PEDIATRIC STUDY OF GEMCITABINE (NSC#613327) IN SOLID TUMORS

这项研究的目标是确定吉西他滨的最大耐受量，即每周30分钟的输液，然后休息一周；确定按此时间表给予的吉西他滨的毒性；确定吉西他滨在男性和女性患者中的药代动力学行为；并在I期研究的范围内确定吉西他滨的抗肿瘤活性。这项研究于1996年7月向患者开放。15例符合条件的患者接受27个疗程：6例1000 mg/m2，每周3次，7例1200 mg/m2，每周3次。每个药物水平均有1例患者接受了大量的化疗和放疗。他们经历了4级骨髓抑制，没有接受第三剂。另一名1200 mg/m2剂量水平的患者出现3级LFT异常，因此维持一次剂量，并以较低的剂量给予第三次剂量3。骨髓抑制的报道与预期不谋而合；在1000 mg/m2的剂量下，3名患者出现4级毒性反应，2名患者出现血小板减少。这些都是暂时性的，每周3次1000 mg/m2的6名患者中只有1人有剂量限制性毒性。在1200 mg/m2的剂量下，7名患者中有2名无法评估，1名为时过早。4级中性粒细胞减少症尚未见报道，仅有1例患者出现4级血小板减少症。剂量限制毒性尚未见报道。未来的计划是继续在女孩和男孩身上进行药代动力学抽样，看看在成年人中发现的性别差异是否可以得到证实。这项研究很可能会探索下一个药物水平。

The goals of this study are to determine the maximum tolerable dose of gemcitabine given as a 30-minute infusion weekly for three weeks followed by one week rest; to determine the toxicities of gemcitabine given on this schedule; to determine the pharmacokinetic behavior of gemcitabine in male and female patients; and to determine the antitumor activity of gemcitabine within the confines of a phase I study. The study was opened to patient entry in July 1996. Fifteen eligible patients have received 27 courses: 6 patients at 1000 mg/m2 weekly times 3 and 7 patients at 1200 mg/m2 weekly times 3. One patient at each drug level had been heavily pretreated with chemotherapy and radiotherapy. They experienced grade 4 myelosuppression and did not receive the third dose. Another patient at the 1200 mg/m2 dose level experienced grade 3 LFT abnormalities so a dose was held and a third dose3 was given at a lower dose. Myelosuppression has been reported as expected; at 1000 mg/m2, grade 4 toxicity was leukopenia in three patients, and thrombocytopenia in two patients. These are transient, only one of six patients at 1000 mg/m2 weekly times 3 had dose-limiting toxicity. At 1200 mg/m2, two of seven patients were not evaluable and one is too early. Grade 4 neutropenia has not been reported, and only one patient had grade 4 thrombocytopenia. Dose-limiting toxicity has not been reported. Future plans are to continue pharmacokinetic sampling on both girls and boys to see if sex differences found in adults can be confirmed. It is likely that the study will explore the next drug level.