BACKGROUND: This report summarizes a phase 1 study conducted by the Children's Cancer Group (CCG) to determine the maximum tolerated dose (MTD), dose-limiting toxicities (DLTs), pharmacokinetics, and anti-leukemia activity of paclitaxel in children with advanced stage leukemias. PROCEDURE: This study examined two dose escalation schedules of intravenous paclitaxel. Doses ranged from 250 to 500 mg/m(2) every 21 days in schedule A and 105 to 200 mg/m(2) weekly x 3 every 28 days in schedule B. Serial plasma samples for pharmacokinetic studies were obtained after the first paclitaxel dose. RESULTS: Sixty-three patients (median 10 years) with refractory or relapsed leukemia (ALL) (n = 39), acute myeloid leukemia (AML) (n = 19), biphenotypic (n = 4), and JCML (n = 1)) were enrolled. The DLTs in schedule A were grade 4 hypertension and hyperbilirubinemia with an MTD of 430 mg/m(2) every 21 days. The DLTs in schedule B were coagulopathy, hyperkalemia, hyperbilirubinemia, elevated SGOT (n = 1, 125 mg/m(2)), peripheral neuropathy (n = 1, 200 mg/m(2)), and typhlitis (n = 1, 200 mg/m(2)) with an MTD of 182 mg/m(2) weekly x 3 every 28 days. Among 54 evaluable patients, there was one complete response (CR), three partial responses (PR), and five patients with stable disease (SD). The mean terminal elimination half-life was 9.5 +/- 3.4 hr and the mean plasma clearance was 23 +/- 11 L/hr/m(2). CONCLUSIONS: Paclitaxel was tolerated at 430 mg/m(2) every 21 days and at 182 mg/m(2)/dose weekly x 3 every 28 days in pediatric patients. The objective response rate across all dose levels and schedules was <10%. (c) 2008 Wiley-Liss, Inc.
BACKGROUND: This report summarizes a phase 1 study conducted by the Children's Cancer Group (CCG) to determine the maximum tolerated dose (MTD), dose-limiting toxicities (DLTs), pharmacokinetics, and anti-leukemia activity of paclitaxel in children with advanced stage leukemias. PROCEDURE: This study examined two dose escalation schedules of intravenous paclitaxel. Doses ranged from 250 to 500 mg/m(2) every 21 days in schedule A and 105 to 200 mg/m(2) weekly x 3 every 28 days in schedule B. Serial plasma samples for pharmacokinetic studies were obtained after the first paclitaxel dose. RESULTS: Sixty-three patients (median 10 years) with refractory or relapsed leukemia (ALL) (n = 39), acute myeloid leukemia (AML) (n = 19), biphenotypic (n = 4), and JCML (n = 1)) were enrolled. The DLTs in schedule A were grade 4 hypertension and hyperbilirubinemia with an MTD of 430 mg/m(2) every 21 days. The DLTs in schedule B were coagulopathy, hyperkalemia, hyperbilirubinemia, elevated SGOT (n = 1, 125 mg/m(2)), peripheral neuropathy (n = 1, 200 mg/m(2)), and typhlitis (n = 1, 200 mg/m(2)) with an MTD of 182 mg/m(2) weekly x 3 every 28 days. Among 54 evaluable patients, there was one complete response (CR), three partial responses (PR), and five patients with stable disease (SD). The mean terminal elimination half-life was 9.5 +/- 3.4 hr and the mean plasma clearance was 23 +/- 11 L/hr/m(2). CONCLUSIONS:Paclitaxel was tolerated at 430 mg/m(2) every 21 days and at 182 mg/m(2)/dose weekly x 3 every 28 days in pediatric patients. The objective response rate across all dose levels and schedules was <10%. (c) 2008 Wiley-Liss, Inc.
Authors: M H Woo; M V Relling; D S Sonnichsen; G K Rivera; C B Pratt; C H Pui; W E Evans; A S Pappo Journal: Clin Cancer Res Date: 1999-03 Impact factor: 12.531
Authors: Robert J Hayashi; Susan Blaney; Jim Sullivan; Steve Weitman; Teresa Vietti; Mark L Bernstein Journal: J Pediatr Hematol Oncol Date: 2003-07 Impact factor: 1.289
Authors: C A Hurwitz; M V Relling; S D Weitman; Y Ravindranath; T J Vietti; D R Strother; A H Ragab; C B Pratt Journal: J Clin Oncol Date: 1993-12 Impact factor: 44.544
Authors: Eric S Schafer; Rachel E Rau; Stacey Berg; Xiaowei Liu; Charles G Minard; David D'Adamo; Rachael Scott; Larisa Reyderman; Gresel Martinez; Sandhya Devarajan; Joel M Reid; Elizabeth Fox; Brenda J Weigel; Susan M Blaney Journal: Pediatr Blood Cancer Date: 2018-05-02 Impact factor: 3.167
Authors: Holly L Pacenta; Wendy Allen-Rhoades; David Langenau; Peter J Houghton; Charles Keller; Christine M Heske; Michael D Deel; Corinne M Linardic; Jack F Shern; Elizabeth Stewart; Brian Turpin; Douglas J Harrison; Javed Khan; Leo Mascarenhas; Stephen X Skapek; William H Meyer; Douglas S Hawkins; Eleanor Y Chen; James F Amatruda; Pooja Hingorani; Theodore W Laetsch Journal: J Clin Med Date: 2021-04-01 Impact factor: 4.241