Evaluation of ototoxicity in children with cancer who received cisplatin and/or carboplatin during treatment

Objective: To evaluate cisplatin, carboplatin induced ototoxicity in children with cancer. Method: Medical records of 784 children with the diagnosis of lymphoma and malignant solid tumor treated at our pediatric oncology center from 1988 to 2012 were evaluated retrospectively for receiving cisplatin and/or carboplatin. Characteristics of patients who recieved platinum, details of platinum treatment, co-administration of other ototoxic drugs, head/neck radiotherapy, follow up audiologic records were analyzed. Patients without audiological assessments were invited for follow up audiological assessments. The audiological tests included pure tone audiometry, transient oto-acoustic emissions, auditory brainstem response. Ototoxicity were graded according to Brock?s hearing loss criteria.Results: There were 221 (28%) patients who received cisplatin and/or carboplatin. Baseline audiological assessments were available in 39 (17.6%) patients. Follow up audiological assessments were available in 26% of patients (n:58), and this ratio increased to 45% (n:100) by invitation of patients for follow up audiologic examination. In our study, there were 97 eligible patients. The median age at treatment was 6.3 years (1mos-19yrs), M:F ratio was 0.99. There were 57 patients (59%) in group 1 (cisplatin-only), 21 patients (21.5%) in group 2 (cisplatin and carboplatin), and 19 patients (19.5%) in group 3 (carboplatin-only). In group 1 65%, and in group 2 48% of patients received cisplatin by divided doses schema; in groups 2 and 3 carboplatin had been administered by single dose schema. The median audiometry time after diagnosis was 20 months (1mo?16yrs). In follow-up, high frequency hearing loss was detected in 30% of patients. According to the Brock?s grading system 16 patients (55%) had grade 1, 8 patients (27.6%) had grade 2, 3 patients (10.3%) had grade 3, two patients (6.9%) had grade 4 ototoxicity. Brock?s grade 1-4 ototoxicity incidence was 33% (n:19) in group 1, 43% (n:9) in group 2, and %5 (n:1) in group 3. Mean diagnosis age was found significantly different between patients with (n:29) or without (n:68) ototoxicity (p:0.003). At diagnosis, 83% of patients having ototoxicity was ?5-year-old. Ototoxicity was nor different between boys and girls. Between group 1 and 2; between the cumulative dose of cisplatin <400mg/m2 and ?400mg/m2; and between patients who received cisplatin by single dose and divided doses schema, incidence of ototoxicity was not different. Mean cisplatin and carboplatin doses was not different between patients with or without ototoxicity. Ototoxicity was found significantly higher in patients who received cisplatin and head and neck radiotherapy (p:0.003), and also cisplatin and aminoglycosides (p:0.001). Bleomycin was not cause significant difference on ototoxicity. The median age at treatment for patients with ototoxicity was 11 years (0-19), and 20 of them (69%) received aminoglycosides, 12 of them (41%) received head or neck radiotherapy. Seventy-seven percent (10/13) of patients with Brock?s grade 2-4 ototoxicity were female and 60% of them were pubertal/postpubertal girls. Head-neck radiotherapy had been done in 62% of patients who had grade 2-4 ototoxicity and oncologic diagnosis was intracranial tumor (n:5), nasopharyngeal carcinoma (n:2), and Hodgkin lymphoma (n:1) which required radiotherapy.Conclusion: Ototoxicity is the potential side effect of cisplatin and carboplatin treatment. Children older than 5 year old and adolescents are also susceptible to platinum related ototoxicity. Severe ototoxicity may occur in pubertal/postpubertal girls. In cisplatin receiving patients performing head-neck radiotherapy and aminoglycosides are increase the risk for ototoxicity. Patients with intracranial tumors (medulloblastoma, intracranial germ cell tumor), nasopharyngeal carcinoma who received radiotherapy have tendency to develop platinum related ototoxicity. Primary site of germ cell tumors is important to predict the risk of ototoxicity. Audiological assesments should be valued in clinical practice. Early detection of ototoxicity is important for management of treatment and also for improving quality of life.Ototoxicity is potential side effect of platinum treatment and close audiologic follow-up is necessary with audiology unit.