Shirao Kuniaki, Matsumura Yasuhiro, Yamada Yasuhide, Muro Kei, Gotoh Masahiro, Boku Narikazu, Ohtsu Atsushi, Nagashima Fumio, Sano Yasushi, Mutoh Manabu, Tanigawara Yusuke
Gastrointestinal Oncology Division, National Cancer Center Hospital, Chuo-ku, Tokyo, 104-0045, Japan.
Jpn J Clin Oncol. 2006 May;36(5):295-300. doi: 10.1093/jjco/hyl016. Epub 2006 May 15.
Oxaliplatin, a platinum compound, has been commonly used around the world for treating advanced colorectal cancer. The generally recommended dose and schedule of oxaliplatin monotherapy is 130 mg/m(2) every 3 weeks. This trial was conducted to evaluate the safety and pharmacokinetics of oxaliplatin monotherapy in Japanese patients with solid tumors.
Oxaliplatin was administered as a 2-h intravenous infusion every 3 weeks at a dose of 90 and 130 mg/m(2). Blood was collected to determine the total platinum and the ultrafiltrate platinum concentrations in plasma in all cycles.
Nine patients were enrolled; three were given oxaliplatin monotherapy at 90 mg/m(2) and six received 130 mg/m(2). All tumors were colorectal cancer. The major adverse reactions included myelosuppressive, neurological and gastrointestinal toxicities, although most were grades 1 and 2 at both dose levels. Peripheral sensory neuropathy of without movement disturbance (grade 1 or 2) was observed in all patients at both dose levels. The 130 mg/m(2) dose level was not found to be the maximum tolerated dose, but was judged to be the recommended dose. No objective responses were seen and five cases of no change were observed. A bi-exponential open model best described the disappearance of platinum in the plasma, and a tri-exponential open model best described the disappearance of ultrafilterable platinum in the plasma at both dose levels. No racial difference was suggested in the pharmacokinetics of oxaliplatin.
The oxaliplatin monotherapy dose schedule of 130 mg/m(2) every 3 weeks, recommended worldwide, is acceptable for Japanese patients.
奥沙利铂是一种铂类化合物，在全球范围内广泛用于治疗晚期结直肠癌。奥沙利铂单药治疗的一般推荐剂量和方案是每3周130mg/m²。本试验旨在评估奥沙利铂单药治疗在日本实体瘤患者中的安全性和药代动力学。
奥沙利铂每3周静脉输注2小时，剂量分别为90mg/m²和130mg/m²。在所有周期中采集血样以测定血浆中总铂和超滤铂浓度。
共纳入9例患者；3例接受90mg/m²的奥沙利铂单药治疗，6例接受130mg/m²。所有肿瘤均为结直肠癌。主要不良反应包括骨髓抑制、神经毒性和胃肠道毒性，不过在两个剂量水平上大多数为1级和2级。在两个剂量水平的所有患者中均观察到无运动障碍的周围感觉神经病变（1级或2级）。未发现130mg/m²剂量水平是最大耐受剂量，但被判定为推荐剂量。未观察到客观缓解，观察到5例病情无变化。双指数开放模型最能描述血浆中铂的清除情况，三指数开放模型最能描述两个剂量水平下血浆中超滤铂的清除情况。未提示奥沙利铂药代动力学存在种族差异。
全球推荐的每3周130mg/m²奥沙利铂单药治疗方案对日本患者是可接受的。
