Ototoxicity from high‐dose use of platinum compounds in patients with neuroblastoma

Abstract

BACKGROUND. The young age of neuroblastoma patients makes them especially prone to the ototoxic effects of widely used treatments that feature aggressive use of platinum compounds. We present data defining the extent of the problem in a large series of neuroblastoma patients whose induction included high-dose cisplatin/etoposide (HD-P/E) as used in both the Memorial Sloan-Kettering Cancer Center N7 regimen and the Children's Oncology Group A3973 study.METHODS. N7/A3973 patients were divided into 3 groups: Group 1 had hearing tested after induction, that included 2 cycles of HD-P/E (cumulative cisplatin ¼ 400 mg/m 2 ); Group 2 had hearing tested after induction, that included 3 cycles of HD-P/E (cumulative cisplatin ¼ 600 mg/m 2 ); and Group 3 had hearing tested following carboplatin-containing myeloablative therapy administered after induction, that included 2 cycles of HD-P/E. Ototoxicity was scored by the Brock method.RESULTS. All 3 groups had similar clinical characteristics, including median age at diagnosis of about 3 years. Little or no hearing loss in the speech range (Grade 0/1) was documented in 21 (32%) of the 65 Group 1 patients, 5 (10%) of the 50 Group 2 patients, and 9 (15.5%) of the 58 Group 3 patients. Severe (Grade 3/4) deficits affected 25% of Group 1, 54% of Group 2, and 50% of Group 3 patients.Patients < 5 years at diagnosis had greater ototoxicity than older patients had, with adolescents/adults being the least affected. Findings were stable in repeated assessments over 2 or more years. CONCLUSIONS.Ototoxicity is a serious and pervasive problem in this patient population. Strategies to ameliorate ototoxicity without compromising on antitumor activity of treatments are urgently needed.

Neuroblastoma, childhood cancer survivorship, and reducing the consequences of cure

“…[5][6][7] Such survivorship research in the pediatric setting has focused primarily on the more common malignancies, such as acute lymphoblastic leukemia and Hodgkin's lymphoma, with very little systematic study on late effects of neuroblastoma, perhaps with the exception of documenting the permanent ototoxic effects of cisplatin and carboplatin. [8][9][10][11][12] From the present study 4 and similar clinical followup work by Laverdie`re et al 13 and others, 14 we can reach a brief understanding of the risks for multi-organ sequelae among survivors of advanced stage neuroblastoma. The most prominent are endocrine impairments, including short stature, hypothyroidism and ovarian and testicular dysfunction; musculoskeletal complications, including kyphosis and scoliosis, significant dental abnormalities, slipped capital femoral epiphysis, fractures, fibrosis and hypoplasia; major organ system impairment, most notably serious renal dysfunction, but also cardiac toxicity and lung fibrosis or other pulmonary problems; neurological disorders, including opsoclonus myoclonus (opsoclonus ataxia), neurogenic bladder, and paresis and paraplegia; and sensory impairments, including chronic pain, parasthesia, cataracts and neurosensory hearing loss.…”

Prospective evaluation of cisplatin- and carboplatin-mediated ototoxicity in paediatric and adult soft tissue and osteosarcoma patients

“…Previous studies have revealed hearing impairments mainly in patients <5 years old (20,24,25). In the adult group, hearing impairments were identified in 6/17 (35.3%) patients.…”

Report on hearing loss in oncology

“…Audiologically, there are monitoring proposals using conventional frequencies (Testa et al 15 , Kushner et al 16 , Marshall et al 17 , Toral-Martinnon et al 18 ), monitoring proposals using transient otoacoustic emissions (Liberman 19 ) or distortion products (Biro et al 20 ; Hyppolito et al 21 ), and monitoring proposals using high frequencies (over 8000 Hz) (Garcia 22 ), which may be first affects by ototoxic drugs. In this case, patients with hearing loss normally do not complain and not always perceive loss of hearing (Liberman 23 ).…”