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


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.
The Unit of Bone and Soft Tissue Oncology, Division of Oncology, Tel-Aviv Sourasky Medical Center, Affiliated with the Sackler School of Medicine, Tel-Aviv University, Israel.
Rinat
R
Bernstein-Molho
Yehuda
Y
Kollender
Josephine
J
Issakov
Jacob
J
Bickels
Shlomo
S
Dadia
Gideon
G
Flusser
Isaac
I
Meller
Ronit
R
Sagi-Eisenberg
Ofer
O
Merimsky
D000328:Adult; D000368:Aged; D000903:Antibiotics, Antineoplastic / Q000008:administration & dosage / Q000009:adverse effects; D018906:Antineoplastic Agents, Alkylating / Q000008:administration & dosage / Q000009:adverse effects; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage* / Q000009:adverse effects*; D001859:Bone Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology*; D002813:Chondrosarcoma / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology*; D003520:Cyclophosphamide / Q000008:administration & dosage / Q000009:adverse effects; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D012189:Retrospective Studies; D020123:Sirolimus / Q000008:administration & dosage* / Q000009:adverse effects; D058570:TOR Serine-Threonine Kinases / Q000037:antagonists & inhibitors*; D016896:Treatment Outcome
D000903:Antibiotics, Antineoplastic; D018906:Antineoplastic Agents, Alkylating; D003520:Cyclophosphamide; C546842:MTOR protein, human; D058570:TOR Serine-Threonine Kinases; D020123:Sirolimus