The daily combination of sirolimus with cyclophosphamide every other week appeared safe and well tolerated by most patients with advanced sarcoma who had undergone standard chemotherapy, according to study results.
Scott M. Schuetze, MD, PhD, clinical associate professor in the department of internal medicine at the University of Michigan, and colleagues enrolled 49 patients with advanced, high-grade osteosarcoma in the phase 2 trial from September 2008 to December 2009. The median age of the patients was 57 years.
Patients received sirolimus (Rapamune, Wyeth Pharmaceuticals) 12 mg daily on day 1, followed by 4 mg daily, plus 200 mg cyclophosphamide daily for 7 days every other week in 28-day cycles. Patients underwent a median of four cycles (range, 1-12).
The primary endpoint was PFS at 24 weeks.
The median PFS of 3.4 months and median OS of 9.9 months exceed those demonstrated in other studies involving treatment with temsirolimus (Torisel, Wyeth Pharmaceuticals) and are similar to those demonstrated in studies involving treatment with ridaforolimus (Merck and Ariad Pharmaceuticals).
Ten of the patients experienced PFS of at least 24 weeks, one more than the pre-trial benchmark determined to consider the drug combination “promising,” the researchers wrote.
One patient achieved partial tumor response and two patients completed 12 cycles of treatment.
“The results were considered similar to other active regimens but failed to produce markedly superior results compared to [mammalian target of rapamycin] inhibitor therapy alone,” Schuetze and colleagues wrote. “Comparative effectiveness trials will be needed to evaluate the role of sirolimus should [mammalian target of rapamycin] inhibitors become an important component of sarcoma chemotherapy.”
The secondary aim of the trial was to estimate the rate of clinically significant adverse events related to the drug combination.
Seventy-nine percent of patients tolerated the starting doses, researchers said. Serious adverse events attributed to the combination occurred in 11% of patients. They included infection, pneumonitis and thrombosis.