Adding an mTOR inhibitor to chemotherapy may help improve outcomes in the treatment of sarcomas, according to a new study published in the journal Clinical Sarcoma Research.1 Previous studies had suggested the addition of an mTOR inhibitior to chemotherapeutic agents was beneficial in sarcoma—however, now researchers are proposing a mechanism by which mTOR inhibition enhances the efficacy of chemotherapy. The belief is that it does so through the sensitization of the chemoresistant cancer stem cell (CSC) population.1
Matteo Trucco, MD, division of pediatric oncology, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University, Baltimore, Maryland, and colleagues examined chemoresistance of sarcoma CSCs following treatment with mTOR inhibitor temsirolimus (20 mg/m2 weekly) with the chemotherapeutic agent liposomal doxorubicin (30 mg/m2 monthly). The phase 2 trial included 15 patients with relapsed/refractory sarcoma (ClinicalTrials.gov Identifier: NCT00949325).
The researchers found that the median progression-free survival (PFS) was 315 days (range, 27 days to 799 days). The overall response rate, which was defined as stable disease or better, was 53% at 60 days. In this cohort, 9 patients previously had been treated with doxorubicin. The study showed this combination therapy was well tolerated. Some patients had pretreatment and posttreatment tumor biopsies, and the researchers found a correlation between response and decreased aldehyde dehydrogenase (ALDH) expression, and a correlation between biopsy-proven inhibition of mTOR and response.
The authors noted that this small study had a heterogeneous patient population, yet it showed this combination approach produced better results than previously reported with either agent given alone. They wrote that further study assessing ALDH expression in tumor cells before and after therapy would be warranted.
- Trucco MM, Meyer CF, Thornton KA, et al. A phase II study of temsirolimus and liposomal doxorubicin for patients with recurrent and refractory bone and soft tissue sarcomas. Clin Sarcoma Res. 2018;8:21.