different doses of sirolimus for the maintenance treatment of kaposiform hemangioendothelioma

Conditions: Hemangioendothelioma

Summary: the purpose of this study is to compare the efficacy and safety of different doses of sirolimus in the maintenance treatment of kaposiform hemangioendothelioma.

kaposiform hemangioendothelioma (khe) is a rare aggressive vascular neoplasm that occurs predominantly in infancy or early childhood, with an incidence of approximately 0.071/100,000. currently, sirolimus is a promising treatment modality for khe. most scholars consider sirolimus blood concentration of 5-15 ng/ml to be an effective therapeutic concentration, while 10-15 ng/ml is the most commonly used blood concentration. however, long-term higher dose sirolimus treatment can cause some common adverse effects, such as oral mucositis which affects the quality of life of the patient. finer control of the plasma concentration of sirolimus may contribute to the efficacy of treatment and reduce the incidence of complications. previous studies have found good efficacy of low-dose sirolimus maintenance treatment for khe. however, there is no high-level evidence to support this treatment strategy. therefore, we conducted this study to find out whether an early reduction in sirolimus dose would benefit the prognosis of the patients.

Eligibility criteria:
inclusion criteria: presenting a khe with the following characteristics: 1. male and female; 2. between 0 and 14 years of age; 3. diagnosis of khe as determined by: * biopsy; * compatible mri findings; * history and clinical features. 4. patients were required to have adequate liver, renal and bone marrow function, and absence of active infection 5. consent of parents (or the person with parental authority in families): signed and dated written informed consent. exclusion criteria: 1. patients contraindicated for the administration of sirolimus (e.g., those with an allergy to sirolimus or other rapamycin analog) 2. exposure to chemotherapy, embolization, corticosteroids, propranolol, sclerotherapy or any other investigational agents within 1 weeks before enrolment on study; 3. patients had a history of a major surgery within 2 weeks before enrollment; 4. patients who have a history of treatment with sirolimus or other mtor inhibitor; 5. any known evidence of significant local or systemic uncontrolled infection, defined as receiving intravenous antibiotics at the time of enrollment; 6. concurrent severe and/or uncontrolled medical diseases that could compromise participation in the study (e.g. uncontrolled diabetes, uncontrolled hypertension, severe malnutrition, chronic liver or renal disease, active upper gastrointestinal tract ulceration). 7. impairment of gastrointestinal function or chronic gastrointestinal disease that may significantly alter the absorption of sirolimus. 8. patients with inadequate liver function: total bilirubin higher than or equal to 1.5 × the upper limit of the normal (uln) for age and alanine aminotransferase and aspartate aminotransferase higher than or equal to 2.5 × the uln for age. 9. patients with inadequate renal function: 0-5 years of age maximum serum creatinine (mg/dl) of 0.8; 6-10 years of age maximum serum creatinine (mg/dl) of 1.0; 11-14 years of age maximum serum creatinine (mg/dl) of 1.2; 10. adequate bone marrow function: absolute neutrophil count lower than 1 × 109/l; 11. history of a malignancy within 5 years; 12. hiv infection or known immunodeficiency; 13. indication for treatment with corticosteroids, vincristine, interferon-α, sirolimus, or tacrolimus for an indication other than ih; 14. patients with an inability to participate in or follow-up during the study treatment and assessment plan; 15. inability to give informed consent.

Keywords: kaposiform hemangioendothelioma hemangioendothelioma sirolimus