Brief Note on Chemotherapy for Malignant Pleural Mesothelioma

In this article, we will discuss Brief Note on Chemotherapy for Malignant Pleural Mesothelioma. So, let’s get started.

Chemotherapy

Chemotherapy is recommended as part of a multimodality regimen for patients with medically operable MPM. Patients with medically operable stage I to IIIA MPM can receive chemotherapy either before or after surgery. Chemotherapy alone is recommended for patients with stage IIIB or IV MPM (PS 0-2), medically inoperable stages I to IV MPM, or those who refuse surgery. Pemetrexed-based chemotherapy can also be used for malignant peritoneal mesothelioma, pericardial mesothelioma, end tunica vaginalis testis mesothelioma. Trimodality therapy-using chemotherapy, surgery, and hemithoracic RT-has been used in patients with MPM. Median survival of up to 20 to 29 months has been reported for patients who complete trimodality therapy. Nodal status and response to chemotherapy can affect survival. In patients who do not receive induction chemotherapy before EPP, postoperative sequential chemotherapy with hemithoracic RT is recommended. Intraoperative adjuvant therapies—such as hyperthermic pleural lavage, photodynamic therapy, or heated chemotherapy-have also been studied.

First-Line Therapy

A combined first-line regimen using cisplatin/pemetrexed is currently the
only regimen approved by the FDA. A phase 3 randomized trial assessed cisplatin/pemetrexed versus cisplatin alone in patients who were not candidates for surgery; the combined regimen increased survival by 2.8 months when compared with cisplatin alone (12.1 vs. 9.3 months, P=02). Based on this trial and the FDA approval, the NCCN Panel recommends cisplatin/pemetrexed (category 1) for patients with MPM. A
multicenter phase 3 randomized trial (IFCT-GFPC-0701 MAPS) compared adding bevacizumab to cisplatin/pemetrexed (with maintenance bevacizumab) versus cisplatin/pemetrexed alone for patients with unresectable MPM and PS 0 to 2 who did not have bleeding or thrombosis. Overall survival was increased in the bevacizumab plus chemotherapy arm by 2.7 months when compared with chemotherapy alone (18.8 vs. 16.1 months; HR = 0.77; P=.0167). Grade 3 to 4 adverse events were reported in 71% (158/222) of patients receiving the bevacizumab regimen when compared with 62% (139/224) of those receiving cisplatin/pemetrexed alone. More grade 3 or higher hypertension (23% vs. 0%), grade 3 proteinuria (3.1% vs. 0%), and grade 3 to 4 thrombotic events (6% vs. 1%) were observed in patients receiving the
triplet arm. The NCCN Panel recommends (category 1) bevacizumab, cisplatin, and pemetrexed followed by maintenance bevacizumab for bevacizumab-eligible patients with unresectable MPM based on this trial. Contraindications to bevacizumab include uncontrolled hypertension, risk for bleeding or clotting, and substantial cardiovascular morbidity.

Other acceptable first-line combination chemotherapy optionsrecommended by NCCN include: 1) pemetrexed/carboplatin, which was assessed in 3 large phase 2 studies (median survival = 12.7, 14, and 14 months, respectively); or 2) gemcitabine/cisplatin, which was also assessed in phase 2 studies (median survival = 9.6-11.2 months). Gemcitabine/cisplatin may be useful for patients who cannot take pemetrexed. A comparison of 1704 patients with medically inoperable MPM treated with cisplatin/pemetrexed or carboplatin pemetrexed as part of an expanded access trial found that outcomes with the regimens were similar. Recently, the NCCN Panel deleted the caveat that carboplatin/pemetrexed regimen is a better choice for patients with poor PS and/or comorbidities, because panel members feel this regimen can also be used for patients with good PS based on clinical trial data.

A phase 2 trial assessed adding bevacizumab to carboplatin/pemetrexed with or without maintenance bevacizumab as first-line therapy for patients with unresectable MPM. Overall survival was 15.3 months; 34% (26/76) of patients had a partial response and 58% (44/76) had stable disease. Bowel perforation occurred in 4% of patients, and grade 3 to 4 fatigue occurred in 8%; there were 3 toxic deaths. Maintenance bevacizumab
(maximum, 1 year) was administered to patients without progression and/or severe toxicities. The NCCN Panel recommends (category 2A) adding bevacizumab to carboplatin pemetrexed with or without maintenance bevacizumab as a first-line therapy option for patients with unresectable MPM based on this trial. Acceptable first-line single-agent options include pemetrexed or vinorelbine for patients who are not candidates for platinum-based combination therapy.

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