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.
Pemetrexed disodium was approved by the US Food and Drug Administration (FDA) to treat patients with malignant pleural mesothelioma in unresectable disease and those who are not candidates for curative surgery. Several trials from a combination drug to therapy with pemetrexed have been performed. Hughes et al showed a 32% response rate using pemetrexed 500 mg/m2 and carboplatin (area under the curve [AUC] of 5) on an every-21-day schedule.  An interesting combination of drugs, including raltitrexed and oxaliplatin, has shown a response rate of 20% in previously treated patients.
Antineoplastic Agents, Other
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 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.
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 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.
Ranpirnase is a designated orphan drug for treatment of malignant mesothelioma. It has been shown in vitro and in vivo to target tumor cells while sparing normal cells. The drug is internalized by endocytosis and released into cancerous cell cytosol, where selective ribosomal RNA (rRNA) degradation occurs. Ranpirnase therapy results in protein synthesis inhibition, cell cycle proliferation cessation, and apoptosis induction. Ranpirnase is administered in conjunction with doxorubicin.
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.
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