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. 2007 Jan 24;2007(1):CD005574.
doi: 10.1002/14651858.CD005574.pub2.

Pemetrexed disodium in combination with cisplatin versus other cytotoxic agents or supportive care for the treatment of malignant pleural mesothelioma

J Green  1 , Y Dundar, S Dodd, R Dickson, T Walley
Affiliations

Pemetrexed disodium in combination with cisplatin versus other cytotoxic agents or supportive care for the treatment of malignant pleural mesothelioma

J Green et al. Cochrane Database Syst Rev. .

Abstract

Background: Malignant pleural mesothelioma (MPM) is a highly aggressive malignancy whose incidence is expected to increase in the United Kingdom, Western Europe, and Australia over the next 20 years as a result of occupational exposure to asbestos fibres. Surgery is feasible in only a small proportion of cases, and radiotherapy and cytotoxic chemotherapy are used in palliation. Pemetrexed is the first and only chemotherapy agent that has been granted a marketing approval for use in combination with cisplatin for the treatment of chemo-naïve patients with unresectable MPM.

Objectives: To examine evidence on the clinical effectiveness of pemetrexed disodium used in combination with cisplatin for the treatment of unresectable malignant pleural mesothelioma in chemotherapy naïve patients compared with other cytotoxic agents used alone or in combination, or supportive care.

Search strategy: CENTRAL (Issue 2, 2005), EMBASE (1980-2005), MEDLINE (1980-2005), HTA database (1990-2005), Web of Knowledge (1990-2005) and handsearching (including reference lists of retrieved articles and the pharmaceutical company submission to to NICE), up to October 2005.

Selection criteria: Randomised Controlled Trials (RCTs) where the use of pemetrexed disodium in combination with cisplatin is compared with other cytotoxic agents, or supportive care for the treatment of malignant pleural mesothelioma (or non-RCTs, in the absence of RCT data ).

Data collection and analysis: Outcomes included overall survival, tumour response, progression-free survival, toxicity and quality of life. Data extraction and quality assessment of included trials was completed independently. Trial data and quality assessment were tabulated and presented narratively.

Main results: One RCT involving 448 patients and comparing pemetrexed plus cisplatin versus cisplatin alone for the treatment of unresectable malignant mesothelioma was included in the review. In the intention-to-treat study population, the median survival was statistically significantly longer in the combination arm of pemetrexed plus cisplatin when compared with the cisplatin alone arm. (12.1 and 9.3 months, respectively, p=0.002). The incidence of grade 3/4 toxicities was higher in the combination arm compared with the cisplatin alone arm.

Authors' conclusions: Pemetrexed disodium in combination with cisplatin and with folic acid and vitamin B(12 )supplementation may improve survival when used in combination with cisplatin in good performance status patients. Further studies including patients with poor performance status are needed in order to generalise the treatment findings. Further studies are also needed into the optimum chemotherapy, and a clear definition of what constitutes best supportive care.

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Conflict of interest statement

None known.

Update of

References

References to studies included in this review

EMPHACIS {published data only}
    1. Gralla RJ, Hollen PJ, Liepa AM, Symanowski JT, Boyer MJ, Abraham R, et al. Improving quality of life in patients with malignant pleural mesothelioma: results of the randomized pemetrexed + cisplatin vs. cisplatin trial using the LCSS‐Meso instrument. Proceedings of the American Society of Clinical Oncology 2003:621.
    1. Vogelzang NJ, Rusthoven JJ, Symanowski J, Denham C, Kaukel E, Ruffie P, et al. Phase III study of pemetrexed in combination with cisplatin versus cisplatin alone in patients with malignant pleural mesothelioma. J Clin Oncol. 2003; Vol. 21, issue 14:2636‐2644. - PubMed
EMPHACIS 2003 {published data only}
    1. Vogelzang NJ, Rusthoven JJ, Symanowski J, Denham C, Kaukel E, Ruffie P, et al. Phase III study of pemetrexed in combination with cisplatin versus cisplatin alone in patients with malignant pleural mesothelioma. J Clin Oncol 2003;21(14):2636‐2644. - PubMed

References to studies excluded from this review

Adjei {published data only}
    1. Adjei AA, Erlichman C, Sloan JA, Reid JM, Pitot HC, Goldberg RM, et al. Phase I and pharmacologic study of sequences of gemcitabine and the multitargeted antifolate agent in patients with advanced solid tumors. J Clin Oncol 2000;18(8):1748‐1757. - PubMed
Ceresoli {published data only}
    1. Ceresoli GL, Zucali PA, Favaretto A, Marangalo M, Conte G, Ceribelli A, et al. A phase II study of pemetrexed and carboplatin as front‐line chemotherapy in patients with malignant pleural mesothelioma (MPM). American Society of Clinical Oncology (ASCO) Annual Meeting. 2005.
Hughes {published data only}
    1. Hughes A, Calvert P, Azzabi A, Plummer R, Johnson R, Rusthoven J, et al. Phase I clinical and pharmacokinetic study of pemetrexed and carboplatin in patients with malignant pleural mesothelioma. J Clin Oncol 2002;20(16):3533‐3544. - PubMed
Janne {published data only}
    1. Janne PA, Simon GR, Langer RN, Taub RN, FDowlati P, Fidias P, et al. An update of pemetrexed plus gemcitabine as front‐line chemotherapy for patients with malignant pleural mesothelioma (MPM): a phase II clinical trial. ASCO Meeting. 2005:Abstract no: 7067.
Milward {published data only}
    1. Milward M, Clarke S, Beale P, Boyer M, Childs A, Bishop J, et al. Phase I trial of pemetrexed (Alimta) and vinorelbine in patients with advanced cancer. American Society of Clinical Oncology (ASCO) Annual Meeting. 2001.
Scagliotti {published data only}
    1. Scagliotti GV, Shin DM, Kindler HL, Vasconcelles MJ, Keppler U, Manegold C, et al. Phase II study of pemetrexed with and without folic acid and vitamin B12 as front‐line therapy in malignant pleural mesothelioma.. J Clin Oncol 2003;21(8):1556‐1561. - PubMed
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