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Malignant pleural mesothelioma (MPM) is a rare cancer commonly associated with asbestos exposure.1 Recently, it was determined that germline mutations in BRCA1-associated protein-1 (BAP1) may predispose to mesothelioma development in nonasbestos-exposed patients.2 Although basic biologic knowledge about MPM has increased during the past decade, and many new potentially active agents have reached various stages of development, the number of novel treatments that have been approved for MPM patients is limited.

The increasing experience of phase II trials assessing the efficacy of surgery-based multimodal treatment of MPM has reached the point where consistent overall survival data ranging between a median survival of 14 and 25.5 months is demonstrated for extrapleural pneumonectomy (EPP).3 To date, combined multimodality treatment is the most commonly used treatment for MPM in many centers. One particular approach involves sequencing the surgery to follow induction chemotherapy—a concept that has been adapted from stage III NSCLC with the idea of downstaging the tumor or eradicating the outer tumor layer for better resectability.4 Further justification for sequencing chemotherapy before surgery is the expectation that the chemotherapy regimen will be better tolerated prior to surgery, and the full required dose will be applied.

General Principles (Technical, Clinical, Oncologic) That Support This Approach (Ease and Efficiency of Care)

Recent reviews5,6 confirm that combined treatment with the antifolate, pemetrexed, and cisplatin achieve best overall survival and quality of life for patients. Therefore, cisplatin plus an antifolate is currently the most frequently used regimen for first line chemotherapy in a neo- or adjuvant setting. The use of induction chemotherapy is supported not only in a response rate of 30% to 40%, but also in convincing resectability rates (up to 74%) for EPP after induction chemotherapy reported in prospective trials.4,7 Unfortunately, clinical assessment of the chemotherapy treatment response is difficult, and the only available tool for measuring this response is the modified RECIST criteria8 which are lacking in reliable reproducibility.9 Therefore, although the exact value of induction chemotherapy may be difficult to assess, the reported outcome after induction chemotherapy followed by EPP described in the following paragraph (MST ranging from 14 to 25.5 months) supports this approach and is definitely not inferior to other multimodal concepts, such as adjuvant chemotherapy after surgery (MST ranging from 13 to 24 months.3 The fact that MPM does not respond very well to chemotherapy in comparison with other malignancies has been confirmed in all neoadjuvant treatment studies. Nevertheless, there are reports of chemotherapy-induced complete pathological responses in the literature.10 However, in our experience of 128 EPP after neoadjuvant chemotherapy with cisplatin/gemcitabine or cisplatin/pemetrexed, we have observed only one complete response to date. The strongest argument for induction versus adjuvant chemotherapy is that chemotherapy is often difficult to administer in the postsurgery period after EPP or P/D, and the necessity of dose reduction is not unusual. Not surprisingly, ...

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