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6 May 2012

Results of a phase II study of sirolimus and cyclophosphamide in patients with advanced sarcoma

Schuetze SM et al. – Sirolimus and cyclophosphamide were tolerated by the majority of patients. About 20% of patients had stable sarcoma for at least 6months but objective tumour response was infrequent.


Methods

Patients received 4mg sirolimus daily and 200mg cyclophosphamide d1-7 and 15-21 every 28days.

 

The primary objective was to estimate the 24-week PFS rate with a target of 25%.

 

Patients were followed for World Health Organisation (WHO) criteria tumour response by imaging every 8weeks.

 

Serum levels of sirolimus, lipids and vascular endothelial growth factor were measured.

 

Tumour tissue was analysed for mTOR, S6 ribosomal protein and cytochrome P450 3A4/5 by quantitative immunofluorescence.


Results

Forty-nine eligible patients were enrolled from September 2008 to December 2009.

 

Patients received a median of four cycles of therapy.

 

Starting doses of drugs were tolerated in 79%.

 

One patient achieved partial tumour response, 10 were progression-free for 24weeks and two completed 12 cycles of treatment.

 

Median PFS and overall survival (OS) were 3.4 and 9.9months, respectively.

 

Serious adverse events attributed to therapy occurred in 11% and included infection, pneumonitis and thrombosis.

 

Hypertriglyceridaemia from treatment and lower tumour phosphorylated-mTOR are associated with longer survival.