The Value of Pemetrexed for the Treatment of Malignant Pleural Mesothelioma: A Comprehensive Review

M.Sc., VU University Medical Center, Department of Clinical Pharmacology and Pharmacy, De Boelelaan 1117, 1081 HV Amsterdam, the Netherlands. .
Anticancer research (Impact Factor: 1.83). 09/2013; 33(9):3553-61.
Source: PubMed


This review aims to provide insight into treatment of malignant pleural mesothelioma (MPM) considering effects on survival, quality of life (QoL) and costs, in order to determine the value of pemetrexed in MPM treatment. Cisplatin in combination with pemetrexed or raltitrexed increased survival in MPM, whereas vinorelbine and gemcitabine have led to good response rates. None of these appear to have any detrimental effect with respect to symptoms and global QoL. The cost-effectiveness of pemetrexed-cisplatin was found to be acceptable in advanced MPM compared with cisplatin, but raltitrexed-cisplatin was found to be a more cost-effective treatment option. This may also apply for gemcitabine and vinorelbine, since in contrast to pemetrexed, both agents can be obtained from generic manufacturers. As yet platinum-doublet therapy is the most effective palliative treatment of MPM. To provide a more cost-effective treatment approach for advanced MPM, further research should include randomized controlled trials comparing the recommended pemetrexed-cisplatin directly with platinum doublets with raltitrexed, gemcitabine, or vinorelbine.

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Available from: Christel C.L.M. Boons
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    • "Given the modest survival benefit, the focus of treatment remains palliative with an emphasis on preserving quality of life. Trial data examining the impact of chemotherapy on healthrelated quality of life (HRQoL) is limited (Boons et al, 2013). Where HRQoL has been formally assessed, some studies do report an improvement in disease-specific symptoms (e.g., dyspnoea) (Bottomley et al, 2006). "
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    ABSTRACT: The effect of chemotherapy on health-related quality of life (HRQoL) in malignant pleural mesothelioma (MPM) is poorly understood. Patient-individualised prognostication and prediction of treatment response from chemotherapy is useful but little evidence exists to guide practice. Consecutive patients with MPM who were fit for first-line chemotherapy with pemetrexed and cisplatin\carboplatin were recruited and followed up for a minimum of 12 months. This study focussed on the HRQoL outcomes of these patients using the EQ-5D, EORTC QLQ-C30 and LC13. Seventy-three patients were recruited of which 58 received chemotherapy and 15 opted for best supportive care (BSC). Compliance with HRQoL questionnaires was 98% at baseline. The chemotherapy group maintained HRQoL compared with the BSC group whose overall HRQoL fell (P=0.006) with worsening dyspnoea and pain. The impact of chemotherapy was irrespective of histological subtype although those with non-epithelioid disease had worse HRQoL at later time points (P=0.012). Additionally, those with a falling mesothelin or improvement on modified-RECIST CT at early follow-up had a better HRQoL at 16 weeks. HRQoL was maintained following chemotherapy compared with a self-selected BSC group. Once chemotherapy is initiated, a falling mesothelin or improved RECIST CT findings infer a quality-of-life advantage.British Journal of Cancer advance online publication, 10 March 2015; doi:10.1038/bjc.2015.77
    Full-text · Article · Mar 2015 · British Journal of Cancer
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    • "When compared with methotrexate, a drug widely used in the treatment of osteosarcoma, pemetrexed is polyglutamated by folylpolyglutamate synthase at 90 to 200 times greater efficiency (26). A phase II trial has previously demonstrated the efficacy of pemetrexed in soft tissue sarcoma (27), and pemetrexed has also been shown to exert broad-spectrum effects in numerous types of solid tumor (28–30). Pemetrexed has a wider range of activity than methotrexate, the corresponding antifolate predecessor, as pemetrexed exerts effects on multiple targets, and has the ability to affect purine and pyrimidine synthesis (31). "
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    ABSTRACT: The prognosis for patients with relapsed/metastatic osteosarcoma is poor and the optimal treatment strategy remains to be refined. Whilst gemcitabine plus docetaxel combination treatment has already been demonstrated to have certain promising results in the treatment of osteosarcoma, the use of pemetrexed, a multi-targeted antifolate, remains controversial. In the present study, a retrospective investigation was conducted to evaluate the toxicity and efficacy of the pemetrexed plus cisplatin combination in relapsed/metastatic osteosarcoma. Comparison of this treatment with that of the gemcitabine plus docetaxel combination was also conducted. Clinical data from 39 patients suffering from refractory/metastatic osteosarcoma between January 2005 and May 2011 were reviewed retrospectively. Of these patients, 21 were administered the gemcitabine plus docetaxel combination, and 18 were provided the pemetrexed plus cisplatin combination. Treatment was continued until the occurrence of disease progression or unacceptable toxicity. In the gemcitabine plus docetaxel group, the overall response rate and disease control rate were found to be 9.5 and 28.5% respectively, compared with 5.5 and 33.3% respectively in the pemetrexed plus cisplatin group. The median progression-free survival (PFS) time was found to be 1.8 months for both the gemcitabine plus docetaxel and pemetrexed plus cisplatin groups. The median overall survival (OS) time was 6 months in the gemcitabine plus docetaxel group and 7 months in the pemetrexed plus cisplatin group. No statistically significant differences were recognized between the overall response rates, disease control rates, PFS times and OS times in the two groups. The two combinations appeared to be well tolerated. However, the incidence of grade 3/4 thrombocytopenia and leucopenia was higher in the gemcitabine plus docetaxel group than in the pemetrexed plus cisplatin group. The present study clearly demonstrated that both chemo-combinations were well-tolerated and exerted antitumor activity in patients with refractory/metastatic osteosarcoma. However, with regard to grade 3/4 toxicity, the pemetrexed plus cisplatin chemotherapy appears to be better tolerated.
    Full-text · Article · Nov 2014 · Oncology letters
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    ABSTRACT: Pemetrexed, a new multitarget antifolate antineoplastic agent, has significantly improved the overall survival in nonsquamous non-small-cell lung cancer patients. Presently, pemetrexed is recommended for first line treatment in combination with platinum derivatives, for second line treatment as a single agent and, more recently, as maintenance treatment after first line chemotherapy. In this article we critically appraise the status of pemetrexed including pharmacodynamics, pharmacokinetics, toxicity, and the cost effectiveness of pemetrexed, as well as the predictive biomarkers for pemetrexed based chemotherapy.
    Full-text · Article · Jun 2014 · OncoTargets and Therapy
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