Cisplatin, one of the most ototoxic anti-neoplastic agents, causes permanent hearing loss in up to 90% of patients. We assessed ototoxicity rates and prospectively collected audiologic outcomes of patients receiving low-dose or high-dose cisplatin with concurrent cochlear-sparing intensity-modulated radiation therapy (IMRT). Patients with head and neck squamous cell carcinoma (HNSCC) receiving definitive or adjuvant cisplatin-based chemoradiotherapy (CRT) were analyzed. Cisplatin was administered either in low doses weekly (40 mg/m2) for up to seven doses or in high doses triweekly (100 mg/m2) for up to three doses. Cochlear-sparing IMRT was delivered in all cases. Audiologic data were prospectively collected before, during, and after treatment completion. The primary endpoint was a hearing change grade of ≥3 after CRT completion. Of the 96 HNSCC patients evaluated, 69 received weekly cisplatin and 58 received definitive CRT. Of patients receiving weekly cisplatin, 13% developed ≥G3 ototoxicity vs. 56% of patients who received triweekly cisplatin (p< 0.001). In multivariable modeling, the cisplatin dose schedule remained significant (OR: 8.4, 95%CI: 2.8–27.8,p< 0.001) for risk of severe irreversible ototoxicity. Triweekly cisplatin CRT significantly increased the ≥G3 severe irreversible ototoxicity risk compared to low-dose weekly cisplatin, irrespective of the cumulative cisplatin dose, even with the use of cochlear-sparing IMRT. No significant difference in oncologic outcomes was observed between the two schedules.
顺铂作为耳毒性最强的抗肿瘤药物之一，可导致高达90%的患者发生永久性听力损失。本研究评估了接受低剂量或高剂量顺铂联合耳蜗保护性调强放疗（IMRT）患者的耳毒性发生率，并前瞻性收集其听力学结果。研究对象为接受根治性或辅助性顺铂放化疗的头颈部鳞状细胞癌（HNSCC）患者。顺铂给药方案分为低剂量周疗（40 mg/m²，最多7次）和高剂量三周疗法（100 mg/m²，最多3次）。所有病例均采用耳蜗保护性IMRT技术。听力学数据在治疗前、治疗期间及治疗结束后进行前瞻性收集。主要终点为放化疗结束后听力变化≥3级。在纳入评估的96例HNSCC患者中，69例接受周疗顺铂，58例接受根治性放化疗。周疗顺铂组13%患者出现≥3级耳毒性，而三周疗法组这一比例达56%（p<0.001）。多变量模型分析显示，顺铂给药方案对严重不可逆耳毒性风险具有显著影响（OR：8.4，95%CI：2.8–27.8，p<0.001）。即使在使用耳蜗保护性IMRT技术的情况下，与低剂量周疗方案相比，三周疗法顺铂放化疗显著增加≥3级严重不可逆耳毒性风险，且该风险与顺铂累积剂量无关。两种给药方案在肿瘤学结局方面未见显著差异。
肿瘤(癌症)患者之家