Retinoblastoma is a relatively uncommon childhood tumor. If untreated, RB grows to fill the eye and destroys the ocular globe's internal architecture. Metastatic spread usually begins after the first 6 months, and death occurs within a matter of years. When treated, overall survival rounds 97%, the alkylating drug melphalan being the most extensively used chemotherapeutic agent in localized treatment. In our hospital, pediatric oncologists asked the Pharmacy Department for assessment in order to implement a new chemotherapy protocol for the treatment of advanced intraocular elegible retinoblastoma cases using melphalan administered directly through the ophthalmic artery. In this paper, we describe the protocol implementation carried out by our collaborative interdisciplinary team as well as the clinical outcomes of five cases treated with ophthalmic intra-arterial melphalan therapy. Oncology pharmacists can contribute with their knowledge to the implementation process of new collaborative practice protocols recommending doses, predicting possible adverse effects and assessing about drug stability and elaboration, packaging and administration methods.
Background
Sinusoidal obstruction syndrome (SOS) is an important non-haematological toxicity in patients who have received chemotherapy for haematopoietic stem cell transplantation (HSCT). In March 2013, European Medicines Agency refused marketing authorisation for the orphan drug defibrotide to prevent and treat SOS. In July 2013, after re-examination, defibrotide had a new positive opinion for marketing authorisation but only for treatment.
Purpose
To investigate the effectiveness, safety and cost of defibrotide for SOS.
Materials and methods
Retrospective observational study (Period: January 2009–September 2013). We analysed patients with SOS treated with defibrotide. Response criteria were defined as total serum bilirubin <2 mg/dl and resolution of multiple organ failure (MOF), including renal (recovery of normal creatinine value and lack of dialysis dependence), pulmonary (no oxygen dependence) and central nervous system (absence of encephalopathy) function. Evolution of the Baltimore criteria, including hepatomegaly, ascites and weight gain was measured. Secondary endpoint was survival by 100 days post-HSCT. Adverse events related to defibrotide administration were also retrieved.
Results
Eleven patients (five adults (mean age: 55.7(SD = 4.3) years) and four children (3.1(SD = 1.3)) received defibrotide at a dose of 6.25 mg/kg every 6 h (two patients received 10 mg/kg/6 h). Median duration of treatment was 9 days (range: 5–25).
Overall complete response was achieved in seven patients (63.6%), all four children and only three adults. 45.5% of patients had completely recovered from hepatomegaly at the end of defibrotide administration. Six of the eight patients with ascites and one patient with encephalopathy recovered their normal status. All patients reduced their weight gain after defibrotide treatment. 100 day post-HSCT survival was 72.7%.
Three patients presented haemorrhagic episodes during defibrotide treatment (two gastrointestinal episodes and one nasal bleeding). Median cost per patient was 19,180 € (range 5,480–41,100 €).
Conclusions
According to our limited results, defibrotide is an effective option for SOS treatment in children, although cost per patient is high. Cost-effectiveness studies comparing treatment for SOS with and without defibrotide are needed.
No conflict of interest.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.