A Cautionary Tale: Dosing Chemotherapy in Infants With Retinoblastoma
Authors: Ann Leahey
Journal: Journal of Clinical Oncology (2012)

This year, 8,000 children will be diagnosed with retinoblastoma (RB) worldwide.This rare childhood cancer is a threat not only to sight but also to life.The majority of children diagnosed with RB live in economically underdeveloped countries where fewer than half can be expected to survive into adulthood. 1In contrast, in the United States, where only a few hundred children develop RB each year, almost all will be cured of RB. 2 Before the 1990s, treatment of intraocular RB consisted largely of surgery (enucleation) and external-beam radiotherapy (EBRT).These therapies cured patients and salvaged vision.However, late effects including severe orbital hypoplasia with attendant cosmetic deformity, 3 and a threefold increase in the rate of second tumors was found among children carrying the RB mutation. 4,5In the early 1990s, pediatric oncologists learned that certain chemotherapeutic agents, notably carboplatin and etoposide, were useful in the treatment of brain tumors.][8][9][10] The term chemoreduction refers to the use of chemotherapy to reduce tumor volume to allow successful treatment with focal ophthalmic therapies such as cryotherapy, thermotherapy, laser, and scleral radioactive plaques.The best results are obtained when experienced oncologic ophthalmologists provide focal therapy.In the article that accompanies this editorial, Qaddoumi et al 11 report their experience with carboplatin and vincristine in 60 patients with intraocular RB.In a retrospective review, they found an alarmingly high rate of sustained severe ototoxicity, a rate markedly different from three previously published reports from Dutch, 12 American, 13 and French investigators. 14Smits et al 12 reported their observations of the hearing status of 25 children with RB with a median age at initiation of treatment of 7 months and a median follow-up of 25 months.No hearing loss was detected except for a single patient with a 13q deletion who had severe hearing loss before treatment.Lambert et al 13 reported their data for 116 patients with intraocular RB who received carboplatin-containing regimens.The median age at the initiation of therapy was 10 months, and the median follow-up was 40 months.Again, no patient with a normal initial audiogram developed hearing loss.Of the 14 children with abnormal audiograms initially, only three remained persistently abnormal.Lastly, Jehanne et al 14 analyzed the data of 175 children with RB treated at the Institut Curie.The median age at diagnosis in this study was 4 months, and the median follow-up was 60 months.Although ototoxicity was found in eight children (one of whom had hearing loss before therapy), only two had hearing loss that required hearing aids.Jehanne et al concluded that ototoxicity was uncommon and might be associated with an as yet unpredictable individual susceptibility to carboplatin.Recently, specific genotypes associated with higher rates of cisplatin-induced hearing loss have been identified. 15ow does one reconcile the previous reports in which more than 300 young children were treated with carboplatin, without significant Editorials