Ototoxicity of cisplatin plus standard radiation therapy vs. accelerated radiation therapy in glioblastoma patients

Purpose : To assess the effect of cisplatin (CDDP) plus concurrent radiation therapy on hearing loss. Methods : 451 patients with glioblastoma multiforme (GBM) were randomly assigned after surgery to: Arm A: Carmustine (BCNU) + standard radiation therapy (SRT); Arm B: BCNU + accelerated radiation therapy (ART: 160 cGy twice daily for 15 days); Arm C: CDDP + BCNU + SRT; or Arm D: CDDP + BCNU + ART. Patients on arms C and D received audiograms at baseline, and prior to the start of RT, and prior to cycles 3 and 6. Otologic toxicities were recorded at each visit. Results : 56% of patients had hearing loss at baseline. 13% and 50% of patients experienced worsening ototoxicity after 1 year of treatment in arms A and B vs. C and D, respectively, with 13% of those on arms C and D experiencing significant ototoxicity (≥ grade 3) at 6 months. Increasing age was associated with an increased risk of ototoxicity. Conclusions : Increased exposure to CDDP increases the risk of ototoxicity over time. Older patients are more susceptible to hearing loss with CDDP. The low proportion of patients with clinically significant ototoxicity suggests that baseline screening is unnecessary in GBM patients.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/43476/1/11060_2005_Article_9049.pd

A North Central Cancer Treatment Group Phase II Trial of Topotecan in Relapsed Gliomas.

Current systemic treatment options for patients with relapsed gliomas are limited. The topoisomerase I inhibitor topotecan has demonstrated broad antitumor activity in both preclinical studies as well as a number of phase I and II trials in humans. Studies in primates have shown good cerebrospinal fluid levels of topotecan following systemic administration. We therefore performed this phase II trial in patients who developed evidence of progressive glioma after definitive radiation therapy. Patients were treated with 1.5 mg/m2 intravenously daily for 5 consecutive days repeated every three weeks. For patients who had received prior nitrosourea-containing chemotherapy, the starting dose was 1.25 mg/m2. Thirty-three patients were entered on this study. All patients were eligible and evaluable for both response and toxicity. Seven patients experienced grade 4 leukopenia with 2 of these patients dying of infection-related complications. Six of these seven patients were not taking anticonvulsants during treatment. Nine patients developed grade 3-4 thrombocytopenia, seven of whom were not taking anticonvulsants. Nonhematologic side effects were infrequent and manageable. One patient experienced a partial response to this treatment for an overall response rate of 3% (95% binomial confidence interval 0.3%-20.4%). The median time to progression was 14.9 weeks and median survival 19.9 weeks. Topotecan at this dose and schedule showed no substantial activity in relapsed gliomas

Figure e-2

Figure e-2. Depersonalization, emotional exhaustion, and personal accomplishment by weekend responsibilities and se

e-Supplement 2: e-Tables and Figure e-1 and e-2 Legends

e-Supplement 2: e-Tables and Figure e-1 and e-2 Legend