**2.5 Conclusions**

*Mesothelioma*

Gefitinib and erlotinib, which are tyrosine kinase inhibitors, acting on the epidermal growth factor receptor (EGFR), have been shown to have no significant action in MPM. By contrast, angiokinase inhibitors (nintedanib) acting on VEGF receptors, platelet-derived-growth factors, fibroblastic growth factors, and Src and Abl kinase signaling improved progression-free survival in patients with MPM

Bevacizumab, which is an anti-VEGF antibody [38] in combination with cisplatin

and pemetrexed, significantly increased overall survival in patients with MPM. Immune checkpoint inhibitors such as anti-CTLA 4 (tremelimumab and iplimumab)

and anti-PD1 antibodies (avelumab and durvalumab) are under investigation.

The recommendations discussed at the Washington DC 2016 meeting by the Peritoneal Surface Oncology Group International (PSOGI) regarding therapeutic

1.Patients with MPM who are operable will be given CRS and HIPEC. The applied surgical treatment will include peritonectomy procedures (there are still controversies related to parietal peritonectomy: selective parietal peritonectomy vs. complete parietal peritonectomy). During the surgical treatment, it will be taken into account that the preservation of the viscera is preferred and the invaded retroperitoneal lymph nodes will be removed. Optimal cytoreduction will be assessed by validated peritoneal staging scoring systems: CC or R-score, in which the CRS objectives are to achieve a CC-0 or CC-1 score, in which the

HIPEC will be used with cisplatin and carboplatin, either alone or in combination with doxorubicin, pemetrexed, ifosfamide, and mitomycin. Mitomycin has also been used as the only chemotherapeutic agent but with a slight decrease in survival. Normothermic intraperitoneal chemotherapy with pemetrexed and other chemotherapeutic agents has also been used with a slight

2.Patients with well-differentiated papillary and multicystic mesothelioma will be treated with either CRS alone or HIPEC-associated CRS depending on the stage of the disease. The benefit of combining HIPEC therapy is unknown.

3.Patients with biphasic, sarcomatoid, or unresectable PMP will only be treated by systemic chemotherapy. New chemotherapeutic agents are being tested, especially for patients who have seen an increase in Ki67, seen in immunohisto-

4.The contribution of adjuvant chemotherapy to the treatment of patients with PMP is unknown. The study conducted by Sugarbaker and colleagues in 2017 [27] on long-term adjuvant combined intraperitoneal and systemic chemo-

It has been shown in published studies that the response rate of malignant epithelioid mesothelioma to systemic chemotherapy is around 20%. The chemotherapeutic agents used are pemetrexed, carboplatin, cisplatin, and

5.New chemotherapeutic agents such as anti-mesothelin antibody (anetumumab), anti-PDL-1 (pembrolizumab), CAR T cells, and *Listeria*-based immunotherapy

when co-administered with pemetrexed and cisplatin [37].

*2.4.4 Recommendations in the treatment of MPM*

strategies [39] in patients with MPM were the following:

peritoneal nodules have a diameter of less than 2.5 mm.

increase in the survival of patients with MPM.

chemical studies.

bevacizumab.

therapy showed promising results.

can improve the survival of patients with PMP.

**24**

Patients with peritoneal mesothelioma, due to nonspecific symptoms, present in advanced stages of the disease. An important role in determining the histological subtype of peritoneal mesothelioma is played by immunohistochemistry. Multidisciplinary management is preferred for patients with MPM. CRS and HIPEC appear to be the most effective therapeutic modalities in the treatment of MPM. Bidirectional chemotherapy is able to increase the resectability rate in patients with diffuse MPM, initially considered unresectable. Modern therapies such as molecular therapy and immunotherapy can increase the overall survival of patients with MPM. New therapeutic approaches have improved the prognosis only for patients in the early stages of the disease.
