Extra J M, Marty M, Brienza S, Misset J L
Institut Curie, Paris, France.
Semin Oncol. 1998 Apr;25(2 Suppl 5):13-22.
In early clinical trials, oxaliplatin has demonstrated significant activity against colorectal cancer, both as a single agent and in combination with 5-fluorouracil (5-FU) and folinic acid (FA). Oxaliplatin differs from cisplatin in its lack of nephrotoxicity and from carboplatin in its hematologic toxicity being mild. The most constant acute side effect of oxaliplatin observed in clinical trials was a transient peripheral neuropathy manifesting as paresthesia and dysesthesia in the extremities, triggered or enhanced by exposure to cold. The neurosensory phenomena, dependent on the cumulative dose of oxaliplatin, affect all patients who receive doses > or = 540 mg/m2 over four cycles or more of therapy. This neurologic toxicity is also highly reversible, with 82% of patients having their neuropathy regress within 4 to 6 months and 41% experiencing complete recovery within 6 to 8 months. With these considerations in mind, the currently recommended dosing schedules for oxaliplatin are 130 mg/m2/d as a 2- to 6-hour infusion or 175 mg/m2/d as a chronomodulated infusion over 5 days, both of which are administered every 3 weeks. Oxaliplatin rapidly disappears from the plasma and is rapidly transformed into putative active species. 5-Fluorouracil and folinic acid, often used in combination with oxaliplatin, do not affect its pharmacokinetics. The favorable pharmacokinetics and safety profile of oxaliplatin contribute to its tolerability, particularly in pretreated cancer patients with reduced renal function. The reversible nature of its dose-limiting neurotoxicity and its synergistic action with 5-FU/FA make oxaliplatin an interesting agent for the treatment of colorectal cancer and for other potential indications.
在早期临床试验中，奥沙利铂已显示出对结直肠癌具有显著活性，无论是作为单一药物还是与5-氟尿嘧啶（5-FU）和亚叶酸（FA）联合使用。奥沙利铂与顺铂不同，它没有肾毒性；与卡铂不同，它的血液学毒性较轻。在临床试验中观察到的奥沙利铂最常见的急性副作用是短暂性周围神经病变，表现为肢体感觉异常和感觉迟钝，接触寒冷会引发或加重这种症状。这种神经感觉现象取决于奥沙利铂的累积剂量，会影响所有在四个周期或更多周期的治疗中接受剂量≥540mg/m²的患者。这种神经毒性也是高度可逆的，82%的患者在4至6个月内神经病变消退，41%的患者在6至8个月内完全恢复。考虑到这些因素，目前推荐的奥沙利铂给药方案为：130mg/m²/天，静脉滴注2至6小时；或175mg/m²/天，在5天内进行时间调节静脉滴注，两种方案均每3周给药一次。奥沙利铂迅速从血浆中消失，并迅速转化为假定的活性物质。经常与奥沙利铂联合使用的5-氟尿嘧啶和亚叶酸不会影响其药代动力学。奥沙利铂良好的药代动力学和安全性使其具有较好的耐受性，尤其是对于肾功能减退的经治癌症患者。其剂量限制性神经毒性的可逆性以及与5-FU/FA的协同作用，使奥沙利铂成为治疗结直肠癌及其他潜在适应证的有吸引力的药物。
