Two Targeted Therapies Act Against Ewing's Sarcoma Tumors

Researchers control drug side effects for treatment gains in phase I trial

Newswise CHICAGO - A pair of targeted therapies shrank tumors in some patients with treatment-resistant Ewing's sarcoma or desmoplastic small-round-cell tumors, according to research led by investigators from The University of Texas MD Anderson Cancer Center reported at the AACR Annual Meeting 2012.

Five of 17 Ewing's sarcoma patients responded to the combination, with two achieving complete responses, one for 27 weeks. The researchers noted that the ability to manage patients' treatment-related side effects is vital to maintaining the therapy and slowing disease progression.

The study was published simultaneously in Clinical Cancer Research, a journal of the American Association for Cancer Research.

Ewing's sarcoma primarily affects the bones and occurs most often in teenagers and young adults and relapse is common, said lead researcher Aung Naing, M.D., assistant professor in MD Anderson's Department of Investigational Cancer Therapeutics.

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, or "mammalian target of rapamycin". The two drugs address molecular pathways that cause cell proliferation and survival, abnormal blood vessel growth and resistance to chemotherapy and radiotherapy.

Encouraging Responses in Treatment-Resistant Patients Twenty patients were enrolled in the phase I clinical trial - 17 with Ewing's sarcoma and three with desmoplastic small-round cell tumors (DSRCT). The patients were treated with cixutumumab (6 mg/kg i.v. each week) and temsirolimus (25 to 37.5 mg i.v. each week) in 4-week cycles. Median follow-up was 8.9 months.

"Seven of the 20 patients responded and have had stable disease for more than five months," Naing said. "Five of these responders have Ewing's sarcoma and have had tumor reductions of more than 20 percent. Treatment responses have lasted 8 to 27 months."

Naing added that these patients had undergone a median of six previous treatments. "They 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."

The investigators noted that when the two drugs had been used as single agents, treatment results were mixed. They theorized that combining the drugs would help stave off onset of drug resistance, a common occurrence and major obstacle in cancer treatment.

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Two Targeted Therapies Act Against Ewing's Sarcoma Tumors