Younger Patients Treated with Systemic Carboplatin at Higher Risk of Ototoxicity


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Patients younger than 6 months at the start of systemic carboplatin treatment for retinoblastoma have a significant risk of developing hearing loss, according to a study in the Journal of Clinical Oncology. A review of audiologic test results of 60 patients with retinoblastoma who received front-line treatment with systemic carboplatin and vincristine found that 12 patients had hearing loss at some time after treatment, 10 with sustained hearing loss. Of those 10, 9 were less than 6 months of age when treatment began.

“Age at the start of chemotherapy was the only risk factor identified as a significant predictor of sustained hearing loss,” the investigators reported. “The 10-year cumulative incidence of hearing loss was 39.0% ± 10.6% for patients younger than 6 months of age vs only 8.3% ± 4.7% for patients 6 months of age and older at the start of treatment (P =.004),” the researchers wrote.

“Most ototoxicity was grade 3 or 4 (90%) and bilateral (90%), which underscored its potential impact on quality of life,” the investigators noted. “Because damage to either hearing or vision reduces quality of life, partial or total loss of both senses could synergistically impair development, cognition, and rehabilitation, especially in young children. Hence, ototoxicity is a crucial issue in patients with bilateral retinoblastoma.”

Task Force Recommendations

The authors noted that carboplatin “is the principal agent in all retinoblastoma chemotherapy protocols reported to date.” Although considerably less toxic than cisplatin, carboplatin “has been linked to sensorineural hearing loss.” They also pointed out that the Children’s Oncology Group (COG) published recommendations for evaluating and managing pediatric patients at risk for hearing loss due to disease or its treatment. “The COG task force recommended that childhood cancer survivors should receive at least yearly hearing tests. More frequent testing is required if any change is noticed or if hearing loss is suspected,” the authors stated.

Of the 60 patients whose records were reviewed, 23 had been treated according to the Retinoblastoma-3 (RTE-3) protocol at St. Jude Children’s Research Hospital in Memphis. That protocol consisted of eight cycles of vincristine and carboplatin administered at 3-week intervals. After the RET-3 protocol closed, patients were treated off-protocol according to best clinical management, with 31 receiving carboplatin and vincristine, 5 also receiving etoposide, and 1 also receiving topetecan. The median number of audiologic evaluations was five per patient. Ototoxicity was evaluated by three different grading systems, which, the authors noted, “showed good overall agreement in the identification of patients with ototoxicity.” ■

Qaddoumi I, et al: J Clin Oncol 30:1034-1041, 2012.


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