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

吉西他滨 (NSC) 的儿科研究

• 批准号: 6264950
• 负责人: CAROLA AS ARNDT
• 金额: $ 2.01万
• 依托单位: MAYO CLINIC ROCHESTER
• 依托单位国家: 美国
• 财政年份: 1998
• 资助国家: 美国
• 起止时间: 1998-12-01 至 1999-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6264950
• 关键词: clinical research; clinical trial phase I; dosage; gemcitabine; gender difference; human subject; human therapy evaluation; neoplasm /cancer; neoplasm /cancer chemotherapy; pediatric neoplasm /cancer; pharmacokinetics

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.

本研究的目标是确定吉西他滨的最大耐受剂量，每周输注 30 分钟，持续三周，然后休息一周；确定本表中给予吉西他滨的毒性；确定吉西他滨在男性和女性患者中的药代动力学行为；并确定吉西他滨在 I 期研究范围内的抗肿瘤活性。该研究于 1996 年 7 月向患者开放。15 名符合条件的患者接受了 27 个疗程：6 名患者接受 1000 mg/m2 每周 3 次治疗，7 名患者接受 1200 mg/m2 每周 3 次治疗。每个药物水平都有一名患者接受过大量化疗和放疗预处理。 他们经历了 4 级骨髓抑制，并且没有接受第三剂。另一名患者在 1200 mg/m2 剂量水平下出现 3 级 LFT 异常，因此保留了一个剂量，并以较低剂量给予了第三个剂量3。正如预期的那样，报告了骨髓抑制； 1000 mg/m2 时，4 级毒性为三名患者出现白细胞减少症，两名患者出现血小板减少症。 这些都是暂时的，每周 1000 mg/m2 次 3 的六名患者中只有一名出现剂量限制性毒性。 在 1200 mg/m2 时，七名患者中有两名无法评估，一名还为时过早。 尚未报道 4 级中性粒细胞减少症，只有 1 名患者出现 4 级血小板减少症。尚未报道剂量限制性毒性。未来的计划是继续对女孩和男孩进行药代动力学采样，看看是否可以证实成人中发现的性别差异。 该研究很可能会探索下一个药物水平。