Evaluation of the effect of pentoxifylline on the prevention of paclitaxel‑induced peripheral neuropathy in breast cancer patients: a randomized controlled study

IF 3.4 Q2 PHARMACOLOGY & PHARMACY

Future Journal of Pharmaceutical Sciences Pub Date : 2024-10-07 DOI:10.1186/s43094-024-00691-5

Sondos S. Saleh, Diaa Eldin Moussa Sherif, Nagwa A. Sabri, May A. Shawki

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引用次数: 0

Abstract

Background

Paclitaxel-induced peripheral neuropathy (PIPN) is one of the most common and debilitating toxicity. Up till now, no treatment or preventive medication is recommended by guidelines. Pentoxifylline has been found to prevent PIPN in animal models. This study aimed to evaluate the tolerability and efficacy of pentoxifylline in preventing PIPN. To our knowledge, this is the first clinical trial to evaluate the potential effect of pentoxifylline on the prevention of PIPN in breast cancer (BC) patients.

Results

A simple-randomized placebo-controlled study was conducted on 60 BC patients receiving weekly paclitaxel and either pentoxifylline 400 mg twice daily (n = 30) or placebo (n = 30) for 12 weeks. Only 55 patients completed the study. The main objective was the evaluation of the effect of pentoxifylline on the incidence of PIPN which revealed no significant difference between the pentoxifylline group (85%) and the placebo group (100%). Secondary objectives included time to develop grade 2 or 3 (TTG 2/3) PIPN, the patient’s quality of life (QOL), serum tumor necrosis factor-α (TNF-α) and malondialdehyde and the tolerability of pentoxifylline. The median TTG 2/3 PIPN was not reached in the pentoxifylline group compared to 77 days (95% confidence interval of 70.91 to 83.07) in the placebo group. However, the difference did not reach significance. The assessment of the impact of PIPN on QOL was performed at baseline and at weeks 4, 8 and 12 using Functional Assessment of Cancer Therapy/Gynecologic Oncology Group-Neurotoxicity (FACT/GOG-NTX) subscale. The magnitude of the worsening in the QOL was significantly lower in the pentoxifylline group than in the placebo group at weeks 4, 8, and 12 (p values = 0.028, 0.003, and 0.018, respectively). Analysis of the serum TNF-α and malondialdehyde revealed no significant differences between the groups. Pentoxifylline was safe, tolerable and did not affect paclitaxel toxicity.

Conclusion

Oral pentoxifylline (400 mg twice daily) did not decrease the incidence of PIPN. However, it improved patients’ QOL significantly.

Trial registration Clinical Trials.gov, NCT05189535. Registered 4 October 2021, https://classic.clinicaltrials.gov/ct2/show/NCT05189535.

查看原文本刊更多论文

评估喷托非韦林对预防紫杉醇诱发的乳腺癌患者周围神经病变的作用：一项随机对照研究

背景紫杉醇诱发的周围神经病变（PIPN）是最常见、最令人衰弱的毒性反应之一。迄今为止，指南尚未推荐任何治疗或预防药物。在动物模型中发现，五氧去氧肾上腺素可预防 PIPN。本研究旨在评估喷托非韦林预防 PIPN 的耐受性和疗效。据我们所知，这是首次评估喷托非韦林对预防乳腺癌（BC）患者 PIPN 潜在作用的临床试验。结果对 60 名 BC 患者进行了一项简单的随机安慰剂对照研究，这些患者每周接受紫杉醇和喷托非韦林 400 毫克，每天两次（n = 30）或安慰剂（n = 30），为期 12 周。只有 55 名患者完成了研究。主要目标是评估喷托非利宁对 PIPN 发生率的影响，结果显示喷托非利宁组（85%）与安慰剂组（100%）之间无显著差异。次要目标包括发生 2 级或 3 级（TTG 2/3）PIPN 的时间、患者的生活质量（QOL）、血清肿瘤坏死因子-α（TNF-α）和丙二醛以及喷托非利兰的耐受性。与安慰剂组的 77 天（95% 置信区间为 70.91 至 83.07）相比，喷托非利兰组未达到中位 TTG 2/3 PIPN。然而，这一差异并不显著。在基线和第4、8、12周时，使用癌症治疗功能评估/妇科肿瘤组-神经毒性（FACT/GOG-NTX）分量表评估了PIPN对QOL的影响。在第4、8和12周时，喷托非利兰组的QOL恶化程度明显低于安慰剂组（P值分别为0.028、0.003和0.018）。对血清 TNF-α 和丙二醛的分析表明，各组之间没有显著差异。结论口服五氧化锡（400 毫克，每天两次）并不能降低 PIPN 的发生率。试验注册 Clinical Trials.gov，NCT05189535。2021年10月4日注册，https://classic.clinicaltrials.gov/ct2/show/NCT05189535。

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来源期刊

Future Journal of Pharmaceutical Sciences PHARMACOLOGY & PHARMACY-

自引率

0.00%

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审稿时长

23 weeks

期刊介绍： Future Journal of Pharmaceutical Sciences (FJPS) is the official journal of the Future University in Egypt. It is a peer-reviewed, open access journal which publishes original research articles, review articles and case studies on all aspects of pharmaceutical sciences and technologies, pharmacy practice and related clinical aspects, and pharmacy education. The journal publishes articles covering developments in drug absorption and metabolism, pharmacokinetics and dynamics, drug delivery systems, drug targeting and nano-technology. It also covers development of new systems, methods and techniques in pharmacy education and practice. The scope of the journal also extends to cover advancements in toxicology, cell and molecular biology, biomedical research, clinical and pharmaceutical microbiology, pharmaceutical biotechnology, medicinal chemistry, phytochemistry and nutraceuticals.