SUPPORTIVE CARE OF CHILDREN WITH CANCER: RECOGNITION AND MANAGEMENT OF CHEMOTHERAPY-INDUCED NEUROTOXICITY BACKGROUNDA.
Signs and symptoms may be difficult to recognize because they are woven into a background of underlying disease, metabolic abnormalities, psychologic responses, and the effects of other medications.B. Neurologic toxicity may occur with the first course of treat-ment or with subsequent courses.C. Neurotoxicity generally occurs with high-dose therapy andwhen the cumulative dose is high.D. Neurotoxicity may be seen months or years after the com-pletion of chemotherapy.
MONITORING FOR NEUROTOXICITYA. HistoryQuestion the patient and family about numbness, tingling, vertigo, or visual disturbances.Question the patient’s family about changes in personality, affect, or lethargy.Inquire about school and job performance and social and psychological well-being during long-term follow-up visits.B. Physical examinationPhysical examination with serial neurologic examinations is the most useful tool for detecting toxicity.Decreases in deep tendon reflexes, especially in the Achilles tendon, are among the earliest signs of chemotherapy-induced peripheral neuropathy.Loss of proprioception and vibratory sensation also indicate peripheral neuropathy.Changes in gait may indicate neurotoxicity. Observe toe walk, heel walk, and tandem walk. Changes in the ability to perform these tasks may indicate peripheral neuropathy or acute cerebellar syndrome.C. AudiometryObtain audiometric evaluation before beginning cisplatin and before every other course of therapy.D. Monitor cumulative dose calculation for cisplatin and vincristine.
MODIFICATION OF THERAPYA. Treatment ModificationsThe following treatment modifications are only suggestions. Modification of treatment should be based on the child’s diagnosis, stage of therapy, available alternatives, and the judgment of the clinician.B. VincristineDoses >10—15 mg/m2 may lead to neuropathy.Grades 1 and 2 toxicity require no modification.For grades 3 and 4 toxicity, hold the drug until symptoms subside or stabilize. Subsequent doses should be either decreased or omitted.Trigeminal nerve toxicity results in jaw pain.a. Treat with acetaminophen.b. This symptom does not usually recur.c. Do not modify the dose.5. Anticipate autonomic neuropathy resulting in constipation.a. Treat with laxatives such as lactulose, Pericolace, orSenokot S.b. Prevent with Senokot S or increase dietary fiber.6. Treat symptoms of syndrome of inappropriate antidiuret-ic hormone. It is usually not necessary to not modify thevincristine dose unless serum sodium <130 mEq/L.C. CisplatinDo not modify treatment for grade 1 or 2 toxicity.For grade 3 or 4 toxicity, hold the drug until the symptoms subside or stabilize. Either decrease or omit subsequent doses.High-frequency hearing loss occurs at cumulative doses of 270-450 mg/m2.Peripheral neuropathy occurs at cumulative doses of 300-600 mg/m2.May cause Lhermitte sign (sensation of tingling or electric shock in arms and legs when neck is flexed). Do not modify therapy.D. MethotrexateNo modifications are needed for grade 1 or 2 toxicity.For grade 3 or 4 toxicity, hold the drug until symptoms resolve or stabilize. Reduce or omit further doses.Patients receiving high-dose methotrexate may develop acute encephalopathy with the following symptoms.a. Seizuresb. Confusionc. Hemiparesisd. Dysarthria4. High-dose methotrexate may be associated with thedevelopment of leukoencephalopathy.a. Symptoms include:i. Personality changesii. Progressive dementiaiii. Focal seizuresiv. Changes in level of consciousnessb. Follow the patient with serial magnetic resonanceimaging scans.c. Omit further methotrexate treatment.5. Acute encephalopathy sometimes occurs after intrathe-cal therapy.a. Symptoms include:i. Feverii. Nausea and vomitingiii. Headacheiv. Lethargyv. Paresisb. The decision to stop or continue intrathecal therapymust be made on an individual basis.E. Ifosfamide1. Symptoms of toxicity include:a. Hallucinationsb. Confusionc. Cranial nerve dysfunctiond. Cerebellar syndromee. SeizuresNeurotoxicity is more common when serum albumin is low or infusions are rapid.No modifications are needed for grade 1 or 2 toxicityReduce or omit further doses for grade 3 or 4 toxicity.F. L-AsparaginaseL-Asparaginase may cause a mild transient encephalopathy. Also consider intracranial bleeding or clot.G. 5-Fluorouracil5-Fluorouracil may produce the cerebellar syndrome.Reduce or omit further doses.*40\168\2*
