An important new study from one of the country’s top mesothelioma research labs has found a way to significantly boost the impact of chemotherapy on mesothelioma patients who are not eligible for surgery.
Dr. Raffit Hassan and his colleagues at the National Cancer Institute have been focusing their efforts on an immunotoxin – a potent toxin inked to an antibody – to selectively target mesothelioma cells. The immunotoxin, called SS1P, is designed to target a protein called mesothelin, which is overexpressed in mesothelioma cells.
While previous studies have shown some promise in SS1P treatment by itself, especially when the immune system is suppressed, the newest study tests the value of SS1P in combination with the most popular mesothelioma chemotherapy drugs, pemetrexed and cisplatin.
The new Phase I study included 24 patients with stage III or IV mesothelioma who had not yet been treated with chemotherapy. Patients received between 25 and 55 mcg/kg of SS1P along with their regular chemotherapy on days 1, 3 and 5 during their first and second chemotherapy cycles. Tumor response was evaluated every 6 weeks.
“Of 20 evaluable patients, 12 (60%) had a partial response, 3 had stable disease and 5 had progressive disease,” reported Dr. Hassan in a summary of the findings in Cancer. Even more encouraging is the fact that, among the 13 patients who received the maximum tolerated dose of SS1P, 77% experienced some reduction in the size of their mesothelioma tumors and 1 had stable disease. Side effects of SS1P treatment were few and included fatigue, reduction in the protein albumen, back pain, and low blood pressure.
Among the mesothelioma patients who responded to the combination treatment, the research team found a significant decrease in serum levels of mesothelin, as well as other cancer indicators. The study concludes, “SS1P given with pemetrexed and cisplatin is safe and well tolerated and exhibits significant antitumor activity in patients with unresectable, advanced pleural mesothelioma.”
Now that safe dosing levels have been established, the next step will be to test the effectiveness of SS1P in a larger group of mesothelioma patients. Mesothelioma is a rare but aggressive cancer that typically occurs in people with a history of exposure to asbestos. The disease is highly resistant to standard cancer treatments, including chemotherapy, and claims the lives of an estimated 2,500 people in the U.S. each year.
Hassan, R et al “Phase I study of the antimesothelin immunotoxin SS1P in combination with pemetrexed and cisplatin for front-line therapy of pleural mesothelioma and correlation of tumor response with serum mesothelin, megakaryocyte potentiating factor, and cancer antigen 125”, July 2, 2014, Cancer, Epub ahead of print