Peritoneal Mesothelioma: A Review

Alessio Bridda, MD, Ilaria Padoan, MD, Roberto Mencarelli, MD, Mauro Frego, MD

Disclosures
In This Article

Treatment

For patients with confirmed MPM, radical resection is associated with better prognoses and should be pursued when possible. Other treatments for peritoneal mesothelioma include intensive loco-regional therapeutic strategies: cytoreductive surgery, hyperthermic intraoperative or early postoperative intraperitoneal chemotherapy, and immunotherapy.

Surgery can achieve a complete or incomplete resection. The aim of cytoreductive surgery is to remove as much tumor as possible, as it is often not possible to achieve a complete resection. After surgical debulking, the resection can be classified according to the Completeness of Cytoreduction Score,[45] which evaluates the residual peritoneal seeding within the operative field: complete (CC-0) or partial with a diameter of the residual nodules < 0.25 cm (CC-1), 0.25-2.5 cm (CC-2), > 2.5 cm or confluence of tumor nodules (CC-3). The CC-1 tumor nodule size is thought to be penetrable by intracavitary chemotherapy and is, therefore, designated as complete cytoreduction if perioperative intraperitoneal chemotherapy is used. The limitation of this score is the fact that it can be evaluated only after surgery; therefore, no preoperative informations can be obtained about the resectability of the tumor. Survival after cytoreductive surgery and intraperitoneal chemotherapy is 35.8 months for patients treated with a CC-0 or CC-1 resection, and only 6.5 months for those treated with a CC-2 or CC-3 resection.[46] Widely used in both noninvasive and invasive peritoneal surface malignancy, the completeness of cytoreduction score is thought to be the principle prognostic indicator.

Chemotherapy has an important role in palliation. It can be administered systemically or directly into the abdomen. The overall response rate reported with a single agent chemotherapy, combined chemotherapy, intraperitoneal chemotherapy, continuous hyperthermic peritoneal perfusion are 13.1%, 20.5%, 47.4%, and 84.6%, respectively.[47] Cisplatin is the most studied agent, with activity in 25% of patients.[18]

Direct exposure of antitumor agent to the peritoneal surface is considered to be most effective against malignant peritoneal mesothelioma. Intraperitoneal chemotherapy can be instilled after surgery or without surgery through an abdominal catheter. Advantages of intraperitoneal chemotherapy include greatly enhanced drug concentrations in the peritoneal cavity and decreased systemic toxicity.

Cytoreductive surgery followed by intraperitoneal hyperthermic perfusion is the standard treatment for resectable tumors at diagnosis. A preheated (42.5 degrees C) perfusate with 2 or 3 antineoplastic agents (cisplatin, mitomycin C, fluorouracil, doxorubicin, and/or paclitaxel) is infused continuously into the closed or semi-closed abdomen after surgery. In a recent Phase II study[48] with cisplatin, mitomycin C and doxorubicin, the major morbidity rate reported was 12%: the most significant complications were anastomotic leaks (11%), abdominal bleeds (1.9%) and sepsis (1.9%). Operative mortality rate was 12%. In another study, after cytoreductive surgery and continuous hyperthermic peritoneal perfusion with cisplatin, fluorouracil, and paclitaxel, peritoneal progression-free and overall survival were reported to be 17 and 92 months, respectively. Deraco and colleagues reported 5-year overall survival, disease-free survival, and progression-free survival of 70%, 63%, and 51% respectively.[49]

Systemic chemotherapy has also been investigated. Pemetrexed in combination with cisplatin has shown survival improvement in patients with pleural mesothelioma. Data from uncontrolled studies suggest similar antineoplastic efficacy in patients with peritoneal mesothelioma,[50,51] and should be the standard of care for patients with unresectable malignant mesothelioma. The disease control rate reported is 71.2%: it includes partial responses or stable disease. No complete responses are reported for this chemotherapy.[52]

Other drug regimens used for unresectable disease are vinorelbine and gemcitabine, either alone or combined with platinum compounds.[51] The response rate of vinorelbine alone is 24%.[53] Irinotecan[54] and gefinitib[55] have not been shown to be effective when used alone.

Immunotherapy is used on an experimental basis, mainly for pleural mesothelioma.[56] Humanized anti-CD3 antibodies (OKT3),[57] cytotoxic T lymphocytes (CTL),[58] interferon alfa-2a,[59] and autovaccine[60] have all been used anecdotally for palliation of advanced peritoneal mesothelioma, but more data are needed before this therapy can be recommended. Radiation therapy has a limited role in peritoneal mesothelioma and it is not currently used.[61]

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