COAST (Cisplatin ototoxicity attenuated by aspirin trial): A phase II double-blind, randomised controlled trial to establish if aspirin reduces cisplatin induced hearing-loss.
COAST (Cisplatin ototoxicity attenuated by aspirin trial): A phase II double-blind, randomised controlled trial to establish if aspirin reduces cisplatin induced hearing-loss.
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DOI：
10.1016/j.ejca.2017.09.033
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发表时间：
2017-12
期刊：
影响因子：
--
通讯作者：
King E
中科院分区：
文献类型：
--
作者：
Crabb SJ;Martin K;Abab J;Ratcliffe I;Thornton R;Lineton B;Ellis M;Moody R;Stanton L;Galanopoulou A;Maishman T;Geldart T;Bayne M;Davies J;Lamb C;Popat S;Joffe JK;Nutting C;Chester J;Hartley A;Thomas G;Ottensmeier C;Huddart R;King E
顺铂是最具耳毒性的化疗药物之一，导致高达50%的患者永久性和不可逆性听力损失。顺铂和庆大霉素被认为通过一种共同的机制损害听力，涉及内耳中的活性氧。阿司匹林已被证明可以最大限度地减少庆大霉素诱导的耳毒性。因此，我们验证了阿司匹林也可以减少顺铂化疗引起的耳毒性的假设。一项II期、双盲、安慰剂对照试验共招募了94例接受基于顺铂的化疗治疗多种癌症类型的患者，并以1：1的比例随机分配至接受阿司匹林975 mg tid和奥美拉唑20 mg od，或在每个治疗周期中从顺铂给药前一天至给药后2天接受匹配的安慰剂。患者在顺铂末次给药前、给药后7天和90天进行纯音测听。主要终点是双耳的联合听力损失（cHL），即6 kHz和8 kHz的听力损失总和。虽然阿司匹林耐受性良好，但它不能保护接受顺铂的患者的听力（p值= 0.233，20%单侧显著性水平）。在阿司匹林组中，顺铂治疗后患者的平均cHL为49 dB（标准差[SD] 61.41），而安慰剂组患者的平均cHL为36 dB（SD 50.85）。女性的平均听力损失高于男性，接受头颈部恶性肿瘤治疗的患者的cHL最严重。阿司匹林不能预防顺铂相关的耳毒性。因此，顺铂和庆大霉素可能具有不同的耳毒性机制，或者顺铂诱导的耳毒性可能对此处使用的阿司匹林方案无效。阿司匹林耐受性良好。阿司匹林在这里研究的剂量和时间表中没有保护听力。顺铂和庆大霉素可能具有不同的耳毒性机制。定性数据表明阿司匹林具有保护作用，但假设效力较低。顺铂诱导的耳毒性导致显著的发病率。
Cisplatin is one of the most ototoxic chemotherapy drugs, resulting in a permanent and irreversible hearing loss in up to 50% of patients. Cisplatin and gentamicin are thought to damage hearing through a common mechanism, involving reactive oxygen species in the inner ear. Aspirin has been shown to minimise gentamicin-induced ototoxicity. We, therefore, tested the hypothesis that aspirin could also reduce ototoxicity from cisplatin-based chemotherapy. A total of 94 patients receiving cisplatin-based chemotherapy for multiple cancer types were recruited into a phase II, double-blind, placebo-controlled trial and randomised in a ratio of 1:1 to receive aspirin 975 mg tid and omeprazole 20 mg od, or matched placebos from the day before, to 2 days after, their cisplatin dose(s), for each treatment cycle. Patients underwent pure tone audiometry before and at 7 and 90 days after their final cisplatin dose. The primary end-point was combined hearing loss (cHL), the summed hearing loss at 6 kHz and 8 kHz, in both ears. Although aspirin was well tolerated, it did not protect hearing in patients receiving cisplatin (p-value = 0.233, 20% one-sided level of significance). In the aspirin arm, patients demonstrated mean cHL of 49 dB (standard deviation [SD] 61.41) following cisplatin compared with placebo patients who demonstrated mean cHL of 36 dB (SD 50.85). Women had greater average hearing loss than men, and patients treated for head and neck malignancy experienced the greatest cHL. Aspirin did not protect from cisplatin-related ototoxicity. Cisplatin and gentamicin may therefore have distinct ototoxic mechanisms, or cisplatin-induced ototoxicity may be refractory to the aspirin regimen used here. Aspirin was well tolerated. Aspirin did not protect hearing at the doses and in the schedule investigated here. Cisplatin and gentamicin may have distinct ototoxic mechanisms. Qualitative data suggest protective aspirin effect but low power for hypothesis. Cisplatin-induced ototoxicity results in significant morbidity.
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DOI：
10.1097/00000421-199906000-00020
发表时间：
1999-06-01
影响因子：
2.6
作者：
Nagy, JL;Adelstein, DJ;Lavertu, P
通讯作者：
Lavertu, P
影响因子：
2.6
作者：
Kirkim, Gunay;Olgun, Yuksel;Ellidokuz, Hulya
通讯作者：
Ellidokuz, Hulya
影响因子：
4.7
作者：
Thornton, ARD;Shin, K;Hine, J
通讯作者：
Hine, J
影响因子：
4.6
作者：
Callejo A;Sedó-Cabezón L;Juan ID;Llorens J
通讯作者：
Llorens J
影响因子：
2.5
作者：
ANNIKO, M;SOBIN, A
通讯作者：
SOBIN, A