A retrospective chart review of 216 pediatric patients treated with cisplatin at St. Louis Children’s Hospital from August1,1990 to March 31, 2015 was conducted. Data were gathered on cisplatin-cumulative dose, number of doses, amount per dose, doses per cycle, dosage time, and dosage reduction as well as age, gender, diagnosis, concomitant use of carboplatin, radiation exposure to the head or other parts of the body, most recent audiogram results, presence of hearing loss prior to and following cisplatin therapy, and right/ left ear toxicity grades according to International Society of Pediatric Oncology grade.

Patients had to have a normal baseline audiogram with a subsequent ear-specific behavioral audiogram testing out to 6,000 and/or 8,000 Hz. Baseline testing included sound field and normal auditory brainstem response (ABR). (Sound field testing refers the method of audiology testing that takes place in a sound-isolated room via speakers.) ABR is an electroencephalographic test of auditory brainstem function that is based on responses to auditory stimuli. Patients had to have normal hearing in at least one ear at baseline. Data were gathered on the “most recent audiogram,” which had to be a behavioral hearing test, which is an age-appropriate audiometric test based on a child’s behavioral response to sound.

Of the 216 patients, 71% (153 patients) had sufficient audiometric data to assess hearing status. The majority of patients (56%) were male with a mean age of 8.3 years (range: 0.2-19.9 years). Within this group, 73% experienced hearing loss. The average time since the last cisplatin administration to the last recorded (i.e, “most recent”) audiogram was 3.73 years. One-fifth of patients also received carboplatin in addition to cisplatin, and 60% received radiation exposure to any body part, with 43% receiving radiation to the head. The mean cisplatin cumulative dose was 391.2 mg/m2 (range: 90-1,000 mg/m2) with an average dose of 74.1 mg/m2 (range: 20-150 mg/m2). Patients received cisplatin for an average of 2.1 doses per cycle during an average of 3.7 cycles. On average, patients received 6.9 doses with a range of 1 to 30 doses with an average prescribed dose time (infusion time) of 4.4 hours.

Younger age (odds ratio [OR] = 0.9, CI, 0.84-0.97), radiation to any part of the body (OR = 3.2, CI, 1.3-7.9), larger amount of cisplatin per dose [OR = 3.2; CI, 1.3-7.9), and a higher cumulative cisplatin dose (OR = 1.018, CI, 1.002-1.033) were significantly associated with an increased risk of hearing loss on multivariant analysis. Based on SIOP grades, only 28% had normal hearing, 37% had a SIOP grade of 1-2 (i.e., >20 decibel hearing loss at 4,000 hertz or greater) and 35% had a SIOP grade of 3 to 4 (i.e., >20 decibels at 2,000 or 3,000 Hertz and above or >40 decibels of hearing loss at 2,000 Hertz or above) with higher scores indicating worsening hearing loss. Worsening SIOP grades were associated with age, radiation to any part of the body and the amount of cisplatin per dose with cumulative cisplatin doses trending towards significance (P = .057).

The article provides useful information for pharmacists caring for oncologic pediatric patients related to the risk factors most associated with irreversible cisplatin-induced hearing loss.

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