PURPOSE: The aim of this study was to avoid radiotherapy and to induce an objective response in children with low-grade glioma (LGG) using a simple chemotherapy regimen based on cisplatin and etoposide. PATIENTS AND METHODS: Thirty-four children (median age, 45 months) with unresectable LGG were treated with 10 monthly cycles of cisplatin (30 mg/m²/d on days 1 to 3) and etoposide (150 mg/m²/d on days 1 to 3). Tumor originated in the visual pathway in 29 patients, in the temporal lobe in two, in the frontal lobe in two, and in the spine in one. Eight children were affected by neurofibromatosis type 1. Objective tumor response and toxicity were evaluated by magnetic resonance imaging and neurologic and functional tests at 3-month intervals. RESULTS: An objective response was obtained in 24 (70%) of 34 patients, whereas the others had stable disease. None of the children were electively irradiated. In 31 previously untreated children, overall survival was 100% and progression-free survival was 78% at 3 years, with a median follow-up of 44 months. Acute toxicity was unremarkable; 28% patients evaluated for acoustic neurotoxicity revealed a loss of perception of high frequencies. CONCLUSION: Cisplatin and etoposide combined treatment is one of the most active regimens for LGG in children and allows avoidance of radiotherapy in the vast majority of patients.

Vincristine-induced peripheral neurotoxicity (VIPN) is a very common side effect of vincristine chemotherapy among pediatric patients with cancer. Neuropathy may be sensory, motor and/or autonomic, with consequent reduction, delay or discontinuation of vincristine-chemotherapy, but also pain, disability, reduced quality of life of patients and an increase in medical costs. Vincristine acts out its antineoplastic function by altering the normal assembly and disassembly of microtubules, with their consequent mitosis block and death. Vincristine leads to VIPN through a complex mechanism of damage, which occurs not only on the microtubules, but also on the endothelium and the mitochondria of nerve cells. Furthermore, both patient-related risk factors (age, race, ethnicity and genetic polymorphisms) and treatment-related risk factors (dose, time of infusion and drug–drug interactions) are involved in the pathogenesis of VIPN. There is a lack of consensus about the prophylaxis and treatment of VIPN among pediatric oncologic patients, despite several molecules (such as gabapentin, pyridoxine and pyridostigmine, glutamic acid and glutamine) having been already investigated in clinical trials. This review describes the molecular mechanisms of VIPN and analyzes the risk factors and the principal drugs adopted for the prophylaxis and treatment of VIPN in pediatric patients with cancer.

Platinum compounds are widely used in the treatment of pediatric tumors such as neuroblastoma, germ-cell tumors, osteosarcoma, retinoblastoma, hepatoblastoma, brain tumors (low-grade gliomas and medulloblastoma/PNET), and relapsed and refractory lymphomas. The three major platinum compounds (cisplatin, carboplatin, and oxaliplatin) have a similar pharmacokinetics profile and mechanism of action, but the differences in their chemical structure are responsible for their different antitumor activity and toxicity. In this review, we have described the main characteristics of cisplatin, carboplatin, and oxaliplatin, focusing on their toxic effects and possible strategies to prevent them to improve the clinical outcomes in pediatric cancer patients. The underlying mechanism of each platinum-related toxicity is shown together with the clinical manifestations. Furthermore, possible preventive strategies are suggested to reduce the negative impact of platinum compounds on the quality of life of children with cancer. Cisplatin seems to be mostly ototoxic and nephrotoxic, carboplatin mainly produces myelosuppression, whereas oxaliplatin induces predominantly peripheral sensory neurotoxicity. In contrast, nausea and vomiting can be linked to all platinum compounds, although cisplatin exerts the strongest emetic effect. A correct knowledge of pharmacokinetics and toxicological profile of platinum compounds may aid physicians prevent their toxicity on auditory, nervous, renal, and bone marrow function, improving the quality of life of pediatric cancer patients.

Aminoglycosides are broad-spectrum antibiotics largely used in children, but they have potential toxic side effects, including ototoxicity. Ototoxicity from aminoglycosides is permanent and is a consequence of its action on the inner ear cells via multiple mechanisms. Both uncontrollable risk factors and controllable risk factors are involved in the pathogenesis of aminoglycoside-related ototoxicity and, because of the irreversibility of ototoxicity, an important undertaking for preventing ototoxicity includes antibiotic stewardship to limit the use of aminoglycosides. Aminoglycosides are fundamental in the treatment of numerous infectious conditions at neonatal and pediatric age. In childhood, normal auditory function ensures adequate neurocognitive and social development. Hearing damage from aminoglycosides can therefore strongly affect the normal growth of the child. This review describes the molecular mechanisms of aminoglycoside-related ototoxicity and analyzes the risk factors and the potential otoprotective strategies in pediatric patients.

BACKGROUND: Prevention of meningeal recurrence achieved by intrathecal methotrexate (MTX) and systemic chemotherapy is part of standard acute lymphoblastic leukemia (ALL) treatment. Cranial irradiation has been a routine part of past protocol treatment but is currently reserved only for select subsets of patients. Central nervous system (CNS) prophylaxis may cause brain abnormalities such as intracerebral calcifications, cerebral atrophy, and white matter alterations. In addition, long‐term neuropsychologic sequelae following CNS prophylaxis have been investigated marginally in children cured for ALL.METHODS: To explore possible correlations between neuroimaging findings and neuropsychologic outcome, we used detailed cognitive tests to evaluate 21 children with ALL who received cranial irradiation (range, 18–24 Gy) plus intrathecal MTX as CNS prophylaxis. All children were followed prospectively once a year by cerebral computed tomographic scan and magnetic resonance imaging. All patients had continuous complete disease remission for at least 4 years and cognitive tests were performed after neuroradiologic examinations.RESULTS: White matter abnormalities were associated with poor performance only in a task exploring visual motor integration in about 50% of patients. Intracerebral calcifications correlate with the number of intrathecal MTX doses and with low scores in total intellectual quotient, performance intellectual quotient, and significant impairment in attention and visual motor integration tests. Girls are more vulnerable to the effects of CNS prophylaxis, whereas age at treatment and radiotherapy dose are not relevant to neuropsychologic outcome.CONCLUSIONS: Our results indicate the need for careful follow‐up of children's cognitive abilities because global intellectual measures often fail to detect specific disorders that may cause learning difficulties. Moreover, as the clinical implications of neuroimaging findings are often limited, periodic extensive evaluation by specific neurocognitive tests of mental abilities is recommended to detect early signs of cognitive impairment. Cancer 2002;95:2562–70. © 2002 American Cancer Society.DOI 10.1002/cncr.10997