Clinical activity of mTOR inhibition in combination with cyclophosphamide in the treatment of recurrent unresectable chondrosarcomas

Rinat Bernstein-Molho, Yehuda Kollender, Josephine Issakov, Jacob Bickels, Shlomo Dadia, Gideon Flusser, Isaac Meller, Ronit Sagi-Eisenberg, Ofer Merimsky

Research output: Contribution to journalArticlepeer-review

Abstract

Objective Chondrosarcomas (CS) represent a heterogeneous group of rare sarcomas, poorly responsive to chemotherapy or radiotherapy. When local therapies in recurrent or metastatic disease are exhausted, chemotherapy plays a marginal role. Different molecular pathways have been shown to be activated in CS. In this retrospective study, we summarize our experience in treating a cohort of patients with recurrent unresectable CS with a combination of sirolimus (SIR) and cyclophosphamide (CTX). Patients and methods Ten consecutive patients with unresectable CS were offered off-label treatment with SIR and CTX between 2007 and 2012. Tumor response, progression- free survival (PFS), adverse events, and other relevant clinical data were analyzed. Results The median patients' age was 49 (range 28-68). Median disease-free interval since the primary diagnosis was 22.5 months. Median time from the disease recurrence to initiation of SIR and CTX treatment was 21.7 months due to additional local surgical treatments, excision of metastases, or slow asymptomatic progression. One (10 %) objective response was observed, and six (60 %) patients had stabilization of disease for at least 6 months. Three patients had progressive disease. Median PFS was 13.4 months (range 3-30.3). No significant adverse events were observed. Conclusions Although advanced CS remains an incurable disease, our experience suggests that a combination of SIR and CTX is well tolerated and may have meaningful clinical activity with disease control rate of 70 %. Further prospective studies are warranted.

Original languageEnglish
Pages (from-to)855-860
Number of pages6
JournalCancer Chemotherapy and Pharmacology
Volume70
Issue number6
DOIs
StatePublished - Dec 2012

Keywords

  • Chondrosarcoma
  • Cyclophosphamide
  • Sirolimus
  • mTOR

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