Hayashi Robert J, Blaney Susan, Sullivan Jim, Weitman Steve, Vietti Teresa, Bernstein Mark L
University School of Medicine, Division of Pediatric Hematology/Oncology, Box 8116, 660 South Euclid, St. Louis, MO 63110, USA.
J Pediatr Hematol Oncol. 2003 Jul;25(7):539-42. doi: 10.1097/00043426-200307000-00008.
To perform a phase 1 trial to determine the maximum tolerated dose and the dose-limiting toxicities of paclitaxel in children with refractory or recurrent solid tumors. Paclitaxel was administered twice weekly, increasing from four to six doses every 21 to 28 days.
Paclitaxel was administered as a 3-hour intravenous infusion twice weekly. The initial dose was fixed at 50 mg/m2/dose twice weekly for 2 weeks (four doses), every 21 days. The number of twice-weekly doses per course was increased to six in the next cohort. In subsequent cohorts, the number of twice-weekly doses per course was fixed at six, every 28 days, and dosage was increased in 25% increments.
Sixteen assessable patients were enrolled at three levels. Neutropenia was the dose-limiting toxicity at 65 mg/m2/dose, twice weekly x 6 doses, every 28 days. Nonhematologic toxicities were minor. No antitumor responses were observed.
Protracted twice-weekly dosing of paclitaxel is limited by neutropenia. The maximum tolerated dose of paclitaxel administered twice weekly x 6 doses, every 28 days, was 50 mg/m2/dose.
开展一项1期试验，以确定紫杉醇在难治性或复发性实体瘤儿童患者中的最大耐受剂量和剂量限制性毒性。紫杉醇每周给药两次，每21至28天从4剂增加至6剂。
紫杉醇通过3小时静脉输注每周给药两次。初始剂量固定为每周两次，每次50mg/m²，共2周（4剂），每21天给药一次。在下一组中，每个疗程每周两次的给药次数增加至6次。在随后的组中，每个疗程每周两次的给药次数固定为6次，每28天给药一次，剂量以25%的幅度递增。
在三个剂量水平纳入了16例可评估患者。中性粒细胞减少是剂量限制性毒性，发生于每28天一次、每周两次、每次65mg/m²剂量时。非血液学毒性较轻。未观察到抗肿瘤反应。
紫杉醇每周两次的延长给药受中性粒细胞减少的限制。每28天一次、每周两次、每次6剂给药的紫杉醇最大耐受剂量为50mg/m²/剂量。
