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

本研究的目的是确定吉西他滨的最大耐受剂量，每周输注30分钟，连续三周，然后休息一周；确定吉西他滨的毒性；测定吉西他滨在男女患者中的药动学行为；并在I期研究范围内确定吉西他滨的抗肿瘤活性。该研究于1996年7月对患者开放。15名符合条件的患者接受了27个疗程：6名患者每周1000mg /m2乘以3,7名患者每周1200mg /m2乘以3。每个药物水平均有一名患者接受了化疗和放疗的大量预处理。他们经历了4级骨髓抑制，没有接受第三次剂量。另一名1200mg /m2剂量水平的患者出现了3级LFT异常，因此保留了一次剂量，并以较低剂量给予第三次剂量3。骨髓抑制的报道与预期一致；1000mg /m2时，4级毒性为3例白细胞减少，2例血小板减少。这些是短暂的，在每周1000mg /m2 × 3的6例患者中，只有1例出现剂量限制性毒性。在1200mg /m2时，7名患者中有2名无法评估，1名过早。4级中性粒细胞减少症未见报道，仅有1例患者有4级血小板减少症。剂量限制性毒性尚未见报道。未来的计划是继续对女孩和男孩进行药代动力学采样，看看是否可以证实在成人中发现的性别差异。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.