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A phase I clinical trial tested the safety and efficacy of a new chemotherapy combination to be applied as heated intraoperative chemotherapy following surgical resection of pleural mesothelioma. The main goal of the study was to find the maximum safe dosage of chemotherapy drug gemcitabine with cisplatin when applied in this manner. In the past, heated intraoperative chemotherapy for pleural mesothelioma has often only studied cisplatin alone.
The early phase study monitored 104 pleural mesothelioma patients from 2007 to 2011. The researchers noted that the median age of those being treated was 65, and the majority of the patients were male. Based on the average tumor volumes, participants in the study had stage 1 or stage 2 pleural mesothelioma. With more advanced stages, patients would often not be considered eligible for surgical resection, as the mesothelioma cells would have already spread more distantly.
Based on the cell type, the expected disease progression and the individual’s overall health, the researchers determined which surgical procedure would be the best treatment for each individual participant. As a result, 59 patients were treated with an extrapleural pneumonectomy, a more radical surgery that entails removal of the affected lung, lung and heart linings, and part of the diaphragm.
The remaining patients underwent the less radical procedure, pleurectomy decortication or P/D. This surgery is still invasive, but spares the affected lung. Instead, P/D surgery relies on removal of the thickened areas of the pleural membrane, any visible tumors in the chest cavity, and sometimes may entail removal of the lining of the heart or other impacted organs or tissues.
Following their surgeries, all of the patients were treated with a heated intraoperative chemotherapy of combination gemcitabine and cisplatin. Cisplatin has often been used in the treatment of pleural mesothelioma with pemetrexed (Alimta®) as a first-line therapy, and has also been tested as a heated chemotherapy solution. Gemcitabine is a newer chemotherapy drug that has been approved to treat several cancers, including non-small cell lung cancer. Clinical trials have tested the drug with cisplatin and carboplatin applied intravenously, which has shown mixed effects on survival rate.
The study utilized a 3-plus-3 design, increasing the dosage of gemcitabine by 100 mg intervals. Through this process, the researchers ultimately established a maximum tolerable level of gemcitabine of 1000 mg/m2. Although past studies of systemic gemcitabine plus cisplatin showed little success, the researchers found an average survival of 20.3 months, with 10.7 months progression-free. This is a marked improvement on the average prognosis of pleural mesothelioma, which is typically just 6 to 12 months.
Overall, the researchers noted the combination therapy applied as a heated chemotherapy solution following surgery is both safe and effective. With further study, researchers hope to continue to improve the combination treatment and further extend survival.