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In a new study, researchers found a neoadjuvant application of RAPTA-T, a metal-based compound, can enhance the efficacy of cisplatin, a standard mesothelioma chemotherapy, for pleural mesothelioma patients.
Studies over the years have found that in many instances, chemotherapy on its own has a low success rate in treating mesothelioma. Despite limited success, the standard of care for pleural mesothelioma has long been considered a combination chemotherapy treatment of pemetrexed and cisplatin. Various reports have only seen a median survival of about 12 months, with a little over 5 months of survival before disease progression. These limitations have led researchers to try to identify newer treatment combinations that can improve the efficacy of this standard of care.
This clinical trial explored if another metal-based therapy could improve the effect of platinum-based cisplatin. The researchers noted the limits of chemotherapy alone may be due to the inability to sufficiently distribute the treatment to tumors because solid tumors have an abnormal structure of blood vessels and often create a high pressure of interstitial fluids (fluid that surrounds cells). These conditions make it difficult for the chemotherapy to travel effectively throughout the tumors.
With this in mind, researchers wanted to explore if a new class of metal-based drugs called RAPTA could complement cisplatin and improve success rates. Previous preclinical trials had shown RAPTA drugs could inhibit primary tumor growth and prevent metastasis, while also offering a low toxicity that yields fewer side effects than standard chemotherapy.
In a lab setting, the researchers found a low dose of RAPA-T combined with cisplatin as a first-line treatment enabled higher chemotherapy uptake by the tumors, as well as inhibited PARP-1, a nuclear protein that allows for angiogenesis (development of new blood cells) and DNA damage repair. Research has associated high expression of this protein as an indicator of poor prognosis and treatment resistance in tumors. PARP-1 inhibitors decrease the endothelial growth factor in tumors, meaning tumors were more responsive to treatment and less likely to metastasize.
Overall, the study showed RAPTA-T in combination with cisplatin could create a better antitumor effect than chemotherapy on its own. The researchers noted the treatment could be used palliatively for advanced mesothelioma, and as a neoadjuvant treatment for resectable mesothelioma. With such promising findings, this early phase trial gave researchers hope that RAPTA-T could become part of a first-line treatment for mesothelioma in the future with further study.