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Combination treatment associated with tumor regression in sarcoma patients
A combination of two targeted therapies showed evidence of tumor regression in patients with treatment-resistant Ewing’s sarcoma or desmoplastic small round cell tumors, according to recent study results.
Researchers enrolled 20 patients in a phase 1 trial to evaluate the combination of cixutumumab, a human immunoglobulin G1 monoclonal antibody that targets insulin-like growth factor I receptor (IGF-IR), and the mTOR inhibitor temsirolimus (Torisel, Wyeth Pharmaceuticals).
Seventeen of the patients had Ewing’s sarcoma and three had desmoplastic small round cell tumors (DSRCT). The patients had undergone a median of six prior therapies.
“Effective treatment for relapsed sarcoma has remained largely elusive despite the fact that sarcomas are among the most common cancers of childhood and early adolescence,” Aung Naing, MD, assistant professor in the department of investigational cancer therapeutics at The University of Texas MD Anderson Cancer Center, and colleagues wrote in the study.
The patients with Ewing’s sarcoma received cixutumumab 6 mg/kg IV weekly and temsirolimus 25 mg IV weekly. The patients with DSRCT received cixutumumab 6 mg/kg IV weekly and temsirolimus 37.5 mg IV weekly. Treatment cycles lasted 4 weeks, and median follow-up was 8.9 months.
Seven of the 20 patients — five with Ewing’s sarcoma and two with DSRCT — responded to the combination.
The five patients with Ewing’s sarcoma who responded to the combination had tumor reductions of more than 20%. Two achieved complete response, including one for 27 months.
The two patients with DSRCT who responded to the combination had stable disease lasting more than 5 months.
Treatment results have been mixed when the two drugs have been evaluated as single agents, the researchers said. They hypothesized that the drug combination could fight off drug resistance.
One of six patients with Ewing’s sarcoma who previously developed resistance to a different IGF-IR inhibitor antibody achieved a complete response to the combination treatment.
The most common treatment-related adverse effects were reduced platelet levels (85%), mucositis (80%), elevated cholesterol (75%), high triglycerides (70%) and elevated blood sugar (65%). One patient developed diabetes, which eventually was managed with insulin and metformin.
Most toxicities were grade 1 or grade 2. The four best responders had grade-3 mucositis or grade-3 myelosuppression, such as thrombocytopenia or neutropenia, but those toxicities were controlled while maintaining drug dose, the researchers said.
“If we can manage the toxicity, patients should not be taken off treatment,” Naing said in a press release. “This is a really important message.”
Further studies with larger numbers of patients with Ewing’s sarcoma and DSRCT, as well as additional investigation into underlying resistance mechanisms in individual patients, are needed, the researchers said.
Disclosure: The research was supported by grants from the NCI.