Teaming Up Two Drugs Helps Ewing's Sarcoma Patients
A combination of two targeted therapies reduces tumors in treatment-resistant Ewing's sarcoma, a bone cancer that mainly strikes children, adolescents and young adults.
Results of the phase I clinical trial of the paired drugs were announced today at a news briefing at the AACR Annual Meeting 2012 by Aung Naing, M.D., assistant professor in MD Anderson's Department of Investigational Cancer Therapeutics. He presents the study Monday during the meeting's session on late-breaking clinical trials.
"These patients had been heavily, heavily pre-treated and are quite resistant to most other treatments," Naing said. "So we are encouraged that 5 of 17 patients with Ewing's sarcoma, about 29 percent, responded to the treatment, with two achieving complete responses."
One complete response lasted 27 months. Two of three patients with desmoplastic small-round-cell tumors also responded.
Researchers used a combination of cixutumumab, a human IgG1 monoclonal antibody that targets insulin growth factor receptor 1 (IGF-1R), and temsirolimus, an agent that inhibits mTOR, the mammalian target of rapamycin.
When the two drugs had been used as single agents, treatment results were mixed. Naing and colleagues theorized that combining the drugs would help stave off onset of drug resistance, a common occurrence and major obstacle in cancer treatment.
Together, the drugs address molecular pathways that cause cell proliferation and survival, abnormal blood vessel growth and resistance to chemotherapy and radiotherapy, Naing notes.
Managing side effects
The most common treatment-related side effects were reduced platelet levels (85 percent), mucositis (80 percent), elevated cholesterol (75 percent), high triglycerides (70 percent), and elevated blood sugar (65 percent). Most were low-grade.
The ability to manage these and other treatment side effects is critically important, Naing said, because the four best responders had grade 3 level side effects.
"Typically, a patient who develops these types of grade III toxicities would be removed from the study," Naing said. "But we were able to continue with the treatment after we received approval from the sponsor and notification from our institutional review board. Our patients received the benefits of continued treatment because we were able to manage their toxicities."
The next step: Study collaborators Robert Benjamin,M.D., professor and chair of MD Anderson's Department of Sarcoma Medical Oncology, and Joseph Ludwig, M.D., assistant professor in the department, plan further studies in larger numbers of patients with Ewing's sarcoma and DSRCT. Additional investigation into underlying resistance mechanisms in individual patients also is planned.
MD Anderson news release
Clinical Cancer Research paper