PHASE-I CLINICAL-TRIAL OF ORMAPLATIN (TETRAPLATIN, NSC-363812)
PHASE-I CLINICAL-TRIAL OF ORMAPLATIN (TETRAPLATIN, NSC-363812)
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DOI：
10.1097/00001813-199410000-00002
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发表时间：
1994-10-01
影响因子：
2.3
通讯作者：
VONHOFF, DD
中科院分区：
文献类型：
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作者：
OROURKE, TJ;WEISS, GR;VONHOFF, DD
奥马铂是一种铂类似物，因其毒性特征改变以及在体外和体内模型中对顺铂无交叉耐药性而开发。为了确定每天五次服用奥马铂的毒性和最大耐受剂量，难治性实体瘤患者连续五天接受奥马铂治疗，剂量范围为 1.0 至 15.0 mg/m(2)/天，共九个剂量水平。共有 35 名患者接受了 70 个周期的治疗。恶心、呕吐和骨髓抑制为中度且不限制剂量。在接受累积剂量大于或等于 165 mg/m(2) 的所有 5 名患者中均观察到剂量限制性神经毒性，包括感觉周围神经病变。这种神经毒性在所有患者中都有症状，并导致四名患者出现明显的功能障碍，其中两名患者无法行走。对一名患者在 13.0 mg/m(2)/天剂量水平下进行的灵敏原子吸收光谱分析显示，游离铂的 Cp(max) 为 163 ng/ml，t(1/2) 为 10.9 分钟。由于周围神经病变在低累积剂量而非绝对剂量水平下发生，因此无法确定 II 期剂量。
Ormaplatin is a platinum analog that was developed because of an altered toxicity profile and non-cross resistance to cisplatin in both in vitro and in vivo models. To determine the toxicities and maximum tolerated dose of ormaplatin on a daily times five schedule, patients with refractory solid tumors received ormaplatin on five consecutive days at nine dose levels ranging from 1.0 to 15.0 mg/m(2)/day. A total of 35 patients received 70 cycles of therapy. Nausea and vomiting and myelosuppression were moderate and not dose-limiting. Dose-limiting neurotoxicity, consisting of a sensory peripheral neuropathy, was seen in all five patients who received cumulative doses greater than or equal to 165 mg/m(2). This neurotoxicity was symptomatic in all patients and caused significant functional impairment in four patients with inability to walk in two patients. A sensitive atomic absorption spectroscopy analysis performed for one patient at the 13.0 mg/m(2)/day dose level showed a Cp(max) of 163 ng/ml and a t(1/2) of 10.9 min for free platinum. A phase II dose could not be determined due to the onset of peripheral neuropathy at low cumulative doses and not at absolute dose levels.