The effects of sodium thiosulfate (STS) on cisplatin-induced hearing loss: A report from the Children’s Oncology Group.
2014; Lippincott Williams & Wilkins; Volume: 32; Issue: 15_suppl Linguagem: Inglês
10.1200/jco.2014.32.15_suppl.10017
ISSN1527-7755
Autores Tópico(s)Brain Metastases and Treatment
Resumo10017 Background: Cisplatin frequently causes irreversible hearing loss in children treated for cancer. STS is a thiol reducing agent shown in preclinical studies to protect hearing but not the tumor with its timed administration post-cisplatin. Methods: The primary aim of ACCL0431 was to evaluate the efficacy of STS, compared with observation (Obs), for preventing cisplatin-induced hearing loss. Eligible subjects were 1–18 years old with normal audiometry and planned cisplatin infusions of ≤ 6 hours with cumulative dose ≥ 200 mg/m2. Subjects were randomized either to Obs or treatment with STS 16 grams/m2 IV over 15 minutes 6 hours after each cisplatin dose. Hearing was measured using standard audiometry for age; data were reviewed centrally using American Speech-Language-Hearing Association criteria. The proportion of subjects with hearing loss (χ2 test) assessed at 4 weeks post the final cisplatin dose (primary endpoint) and EFS/OS (log-rank test, 2-year cumulative estimates and Cox proportional hazards model) were compared between the two groups. Results: 126 eligible subjects were enrolled with germ cell tumor (32), osteosarcoma (30), neuroblastoma (26), medulloblastoma (26), hepatoblastoma (7) or other (5). 105 subjects (64 male, 30 <5 years old) were evaluable for the primary aim. The proportion of hearing loss for STS vs. Obs was 28.6% vs. 55.4%, respectively (p=0.006). Including all 126 subjects at median post-diagnosis follow-up of 2.1 years, EFS for STS vs. Obs was 60.1% vs. 70.0% (p=0.53); OS was 74.5% vs. 88.8% (p=0.050). Subset analysis by extent of disease (determined post hoc) was performed. For subjects with localized disease, EFS was 72.5% vs. 67.1% (p=0.61); HR (hazard ratio) 0.81 (p=0.61); OS was 89.7% vs. 89.2% (p=0.73); HR 1.26 (p=0.73). For those with disseminated disease, EFS was 35.8% vs. 75.0% (p=0.047); HR 2.51 (p=0.055); OS was 49.0% vs. 88.3% (p=0.010); HR 4.03 (p=0.017). Conclusions: STS protects against cisplatin-induced hearing loss in children. However, the potentially lower survival seen in those with disseminated disease receiving STS raises the concern of a tumor protective effect when the drug is administered on this dose and schedule. Clinical trial information: NCT00716976.
Referência(s)