Malignant peritoneal mesothelioma (MPM) is a rare tumoral disease characterized by the diffuse involvement of the peritoneal serosa. The incidence of all mesotheliomas is estimated quite differently in various reports with the highest rates in industrialized countries. In France, the estimated incidence is 300 cases/year. Three types of malignant mesotheliomas are described in the WHO classification: epithelioid, sarcomatoid and biphasic.~The standard treatment of MPM is surgery. It has been shown that cytoreductive surgery (CRS) associated to hyperthermic intraperitoneal chemotherapy (HIPEC) improves prognosis resulting in a median overall survival of 29.5 months to 53 months and an 5 years overall survival rate ranging between 39 to 63%. Cytoreductive surgery should be complete or almost complete (CCR0/1) as macroscopic residual disease deteriorates prognosis.~However some patients are not eligible for surgery due to the locoregional extension of the disease. Although debulking surgery may still be considered, its results are less encouraging than CRS and HIPEC.~The neoadjuvant treatment combining Cisplatin and Pemetrexed became a routinely applied option for initially unresectable patients after the publication of an open-label study inspired by previous results of a randomized trial in pleural mesothelioma. This study showed a benefit in median survival of 5 months and an increase in the response rate of 10%. Ever since, other phase II studies were proposed but their benefit is still limited. Pleural mesothelioma which is more common and represents the model of choice for the treatment of peritoneal mesothelioma has also benefitted from phase III studies analyzing the addition of a targeted therapy (Bevacizumab) and phase II trials proposing immunotherapy.~By contrast, peritoneal mesothelioma was the setting of choice for testing intraperitoneal administration of chemotherapy either as early postoperative intraperitoneal chemotherapy (EPIC) or as neoadjuvant intraperitoneal chemotherapy. Both studies offered promising results showing a sensitivity of MPM to intraperitoneal administration.~Pressurized IntraPeritoneal Aerosol Chemotherapy (PIPAC) has recently been developed and shows interesting results in the neoadjuvant context of several peritoneal carcinomatoses while producing little toxicity. PIPAC is a modality of repeated administration of intraperitoneal chemotherapy during laparoscopy using aerosols at the pressure of the capnoperitoneum (12mmHg). Data from ex-vivo, in-vivo and human studies demonstrated a higher local drug bioavailability when compared to liquid IP chemotherapy. PIPAC was tested in the setting of malignant mesothelioma showing encouraging results.~In our study MESOTIP, patients in the experimental arm will be treated by 4 PIPAC (Cisplatine+Doxorubicine) alternating with 6 cycles of standard intravenous chemotherapy (Cisplatine+Pemetrexed).~Although retrospective reports showing the interest of PIPAC in the neoadjuvant setting for different peritoneal carcinomatosis origins were published, MESOTIP would be the first study to combine PIPAC to systemic chemotherapy in the first-line of treatment and to only include patients not eligible for surgical treatment and proposing a complete cytoreductive surgery associated to HIPEC for patients converted to resectability.~MESOTIP aim to show an improvement of the overall survival in the experimental arm.
MESOTIP is a randomized trial evaluating the association of PIPAC and systemic chemotherapy versus systemic chemotherapy alone as 1st-line treatment of Malignant Peritoneal Mesothelioma In this study, patients in the experimental arm will be treated by 4 PIPAC (Cisplatine+Doxorubicine) alternating with 6 cycles of standard intravenous chemotherapy (Cisplatine+Pemetrexed).~MESOTIP aim to show an improvement of the overall survival in the experimental arm.