Two targeted therapies act against Ewing's sarcoma tumors

April 1, 2012, University of Texas M. D. Anderson Cancer Center

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

The study was published simultaneously in , 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 .

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 that cause and survival, abnormal 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.

"This trial provides preliminary data indicating that combining two targeted agents can result in tumor regression and even complete remission in heavily pretreated patients with metastatic Ewing's sarcoma, including those whose tumors had progressed on an IGFR inhibitor alone," said study senior author Razelle Kurzrock, M.D., professor and chair of the Department of Investigational Cancer Therapeutics. "By giving combinations of drugs in a scientifically rational way, we may be able to overcome resistance to single agents and provide benefit to patients with advanced Ewing's sarcoma."

Managing Treatment Toxicities

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).

Naing noted that it is not unusual to see these side effects, which were mostly grade I or grade II in severity. He added that one of the patients developed diabetes, which was eventually managed with insulin and the diabetes medication metformin.

Non-hematologic side effects of the treatment included mucositis, fatigue, rash or itching, elevated AST/ALT, elevated creatinine, diarrhea, anorexia/weight loss, and nausea and vomiting. The ability to manage these and other treatment side effects is critically important, Naing said.

"Our four best responders had grade III mucositis or grade III myelosuppression, such as thrombocytopenia or neutropenia. 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."

Supportive Care Aids Treatment

According to the researchers, the study results suggest patients should receive supportive care that will help them achieve and maintain dose levels high enough to sustain their response.

"If we can manage the toxicity, patients should not be taken off treatment," Naing said. "This is a really important message."

Co-authors 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, as well as additional investigation into underlying resistance mechanisms in individual patients.

Explore further: Targeting the Ewing sarcoma family of tumors

Related Stories

Targeting the Ewing sarcoma family of tumors

July 1, 2011
The Max Cure Foundation and the Samuel Waxman Cancer Research Foundation have partnered to establish a fund in pediatric cancer research. With that goal in mind, the two Foundations are proud to announce the award of $100,000 ...

Less toxic combination of erlotinib and bevacizumab is effective non-small cell lung cancer patients

June 1, 2011
The standard treatment for patients with advanced non-small cell lung cancer (NSCLC) is a combination of two old-fashioned cytotoxic chemotherapy drugs. The combination, however, comes with substantial toxicity. Now, Fox ...

The path to personalized cancer treatment

March 28, 2012
In the largest study of its kind, researchers have profiled genetic changes in cancer with drug sensitivity in order to develop a personalised approach to cancer treatments. The study is published in Nature on Thursday 29 ...

Recommended for you

Single blood test screens for eight cancer types

January 18, 2018
Johns Hopkins Kimmel Cancer Center researchers developed a single blood test that screens for eight common cancer types and helps identify the location of the cancer.

How cancer metastasis happens: Researchers reveal a key mechanism

January 18, 2018
Cancer metastasis, the migration of cells from a primary tumor to form distant tumors in the body, can be triggered by a chronic leakage of DNA within tumor cells, according to a team led by Weill Cornell Medicine and Memorial ...

Researchers find a way to 'starve' cancer

January 18, 2018
Researchers at Vanderbilt University Medical Center (VUMC) have demonstrated for the first time that it is possible to starve a tumor and stop its growth with a newly discovered small compound that blocks uptake of the vital ...

The pill lowers ovarian cancer risk, even for smokers

January 18, 2018
(HealthDay)—It's known that use of the birth control pill is tied to lower odds for ovarian cancer, but new research shows the benefit extends to smokers or women who are obese.

These foods may up your odds for colon cancer

January 18, 2018
(HealthDay)—Chowing down on red meat, white bread and sugar-laden drinks might increase your long-term risk of colon cancer, a new study suggests.

Modular gene enhancer promotes leukemia and regulates effectiveness of chemotherapy

January 18, 2018
Every day, billions of new blood cells are generated in the bone marrow. The gene Myc is known to play an important role in this process, and is also known to play a role in cancer. Scientists from the German Cancer Research ...

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.