Efficacy and safety of sirolimus in the treatment of complicated vascular anomalies

Denise M. Adams*, Cameron C. Trenor, Adrienne M. Hammill, Alexander A. Vinks, Manish N. Patel, Gulraiz Chaudry, Mary Sue Wentzel, Paula S. Mobberley, Lisa M. Campbell, Christine Brookbank, Anita Gupta, Carol Chute, Jennifer Eile, Jesse McKenna, Arnold C. Merrow, Lin Fei, Lindsey Hornung, Michael Seid, A. Roshni Dasgupta, Belinda H. DickieRavindhra G. Elluru, Anne W. Lucky, Brian Weiss, Richard G. Azizkhan

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

372 Scopus citations

Abstract

BACKGROUND AND OBJECTIVES: Complicated vascular anomalies have limited therapeutic options and cause significant morbidity and mortality. This Phase II trial enrolled patients with complicated vascular anomalies to determine the efficacy and safety of treatment with sirolimus for 12 courses; each course was defined as 28 days. METHODS: Treatment consisted of a continuous dosing schedule of oral sirolimus starting at 0.8 mg/m2 per dose twice daily, with pharmacokinetic-guided target serum trough levels of 10 to 15 ng/mL. The primary outcomes were responsiveness to sirolimus by the end of course 6 (evaluated according to functional impairment score, quality of life, and radiologic assessment) and the incidence of toxicities and/or infection-related deaths. RESULTS: Sixty-one patients were enrolled; 57 patients were evaluable for efficacy at the end of course 6, and 53 were evaluable at the end of course 12. No patient had a complete response at the end of course 6 or 12 as anticipated. At the end of course 6, a total of 47 patients had a partial response, 3 patients had stable disease, and 7 patients had progressive disease. Two patients were taken off of study medicine secondary to persistent adverse effects. Grade 3 and higher toxicities attributable to sirolimus included blood/ bone marrow toxicity in 27% of patients, gastrointestinal toxicity in 3%, and metabolic/ laboratory toxicity in 3%. No toxicity-related deaths occurred. CONCLUSIONS: Sirolimus was efficacious and well tolerated in these study patients with complicated vascular anomalies. Clinical activity was reported in the majority of the disorders.

Original languageEnglish (US)
Article numbere20153257
JournalPediatrics
Volume137
Issue number2
DOIs
StatePublished - Feb 2016
Externally publishedYes

ASJC Scopus subject areas

  • Pediatrics, Perinatology, and Child Health

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