A phase 1 and pharmacokinetic clinical trial of paclitaxel for the treatment of refractory leukemia in children: A Children's Oncology Group Study

Terzah M. Horton, Matthew M. Arnes, Joel M Reid, Mark D. Krailo, Thomas Pendergrass, Revonda Mosher, Gregory H. Reaman, Nita L. Seibel

Research output: Contribution to journalArticle

12 Citations (Scopus)

Abstract

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/m2 every 21 days in schedule A and 105 to 200 mg/m2 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/m2 every 21 days. The DLTs in schedule B were coagulopathy, hyperkalemia, hyperbilirubinemia, elevated SGOT (n = 1, 125 mg/m2), peripheral neuropathy (n = 1, 200 mg/m2), and typhlitis (n = 1, 200 mg/m 2) with an MTD of 182 mg/m2 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/m2. Conclusions. Paclitaxel was tolerated at 430 mg/m2 every 21 days and at 182 mg/m2/dose weekly x 3 every 28 days in pediatric patients. The objective response rate across all dose levels and schedules was <10%.

Original languageEnglish (US)
Pages (from-to)788-792
Number of pages5
JournalPediatric Blood and Cancer
Volume50
Issue number4
DOIs
StatePublished - Apr 2008

Fingerprint

Clinical Trials, Phase I
Paclitaxel
Appointments and Schedules
Leukemia
Pharmacokinetics
Maximum Tolerated Dose
Hyperbilirubinemia
Typhlitis
Therapeutics
Hyperkalemia
Peripheral Nervous System Diseases
Aspartate Aminotransferases
Acute Myeloid Leukemia
Half-Life
Pediatrics
Hypertension
Neoplasms

Keywords

  • ALL
  • AML
  • Lymphoblastic
  • Myelogenous
  • Pediatric
  • Taxol

ASJC Scopus subject areas

  • Cancer Research
  • Pediatrics, Perinatology, and Child Health
  • Hematology

Cite this

A phase 1 and pharmacokinetic clinical trial of paclitaxel for the treatment of refractory leukemia in children : A Children's Oncology Group Study. / Horton, Terzah M.; Arnes, Matthew M.; Reid, Joel M; Krailo, Mark D.; Pendergrass, Thomas; Mosher, Revonda; Reaman, Gregory H.; Seibel, Nita L.

In: Pediatric Blood and Cancer, Vol. 50, No. 4, 04.2008, p. 788-792.

Research output: Contribution to journalArticle

Horton, Terzah M. ; Arnes, Matthew M. ; Reid, Joel M ; Krailo, Mark D. ; Pendergrass, Thomas ; Mosher, Revonda ; Reaman, Gregory H. ; Seibel, Nita L. / A phase 1 and pharmacokinetic clinical trial of paclitaxel for the treatment of refractory leukemia in children : A Children's Oncology Group Study. In: Pediatric Blood and Cancer. 2008 ; Vol. 50, No. 4. pp. 788-792.
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T1 - A phase 1 and pharmacokinetic clinical trial of paclitaxel for the treatment of refractory leukemia in children

T2 - A Children's Oncology Group Study

AU - Horton, Terzah M.

AU - Arnes, Matthew M.

AU - Reid, Joel M

AU - Krailo, Mark D.

AU - Pendergrass, Thomas

AU - Mosher, Revonda

AU - Reaman, Gregory H.

AU - Seibel, Nita L.

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AB - 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/m2 every 21 days in schedule A and 105 to 200 mg/m2 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/m2 every 21 days. The DLTs in schedule B were coagulopathy, hyperkalemia, hyperbilirubinemia, elevated SGOT (n = 1, 125 mg/m2), peripheral neuropathy (n = 1, 200 mg/m2), and typhlitis (n = 1, 200 mg/m 2) with an MTD of 182 mg/m2 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/m2. Conclusions. Paclitaxel was tolerated at 430 mg/m2 every 21 days and at 182 mg/m2/dose weekly x 3 every 28 days in pediatric patients. The objective response rate across all dose levels and schedules was <10%.

KW - ALL

KW - AML

KW - Lymphoblastic

KW - Myelogenous

KW - Pediatric

KW - Taxol

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