APHON Pediatric Chemotherapy-Biotherapy Renewal

be reversible when the cytarabine or agent contributing to the syndrome is discontinued; however, in some cases symptoms have persisted after discontinuation of the offending drug. Methotrexate. Methotrexate is a mainstay antineoplastic for hematologic malignancies and solid tumors alike. It can be administered through a variety of routes: oral, subcutaneous, intramuscular, intravenous, and intrathecal (IT). Methotrexate neurotoxicity, however, is typically associated with doses that are administered intrathecally or high intravenous doses (Peddi et al., 2014). There are several neurotoxicities associated with intrathecal administration of methotrexate including aseptic meningitis and transverse myelopathy. Aseptic meningitis should be considered in the differential for a patient exhibiting symptoms such as headache, stiff neck, mild fever, nausea and vomiting several hours after an intrathecal dose of methotrexate (Verstappen et al., 2003). Symptoms of aseptic meningitis due to IT methotrexate administration can last anywhere between 12 and 72 hours (Verstappen et al., 2003). Transverse myelopathy may occur after several IT methotrexate injections and can include symptoms of back pain that may radiate to the legs, sensory loss, bowl and bladder dysfunction and paraplegia. Thankfully, this toxicity is not long lasting and will resolve on its own (Peddi et al., 2014). Delayed methotrexate neurotoxicity or encephalopathy can also be found in patients who have received high intravenous doses of methotrexate or those who have received IT doses of methotrexate. This delayed leukoencephalopathy may occur six months or more after methotrexate administration and can be chronic. Symptoms of delayed methotrexate neurotoxicity include: progressive dementia, gait disturbances, hemiparesis, aphasia seizure and death. Radiation therapy administered concurrently with methotrexate has been associated with increased risk for developing delayed leukoencephalopathy (Peddi et al., 2014). A rare but potential complication of intrathecal methotrexate therapy may also include changes in the white matter that can manifest as a transient or persistent neurologic dysfunction. This neurologic dysfunction can first appear as facial nerve weakness, speech disturbance, seizures, hemiparesis, or an obtunded level of consciousness. It usually occurs within 2 weeks of a patient’s receiving intrathecal therapy (Bhojwani et al., 2014). The nurse caring for a patient exhibiting these signs and symptoms after receiving intrathecal methotrexate should advocate for further work-up and imaging to rule out white matter changes (Ramli et al., 2020; Yim et al., 1990). 5-fluorouracil. 5-fluorouracil (5-FU) is a cell-cycle-specific antimetabolite that is given to treat germ cell tumors and hepatoblastoma in the pediatric oncology setting, but it can also be used to treat gastrointestinal, head and neck, and breast cancers. Administration can be intravenous or by mouth. Patients with a deficiency of the dihydropyrimidine dehydrogenase enzyme are at greater risk for 5-FU-related toxicities, including neurotoxicities, because this enzyme is responsible for the metabolic clearance of 5-FU from the body. This drug does cross the blood- brain barrier, and high concentrations of 5-FU can be found in the cerebellum. As a result, cerebellar toxicity can be seen with this drug. Symptoms of cerebellar toxicity include ataxia, dysarthria, dysmetria, extraocular muscle abnormalities, optic nerve neuropathy, and extrapyramidal symptoms. Leukoencephalopathy, although rare, has also been reported with 5- FU administration (Peddi et al., 2014).