RESUMO
INTRODUCTION: Data about the feasibility or stability of drugs prepared for intrathecal administration are scarce, especially concerning the possibility of mixing two or more compounds in the same syringe. We evaluated the stability of an extemporaneously prepared triple intrathecal therapy containing methotrexate, cytarabine, and methylprednisolone hemisuccinate. MATERIALS AND METHODS: Six mixtures containing 12.5 mg methotrexate, 50 mg cytarabine, and 40 mg methylprednisolone hemisuccinate, diluted to a final volume of 5â ml with water for injection, were prepared in polypropylene syringes on six different days. Syringes were stored protected from light either at room temperature (20°C) (n = 3) or refrigerated temperature (4°C) (n = 3). Samples were analyzed immediately after preparation and again at 0.5, 2, 4, 6, 8, and 24 h. The analysis was conducted with a high-performance liquid chromatography instrument equipped with a quaternary pump and diode array detector. pH was also assessed before every sample analysis. RESULTS: When mixed in a polypropylene syringe, the three drugs were stable at both temperatures tested. No degradation >10% was observed in any sample and pH remained between 7.0 and 7.5 over time. No precipitation or color change occurred. Among the three compounds, methylprednisolone hemisuccinate was the most labile as a slight temperature- and time-dependent degradation was observed. CONCLUSION: Triple intrathecal solution of methotrexate, cytarabine, and methylprednisolone hemisuccinate is stable for up to 24 h when stored in polypropylene syringes protected from light at 4°C and 20°C.
RESUMO
Biliary tract cancer is an uncommon cancer in developed countries. In localized stages, surgery is the cornerstone of treatment with curative purpose. Conversely in advanced stages, chemotherapy with platinum-gemcitabine combination is the standard of care. Biliary tract cancers are a biologically heterogeneous group of malignancies, which perhaps explains the failure of targeted therapies in unselected patient populations to demonstrate benefit in advanced disease, although there are promises in selected populations (e.g. PD1/PD-L1 positive, BRAFV600E-mutated or IDH1-mutant). In view of the limited benefit of second line therapies in metastatic biliary tract cancer, various targeted agents have been tested in progressive disease. Furthermore, several ongoing trials are using next-generation sequencing of multiple genes to identify molecular abnormalities in the tumors of patients with refractory cancers that may potentially be used in pretreated disease (e.g. FGFR or IDH genes). Immunotherapy with immune checkpoint inhibitors may be interesting for patients whose tumors have programmed cell death 1 ligand 1 (PD-L1) overexpression. Ongoing and future trials will further advance our knowledge toward the optimal treatment strategy for the management of biliary tract cancer in its different stages, starting from metastatic and then reaching early stages of disease. We here provided an overview of these novel treatment strategies for advanced biliary tract cancers not amenable of curative treatment modalities.