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A Phase 1 and pharmacokinetic clinical trial of paclitaxel for the treatment of refractory leukemia in children: A Children's Oncology Group study
Author(s) -
Horton Terzah M.,
Ames Matthew M.,
Reid Joel M.,
Krailo Mark D.,
Pendergrass Thomas,
Mosher Revonda,
Reaman Gregory H.,
Seibel Nita L.
Publication year - 2008
Publication title -
pediatric blood and cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.116
H-Index - 105
eISSN - 1545-5017
pISSN - 1545-5009
DOI - 10.1002/pbc.21310
Subject(s) - medicine , pharmacokinetics , refractory (planetary science) , paclitaxel , gastroenterology , myeloid leukemia , leukemia , chemotherapy , astrobiology , physics
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 × 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 × 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 × 3 every 28 days in pediatric patients. The objective response rate across all dose levels and schedules was <10%. Pediatr Blood Cancer 2008;50:788–792. © 2007 Wiley‐Liss, Inc.