A combination of sorafenib, nelfinavir, and sirolimus in a patient with progressive metastatic synovial sarcoma after chemotherapy.

Abstract

e20531 Background: We report the case of a 34-year-old man with a poorly differentiated synovial sarcoma localized to the kidney. The tumor was positive for the SYT-SSX2 fusion transcript and negative for EWS-FL11 and EWS-ERG. He received 6 cycles of adriamycin and ifosfamide after nephrectomy. 1 year after completing chemotherapy, metastatic disease was found in the form of lung nodules. This was treated with metastatectomy. New lung nodules were noted 1 month after surgery. 2 cycles of gemcitabine and docetaxel were given, but his disease continued to progress, leading to another metastatectomy. 6 months later, metastatic disease was again noted in the lungs. Sorafenib was initiated, and nelfinavir was added 1 month later. 2 months after starting sorafenib, CT chest showed a decrease in the size of 1 lung nodule with otherwise stable disease. 6 months after starting sorafenib, he was found to have progressive disease by CT and sirolimus was added. Dose adjustments were made for hand-foot skin reaction and diarrhea. Therapy was interrupted for a febrile illness during which progressive disease was noted. His disease remained stable once triple therapy was restarted. Methods: The RAF/MEK/ERK and mTOR/AKT pathways are implicated in the proliferation of synovial sarcoma. Due to cross talk between these pathways in which one is up regulated when the other is blocked and the up regulation of Akt secondary to mTOR inhibition, we treated our patient with a combination of therapy that would minimize pathway activation by way of these feedback loops. Informed consent was obtained from the patient. Results: Disease stabilization was achieved with a novel combination of a multi-kinase inhibitor, an AKT inhibitor, and an mTOR inhibitor in this patient with metastatic synovial sarcoma. The patient is doing well with tolerable side effects 21 months after initiating moleculary targeted therapy and 34 months after metastatic disease was found. Conclusions: A combination of moleculary targeted therapy may be useful in the treatment of metastatic synovial sarcoma which has progressed after chemotherapy.