that chemotherapy with cisplatin and pemetrexed significantly improves response rates (41% versus 17%, p Ͻ 0.001), time to progression (5.7 months versus 3.9 months, p ϭ 0.001), and overall survival (median, 12.1 months versus 9.3 months, hazard ratio ϭ 0.77, p ϭ 0.020) in comparison to single-agent cisplatin. A second trial demonstrated cisplatin and raltitrexed significantly improved median survival compared to single-agent cisplatin (11.4 months versus 8.8 months; hazard ratio ϭ 0.76, p ϭ 0.0483). Overall response rate (24% versus 14%, p ϭ 0.056) was greater in the combination treatment arm, but this difference was not statistically significant. Conclusions: There is good evidence to recommend chemotherapy with pemetrexed and cisplatin for adult patients with symptomatic advanced malignant pleural mesothelioma. Such treatment should be administered with supplementation of vitamin B 12 and folic acid. If pemetrexed is not available, cisplatin plus raltitrexed is a reasonable alternative.

COX-2 specific inhibitors enhance the cytotoxic effects of pemetrexed in mesothelioma cell lines

“…Chemotherapy has been limited to use in palliative therapy of the disease and as an adjunct to radical surgery. A number of cytotoxic compounds have been assessed and typically give tumour response rates in the range of 10-30% when used as single agents [2][3][4]. Combination regimens have been investigated in order to increase the benefit.…”

Use of totally implantable central venous access port via the basilic vein in patients with thoracic malignancies

“…Third-generation monotherapy, as well as new drugs such as amrubicin or pemetrexate, are considered good candidates for second / third-line regimens; 2 in malignant pleural mesothelioma and invasive thymoma, several complex but effective regimens have been reported. 3,4 Therefore, patients with advanced thoracic malignancy frequently require repeated puncture of peripheral veins for blood tests, administration of consecutive chemotherapeutic agents, fl uid administration, and occasionally parenteral nutrition over a long period of time.…”

Contemporary radiation therapy techniques in malignant pleural mesothelioma: a case report

“…Chemotherapy alone is recommended for medically inoperable patients with stages I-IV MPM and in those with sarcomatoid histology. [8,9] Surgery and radiotherapy have a very limited role in the treatment of patients with advanced MPM and chemotherapy is the only potential treatment option for the majority of people diagnosed with mesothelioma. [10] A trimodality therapeutic approach, utilizing chemotherapy, surgery and hemithoracic radiotherapy, has recently been proposed for the treatment of MPM, with good preliminary results.…”