Bokemeyer C, Berger C C, Hartmann J T, Kollmannsberger C, Schmoll H J, Kuczyk M A, Kanz L
Department of Hematology/Oncology/Immunology, Eberhard-Karls-University Medical Center II, Tübingen, Germany.
Br J Cancer. 1998 Apr;77(8):1355-62. doi: 10.1038/bjc.1998.226.
This study evaluates the degree and relevance of persisting ototoxicity after cisplatin-based standard-dose chemotherapy for testicular cancer, with emphasis on identification of potential factors for an increased risk of this late sequel. Hearing thresholds of 86 patients with a median age of 31 years (range 21-53 years) and a median follow-up time of 58 months (range 15-159 months) were assessed by conventional pure-tone audiometry. Interviews were conducted evaluating the patients' history with special regard to audiological risk factors, as well as circumstances of ototoxic symptoms. Details concerning treatment and patient variables were extracted retrospectively from the patients' charts. An additional screening programme assessed current body functions, blood parameters and other late toxicities. Symptomatic ototoxicity persisted in 20% of patients (59% tinnitus, 18% hearing loss, 23% both), while 10% had experienced completely reversible ototoxic symptoms for a duration of 1-18 months after treatment. Symptoms were bilateral in 81% of patients. Hearing thresholds were compatible with cisplatin-induced hearing loss in 42% of audiograms performed. Subjective (history) and objective (audiogram) findings were not always consistent. The following statistically significant risk factors for ototoxicity were established: high cumulative dose of cisplatin (P < 0.0001); history of noise exposure (P = 0.006). Additionally, high doses of vincristine (P = 0.001) seemed to result in reversible ototoxic symptoms. No other independent risk factors were identified. In conclusion, persisting ototoxicity represents a clinical sequel for approximately 20% of testicular cancer patients treated at standard dose but may affect more than 50% of patients receiving cumulative doses of cisplatin > 400 mg m(-2). Previous noise exposure may also result in a threefold increased risk for cisplatin ototoxicity. Future studies should use these risk factors as important stratification criteria for trials aiming at the evaluation and prevention of cisplatin-induced ototoxicity.
本研究评估了基于顺铂的标准剂量化疗治疗睾丸癌后持续性耳毒性的程度及相关性，重点在于识别这种晚期后遗症风险增加的潜在因素。通过传统纯音听力测定法评估了86例患者的听力阈值，这些患者的中位年龄为31岁（范围21 - 53岁），中位随访时间为58个月（范围15 - 159个月）。进行了访谈，评估患者病史，特别关注听力学危险因素以及耳毒性症状的情况。从患者病历中回顾性提取了有关治疗和患者变量的详细信息。另外一项筛查计划评估了当前身体功能、血液参数及其他晚期毒性。20%的患者存在症状性耳毒性（59%为耳鸣，18%为听力损失，23%两者皆有），而10%的患者在治疗后1 - 18个月经历了完全可逆的耳毒性症状。81%的患者症状为双侧性。在进行的42%的听力图中，听力阈值与顺铂诱导的听力损失相符。主观（病史）和客观（听力图）结果并不总是一致。确定了以下耳毒性的统计学显著危险因素：顺铂累积剂量高（P < 0.0001）；有噪声暴露史（P = 0.006）。此外，高剂量长春新碱（P = 0.001）似乎导致可逆性耳毒性症状。未识别出其他独立危险因素。总之，持续性耳毒性是约20%接受标准剂量治疗的睾丸癌患者的临床后遗症，但可能影响超过50%接受顺铂累积剂量> 400 mg m(-2)的患者。既往噪声暴露也可能使顺铂耳毒性风险增加两倍。未来研究应将这些危险因素用作旨在评估和预防顺铂诱导耳毒性试验的重要分层标准。
