A randomized trial of topical menthol for chemotherapy induced neuropathy

描述（由申请人提供）：由于早期发现和治疗方面的重大进展，今天估计有1200万癌症幸存者生活在美国。不幸的是，大多数癌症疗法都有很大的长期副作用风险。化疗引起的周围神经病变（CIPN）是最常见和使人衰弱的不良反应之一，它与许多广泛使用的抗癌药物有关。对于持续性CIPN的最佳治疗方法尚不清楚。对症治疗包括抗抑郁药、抗惊厥药、非麻醉性和麻醉性镇痛药。虽然抗抑郁药显示出适度的益处，但由于副作用和显著的药物间相互作用，它们的使用受到限制。一些小的非盲法研究表明局部薄荷醇可能对缓解神经病变有益。我们假设，在紫杉烷或奥沙利铂为基础的辅助化疗方案后，使用每日两次的2%局部薄荷醇进行为期六周的治疗将减少持续的神经性疼痛。我们计划对乳腺癌和结肠癌患者进行辅助治疗后的两组双盲、安慰剂对照、随机试验研究来验证这一假设。我们的目的是(1)评估每日两次局部应用薄荷醇治疗6周是否会减少持续性神经性疼痛；(2)评价外用薄荷醇与安慰剂对神经病变整体指标的影响；(3)评价外用薄荷醇对客观感觉和运动功能测试的影响；(4)对治疗与化疗类型的相互作用进行探索性分析。到目前为止，我们还没有成功地治疗或预防CIPN。本研究评估了一种有前途的、容易获得的、低成本和耐受性良好的局部干预的使用。如果发现有效，这种治疗解决了CIPN的潜在机制，可能会使我们更接近于改善癌症幸存者的生活。

DESCRIPTION (provided by applicant): Due to major advances in early detection and therapy, an estimated 12 million cancer survivors are living in the United States today. Unfortunately, most cancer therapies are known to carry a substantial risk of adverse long-term effects. One of the most common and debilitating adverse effects is chemotherapy-induced peripheral neuropathy (CIPN), which is associated with many widely used anticancer drugs. The optimal treatment for persistent CIPN remains unknown. Symptomatic treatments include antidepressants, anticonvulsants, non-narcotic and narcotic analgesics. While antidepressants have shown moderate benefit, their use has been limited due to side effects and significant drug to drug interactions. A few small unblinded studies of topical menthol suggest a possible benefit in relieving neuropathy. We hypothesize that six week treatment with 2% topical Menthol application twice a day will decrease persistent neuropathic pain following adjuvant chemotherapy with a Taxane or Oxaliplatin-based regimen. We plan to test this hypothesis with a two arm double blind, placebo controlled, randomized pilot study following adjuvant therapy in breast and colon cancer patients. Our aims are (1) To assess whether six week treatment with twice daily topical Menthol application will decrease persistent neuropathic pain; (2) To evaluate the effect of topical Menthol compared to placebo on global measures of neuropathy; (3) To evaluate the effect of topical Menthol on objective sensory and motor functional tests; and (4) To perform an exploratory analysis evaluating the interaction between treatment and chemotherapy type. To date, we have not been successful at treating or preventing CIPN. This study evaluates the use of a promising and readily available, low cost and well tolerated topical intervention. If found beneficial, this treatment addressing the putative underlying mechanism of CIPN, may bring us one step closer to improving the lives of cancer survivors.