An open-label study to evaluate sildenafil for the treatment of lymphatic malformations

Abstract

Background Lymphatic malformations (LM) can be challenging to treat. Mainstay interventions including surgery and sclerotherapy are invasive and can result in local recurrence and complications. Objective To assess the effect of 20 weeks of oral sildenafil on reducing LM volume and symptoms in children. Methods Seven children (4 boys, 3 girls; ages 13–85 months) with LMs were given oral sildenafil for 20 weeks in this open-label study. The volume of the LM was calculated blindly using magnetic resonance imaging performed before and after 20 weeks of sildenafil. LMs were assessed clinically on weeks 4, 12, 20, and 32. Both the physician and parents evaluated the LM in comparison to baseline. Results Four subjects had a LM volume decrease (1.0–31.7%). In 2 subjects, despite a LM volume increase (1.1–3.7%), clinical improvement was noted while on sildenafil. One subject had a 29.6% increase in LM volume and no therapeutic response. LMs of all 6 subjects who experienced a therapeutic response on sildenafil softened and became easily compressible. Adverse events were minimal. Limitations A randomized-controlled trial will be necessary to verify the effects of sildenafil on LMs. Conclusions Sildenafil can reduce LM volume and symptoms in some children.

Congenital chylothorax treated with oral sildenafil: a case report and review of the literature

“…Sildenafil is an established treatment for pulmonary hypertension in newborns and infants 5 and has recently shown promise as a treatment for lymphatic malformations. 3 Our patient had bilateral CC suspected to be due to congenital pulmonary lymphangiectasia.…”

“…Of these, sildenafil has been further evaluated in an open label trial for the treatment of children with lymphatic malformations. 3 The trial was conducted after a serendipitous observation in a child with an intrathoracic lymphatic malformation and idiopathic pulmonary hypertension. 4 The pulmonary hypertension was treated with sildenafil and during the course of treatment the lymphatic malformation reduced in size, then enlarged with discontinuation of sildenafil.…”

“…The parents declined an open lung biopsy and on day of life 23 the infant was started on oral sildenafil with the plan to continue treatment for 20 weeks as recently described for the treatment of lymphatic malformation. 3 Octreotide was weaned off over a 2-week period. The chylothorax resolved within 15 days of initiating sildenafil treatment, all chest tubes were removed by 18 days, and the infant was weaned from nasal continuous positive airway pressure to room air by 19 days.…”

“…2 Recently, oral sildenafil, a specific inhibitor of phosphodiesterase-5, was reported to be effective in resolving non-pulmonary lymphatic malformations in infants and young children. 3,4 We report a case of CC in a late preterm infant with congenital pulmonary lymphangiectasia where octreotide was not effective, but management with oral sildenafil was successful.…”

Primary Intestinal Lymphangiectasia and its Association With Generalized Lymphatic Anomaly

“…Cases have been described in which treatments such as sildenafil (31), propranolol (32)(33)(34), and bevacizumab have been effective (35), but cases of resistance to these drugs have also been reported (36,37). Sirolimus, an mTOR inhibitor, has been reported to improve pleural effusions and mediastinal mass size (38)(39)(40).…”