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

European Journal of Cancer, 04/27/2012

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.

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