Kitade Hironori, Shimasaki Takeo, Igarashi Saya, Sakuma Hiroshi, Mori Mitsue, Tomosugi Naohisa, Nakai Masuo
Department of Pharmacy, Houju Memorial Hospital, Nomi, Ishikawa 923-1226, Japan.
Outpatient Cancer Chemotherapy Center, Houju Memorial Hospital, Nomi, Ishikawa 923-1226, Japan ; Medicalm Research Institute, Kanazawa Medical University, Kahoku, Ishikawa 920-0293, Japan.
Oncol Lett. 2014 May;7(5):1499-1502. doi: 10.3892/ol.2014.1890. Epub 2014 Feb 18.
Neurotoxicity is one of the most frequent side-effects of oxaliplatin. Oxaliplatin-induced cumulative and dose-limiting neurotoxicity either results in dose reduction or decreases the patients' quality of life. However, the symptoms of neurotoxicity often vary among patients. The current study presents the case of a male with rectal cancer, who was administered a cumulative oxaliplatin dose of >5,000 mg/m without developing neurotoxicity or allergic reactions. Consequently, this patient continued therapy with modified 5-fluorouracil, leucovorin and oxaliplatin treatment for four years, with stabilization of the disease. This case indicates that if oxaliplatin-containing chemotherapy shows efficacy with no toxicity, the long-term administration of oxaliplatin would be effective and tolerable. Previously, the analysis of genomic polymorphisms in drug target genes has been important for explaining interindividual variations in the efficacy and toxicity of anti-cancer drugs. In the present patient, the glutathione S-transferase P1 (GSTP1) gene polymorphism, which is involved in the detoxification of platinum drugs, was analyzed. The genotype of the present case has been revealed as wild type (Ile/Ile) genotype. In addition, the associations between oxaliplatin-induced neurotoxicity and the GSTP1 polymorphism were also assessed. Certain studies have demonstrated that oxaliplatin-induced neurotoxicity occurs more frequently in patients with the Ile/Ile genotype, while others have demonstrated that those patients with the Val/Val or Ile/Val genotypes are more likely to develop neurotoxicity. Therefore, correlation between the GSTP1 polymorphism and oxaliplatin-induced neurotoxicity remains controversial. Overall, further development of individualized chemotherapy with an analysis of genomic polymorphisms in the drug target genes is required for the prophylaxis oxaliplatin-induced neurotoxicity.
神经毒性是奥沙利铂最常见的副作用之一。奥沙利铂诱导的累积性和剂量限制性神经毒性会导致剂量减少或降低患者的生活质量。然而，神经毒性症状在患者中往往各不相同。本研究报告了一例直肠癌男性患者，其接受的奥沙利铂累积剂量>5000mg/m²，却未出现神经毒性或过敏反应。因此，该患者继续接受改良的5-氟尿嘧啶、亚叶酸钙和奥沙利铂治疗四年，病情稳定。该病例表明，如果含奥沙利铂的化疗显示出疗效且无毒性，长期使用奥沙利铂将是有效且可耐受的。此前，分析药物靶基因中的基因组多态性对于解释抗癌药物疗效和毒性的个体差异很重要。在本患者中，分析了参与铂类药物解毒的谷胱甘肽S-转移酶P1（GSTP1）基因多态性。本病例的基因型已被鉴定为野生型（Ile/Ile）基因型。此外，还评估了奥沙利铂诱导的神经毒性与GSTP1多态性之间的关联。某些研究表明，奥沙利铂诱导的神经毒性在Ile/Ile基因型患者中更频繁发生，而其他研究则表明，Val/Val或Ile/Val基因型的患者更易发生神经毒性。因此，GSTP1多态性与奥沙利铂诱导的神经毒性之间的相关性仍存在争议。总体而言，需要通过分析药物靶基因中的基因组多态性来进一步发展个体化化疗，以预防奥沙利铂诱导的神经毒性。
