Medication Summary
Treatment options for the management of malignant mesothelioma include surgery, chemotherapy, radiation, and multimodality treatment. Currently, no therapy is considered standard. The standard methods of surgery, radiation, or chemotherapy alone have not improved survival. At present, the first choice for treatment of metastatic malignant pleural mesothelioma is the combination of ipilimumab and nivolumab.
Pemetrexed disodium is approved by the US Food and Drug Administration (FDA) for the treatment of malignant pleural mesothelioma in patients who have unresectable disease and those who are not candidates for curative surgery. Nivolumab in combination with ipilimumab is FDA-approved for first-line treatment of unresectable malignant pleural mesothelioma. [38]
Antineoplastic Agents, Other
Class Summary
These agents interfere with cell reproduction. Some agents are cell-cycle specific, while others (eg, alkylating agents, anthracyclines, cisplatin) are not phase specific. Cellular apoptosis is also a potential mechanism of many antineoplastic agents.
Gemcitabine (Gemzar)
Gemcitabine is a cytidine analogue that, after being metabolized intracellularly to an active nucleotide, inhibits ribonucleotide reductase and competes with deoxycytidine triphosphate for incorporation into deoxyribonucleic acid (DNA). It is cell-cycle specific for the S phase.
Pemetrexed disodium (Alimta)
This agent disrupts folate-dependent metabolic processes essential for cell replication. It specifically inhibits thymidylate synthase (TS), dihydrofolate reductase (DHFR), and glycinamide ribonucleotide formyltransferase (GARFT), which are folate-dependent enzymes involved in de novo biosynthesis of thymidine and purine nucleotides. Pemetrexed disodium is indicated for use in combination with cisplatin to treat patients with malignant pleural mesothelioma in unresectable disease, as well as patients who are not candidates for curative surgery.
Cisplatin (Platinol)
Cisplatin is a platinum-based alkylating agent. It inhibits DNA synthesis and, thus, cell proliferation by causing DNA crosslinks and denaturation of the double helix. Cisplatin is indicated for use in combination with pemetrexed disodium to treat patients with malignant pleural mesothelioma in unresectable disease and those who are not candidates for curative surgery.
Doxorubicin (Adriamycin)
Doxorubicin is an anthracycline antibiotic that causes DNA strand breakage through effects on topoisomerase II and direct intercalation into DNA, which causes DNA polymerase inhibition. This drug is both mutagenic and carcinogenic.
Antineoplastics, Monoclonal Antibody
Nivolumab (Opdivo)
Nivolumab is a monoclonal antibody to programmed cell death-1 protein (PD-1). It blocks the interaction between PD-1 and its ligands, PD-L1 and PD-L2. Combination therapy with ipilimumab is indicated for first-line treatment of adults with unresectable malignant pleural mesothelioma.
Ipilimumab (Yervoy)
Ipilimumab is a targeted a recombinant, human cytotoxic T-lymphocyte antigen 4 (CTLA-4)–blocking antibody. It binds to CTLA-4 and blocks the interaction of CTLA-4 with its ligands, CD80/CD86. Blockade of CTLA-4 augments T-cell activation and proliferation. The proposed mechanism of action is indirect, possibly through T-cell–mediated antitumor immune responses. Combination therapy with nivolumab is indicated for first-line treatment of adults with unresectable malignant pleural mesothelioma.
Bevacizumab (Avastin)
Recombinant humanized monoclonal antibody to VEGF; blocks the angiogenic molecule VEGF thereby inhibiting tumor angiogenesis, starving tumor of blood and nutrients. Bevacizumab has orphan drug designation for treatment of mesothelioma.
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Positron emission tomography (PET) scan in a male patient with known mesothelioma. Although PET scanning is not standard for the evaluation of mesothelioma, this image illustrates the extent of the disease into the mediastinum and peritoneum.
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Chest radiograph of a 58-year-old patient with mesothelioma and shortness of breath. This image reveals diffuse, left-sided pleural thickening, a pleural effusion, and ipsilateral volume loss.
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Computed tomography scan of a 58-year-old patient with mesothelioma and shortness of breath. This image shows the extensive pleural thickening that is characteristic of mesothelioma, effusion, and reduction in the volume of the affected hemithorax.
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Computed tomography scan of the chest. This image demonstrates mesothelioma that extends into the chest wall. Note the concentric left pleural thickening, pleural effusion, reduction in volume of the left hemithorax, and the tumor nodules within the chest wall.
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Magnetic resonance imaging (MRI) scan in a 72-year-old Veterans Administration patient with left-sided mesothelioma. Note that the MRI scan well delineates the soft tissues and, in particular, the thoracoabdominal interface at the diaphragm.
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Computed tomography (CT) scan in a male Veterans Administration patient with a history of asbestos exposure and an enlarging abdominal girth. This upper CT scan slice reveals the calcified pleural plaques along the diaphragmatic surface that are associated with asbestos exposure. Ascites is seen lateral to the liver. Aspiration of the ascitic fluid demonstrated mesothelioma.
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The soft-tissue window setting of this chest computed tomography (CT) scan shows the envelope-like mass along the pleural surface surrounding the lung. This was a mesothelioma.
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The classic description of malignant pleural mesothelioma is a thickening in the pleural space with encasement of the lung by a rindlike visceral pleura. These gross specimens are from an autopsy lung case with diffuse thickening of the pleura causing compression of the underlying lung tissue.
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This histologic section stained with hematoxylin and eosin shows papillary structures on the right and a transition to a more solid pattern on the left.
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A solid pattern of mesothelioma on the right of this histologic section transitions to a spindle cell morphology on the left of the image in this predominantly sarcomatoid malignant mesothelioma.
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Well differentiated papillary mesothelioma is characterized with a single layer of bland cuboidal cells lining fibrovascular cores, as demonstrated in this image.
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Immunohistochemistry helps to demonstrate that the atypical mesothelial cells in this reactive proliferation are in fact in one roughly linear layer, an important criterion supporting a benign process.
