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A pair of targeted therapies shrank tumors in some patients withtreatment-resistant Ewing's sarcoma or desmoplastic small-round-cell tumors, according to research ledby investigators from The University of Texas MD Anderson CancerCenter 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. Theresearchers noted that the ability to manage patients'treatment-related side effects is vital to maintaining the therapyand 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 oftenin teenagers and young adults and relapse is common, said leadresearcher Aung Naing, M.D., assistant professor in MD Anderson'sDepartment of Investigational Cancer Therapeutics. Researchers used a combination of cixutumumab, a human IgG1monoclonal 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 molecularpathways that cause cell proliferation and survival, abnormal bloodvessel growth and resistance to chemotherapy and radiotherapy. Encouraging Responses in Treatment-Resistant Patients Twenty patients were enrolled in the phase I clinical trial - 17with Ewing's sarcoma and three with desmoplastic small-round celltumors (DSRCT). The patients were treated with cixutumumab (6 mg/kgi.v. each week) and temsirolimus (25 to 37.5 mg i.v. each week) in4-week cycles. Median follow-up was 8.9 months. "Seven of the 20 patients responded and have had stable disease formore than five months," Naing said. "Five of these responders haveEwing's sarcoma and have had tumor reductions of more than 20percent. Treatment responses have lasted 8 to 27 months." Naing added that these patients had undergone a median of sixprevious treatments. "They had been heavily, heavily pre-treatedand are quite resistant to most other treatments," Naing said. "Sowe are encouraged that 5 of 17 patients with Ewing's sarcoma-about29 percent-responded to the treatment, with two achieving completeresponses." The investigators noted that when the two drugs had been used assingle agents, treatment results were mixed. They theorized thatcombining 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 twotargeted agents can result in tumor regression and even completeremission in heavily pretreated patients with metastatic Ewing'ssarcoma, including those whose tumors had progressed on an IGFRinhibitor alone," said study senior author Razelle Kurzrock, M.D.,professor and chair of the Department of Investigational CancerTherapeutics. "By giving combinations of drugs in a scientificallyrational way, we may be able to overcome resistance to singleagents and provide benefit to patients with advanced Ewing'ssarcoma." Managing Treatment Toxicities The most common treatment-related side effects were reducedplatelet levels (85 percent), mucositis (80 percent), elevated cholesterol (75 percent), high triglycerides (70 percent), and elevated bloodsugar (65 percent). Naing noted that it is not unusual to see these side effects, whichwere mostly grade I or grade II in severity. He added that one ofthe patients developed diabetes , which was eventually managed with insulin and the diabetesmedication 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 tomanage these and other treatment side effects is criticallyimportant, Naing said. "Our four best responders had grade III mucositis or grade IIImyelosuppression, such as thrombocytopenia or neutropenia.Typically, a patient who develops these types of grade IIItoxicities would be removed from the study," Naing said. "But wewere able to continue with the treatment after we received approvalfrom the sponsor and notification from our institutional reviewboard. Our patients received the benefits of continued treatmentbecause we were able to manage their toxicities." Supportive Care Aids Treatment According to the researchers, the study results suggest patientsshould receive supportive care that will help them achieve andmaintain dose levels high enough to sustain their response. "If we can manage the toxicity, patients should not be taken offtreatment," Naing said. "This is a really important message." Co-authors Robert Benjamin, M.D., professor and chair of MDAnderson's Department of Sarcoma Medical Oncology, and JosephLudwig, M.D., assistant professor in the department, plan furtherstudies in larger numbers of patients with Ewing's sarcoma andDSRCT, as well as additional investigation into underlyingresistance mechanisms in individual patients. Additional References Citations. The e-commerce company in China offers quality products such as China Tattoo Aftercare Cream , Tattoo Foot Switch Manufacturer, and more. For more , please visit Tattoo Aftercare Cream today!
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