Cassidy Jim, Misset Jean-Louis
Department of Medicine and Therapeutics, University of Aberdeen, Institute of Medical Sciences, Aberdeen, Scotland.
Semin Oncol. 2002 Oct;29(5 Suppl 15):11-20. doi: 10.1053/sonc.2002.35524.
Oxaliplatin is the only third-generation platinum derivative to have found a place in routine cancer therapy. It is particularly useful therapy for advanced colorectal cancer and has shown scheduling flexibility in combination with 5-fluorouracil/folinic acid. Oxaliplatin has a unique pattern of side effects unrelated to those observed with other therapeutic platinum derivatives. During the course of oxaliplatin clinical trials, the adverse events most often cited were hematologic toxicity, gastrointestinal tract toxicity, and a neurolopathy unlike that observed with other platinum derivatives. Grade 3/4 neutropenia occurred in 41.7% of patients in the phase III clinical trial that used the FOLFOX-4 regimen, and thrombocytopenia is a rare event sometimes observed after multiple cycles of therapy. Nausea and vomiting is usually mild to moderate and readily controlled with standard antiemetics. Grade 1/2 diarrhea may occur but studies have shown that 5-fluorouracil contributes significantly more to gastrointestinal toxicity than does single-agent oxaliplatin. Nephrotoxicity has not been reported in any of the oxaliplatin trials, allowing administration of oxaliplatin without hydration. Oxaliplatin-induced neurotoxicity consists of a rapid-onset acute sensory neuropathy and a late-onset cumulative sensory neuropathy that occurs after several cycles of therapy. In about three fourths of patients, neurotoxicity is reversible with a median time to recovery of 13 weeks after treatment discontinuation. To date, oxaliplatin has proven to be a safe and effective therapy for colorectal cancer and side effects have been easy to manage with appropriate awareness from patients and care providers.
奥沙利铂是唯一在常规癌症治疗中占有一席之地的第三代铂类衍生物。它对晚期结直肠癌特别有用，并且在与5-氟尿嘧啶/亚叶酸联合使用时显示出给药方案的灵活性。奥沙利铂具有独特的副作用模式，与其他治疗性铂类衍生物所观察到的副作用不同。在奥沙利铂的临床试验过程中，最常被提及的不良事件是血液学毒性、胃肠道毒性以及一种与其他铂类衍生物不同的神经病变。在使用FOLFOX-4方案的III期临床试验中，41.7%的患者出现3/4级中性粒细胞减少，血小板减少是在多个治疗周期后有时观察到的罕见事件。恶心和呕吐通常为轻至中度，用标准的止吐药很容易控制。可能会发生1/2级腹泻，但研究表明，5-氟尿嘧啶对胃肠道毒性的影响比单药奥沙利铂大得多。在任何奥沙利铂试验中均未报告肾毒性，因此使用奥沙利铂时无需水化。奥沙利铂引起的神经毒性包括快速发作的急性感觉神经病变和在几个治疗周期后出现的迟发性累积感觉神经病变。在大约四分之三的患者中，神经毒性是可逆的，停药后恢复的中位时间为13周。迄今为止，奥沙利铂已被证明是一种安全有效的结直肠癌治疗方法，并且在患者和医护人员有适当认识的情况下，副作用很容易处理。
