Efficacy of Initial Sirolimus Therapy for 27 Patients with Intractable Lymphatic Malformations

Abstract

Objective/Hypothesis: To evaluate the efficacy of initial sirolimus therapy in the treatment of intractable head and neck lymphatic malformations (LMs) in children.Study Design: Prospective open-label study.Methods: In this study, Twenty-seven children diagnosed with LMs were given oral sirolimus as primary treatment over a minimum 6-month trial. The major parameter to evaluate therapeutic outcome was percentage of lesion volume change compared with baseline. Average serum sirolimus concentrations, and adverse side effects, were monitored throughout the study period.Results: Fifteen girls and twelve boys, average age 27 months (16 days-171 months), constitute the study group. Treatment was deemed effective for twenty-three participants, judged as fair in seven, good in nine, and excellent in seven. Two patients had minimal improvement, and two had increased volume to some degree. Effectiveness differed among LMs subtypes with responsiveness of macrocystic LMs exceeding that of microcystic LMs (P < .05). Adverse drug reactions totaled 27 events in ten patients, the majority being mild with upper respiratory infections being most common.Conclusions: Sirolimus as initial therapy is effective in decreasing lesion volume in intractable LMs in head and neck region, especially in macrocystic subtypes. Although most cases cannot be completely cured, side effects are few and tolerable.

Efficacy of sirolimus in children with lymphatic malformations of the head and neck

“…In all, 28 case series and case reports and two prospective trials [ 31 , 36 ] including 105 children treated with sirolimus for LM of the head and neck, were included in this review (Table 1 ) [ 12 – 39 ]. Due to the inclusion criteria, the age of the patients ranged from newborn to 17 years.…”

“…In most studies, sirolimus was administered orally at an initial dosage of 0.8 mg/m 2 per dose, twice daily at 12-h intervals [ 13 , 17 , 19 , 21 , 23 – 26 , 28 , 34 , 36 , 39 ]. In other studies, this was modified to 0.8 mg/m 2 per day [ 29 ], 0.8 mg per day in three doses [ 32 ], or 0.08 mg/kg per day [ 30 ].…”

“…The target blood level was 10–15 ng/mL in seven studies [ 14 , 17 , 20 , 23 , 24 , 26 , 39 ], 5–15 ng/mL in four studies [ 16 , 28 , 31 , 34 ] and 4–12 ng/mL in two studies [ 25 , 30 ]. In one study each, 3.5–6 ng/mL [ 30 ], 4–8 ng/mL [ 21 ], 4–10 ng/mL [ 38 ], 4–13 ng/mL [ 36 ], 5–12 ng/mL [ 33 ], 10–12 ng/mL [ 27 ], 10–13 ng/mL [ 19 ] and 12–20 ng/mL [ 35 ] were the target concentrations. Eight studies did not report the target blood level of sirolimus [ 12 , 13 , 15 , 18 , 22 , 29 , 32 , 37 ].…”

“…In five studies no patients experienced side effects [ 15 , 22 , 29 , 30 , 37 ]. In the other 18 studies, different adverse effects were reported [ 16 , 17 , 19 – 21 , 23 – 28 , 31 , 33 – 36 , 38 , 39 ], the most common were hyperlipidemia, neutropenia and infections such as cellulitis. There was no reporting of adverse events graded according to Common Terminology Criteria for Adverse Events (CTCAE).…”

Evaluation of Anti Carcinogenic Activity of Trifolium pratense on Oral Cancer Cell- An in vitro Study

“…Also the use of these drugs may also lead to systemic toxicity which may sometimes become unnoticed and make the patients life under risk [6,7]. Hence the use of plant extract is essential as they have less toxicity or non toxic and less side effects when compared to chemically synthesised drugs [8].…”