Phase I trial and pharmacokinetics of gemcitabine in children with advanced solid tumors

Joel M Reid, Wenchun Qu, Stephanie L. Safgren, Matthew M. Ames, Mark D. Krailo, Nita L. Seibel, John Kuttesch, John Holcenberg

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Abstract

Purpose: To determine the maximum tolerated dose, toxicity, and pharmacokinetics of gemcitabine in children with refractory solid tumors. Patients and Methods: Gemcitabine was given as a 30-minute infusion for 2 or 3 consecutive weeks every 4 weeks, to 42 patients aged 1 to 21 years. Doses of 1,000, 1,200 and 1,500 mg/m2 were administered for 3 weeks. Subsequently, gemcitabine was given for only 2 consecutive weeks at 1,500, 1,800, and 2,100 mg/m2. Plasma concentrations of gemcitabine and its metabolite, 2′2′-difluorodeoxyuridine, were measured in 28 patients. Results: Forty patients who received 132 courses of gemcitabine were assessable for toxicity. The maximum tolerated dose of gemcitabine given weekly for 3 weeks was 1,200 mg/m2. Dose-limiting toxicity was not seen in one-third of children treated at any doses given for 2 weeks. The major toxicity was myelosuppression in three of five patients at 1,500 mg/m2 for 3 weeks, and one of seven patients at 1,800 mg/m2 for 2 weeks. Other serious adverse events were somnolence, fever and hypotension, and rash in three patients. Gemcitabine plasma concentration-time data were fit to a one- (n = 5) or two-compartment (n = 23) open model. Mean gemcitabine clearance and half-life values were 2,140 mL/min/m2 and 13.7 minutes, respectively. One patient with pancreatic cancer had a partial response. Seven patients had stable disease for 2 to 17 months. Conclusion: Gemcitabine given by 30-minute infusion for 2 or 3 consecutive weeks every 4 weeks was tolerated well by children at doses of 2,100 mg/m2 and 1,200 mg/m2, respectively.

Original languageEnglish (US)
Pages (from-to)2445-2451
Number of pages7
JournalJournal of Clinical Oncology
Volume22
Issue number12
DOIs
StatePublished - 2004

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gemcitabine
Pharmacokinetics
Neoplasms
Maximum Tolerated Dose
Exanthema
Pancreatic Neoplasms
Hypotension

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

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Phase I trial and pharmacokinetics of gemcitabine in children with advanced solid tumors. / Reid, Joel M; Qu, Wenchun; Safgren, Stephanie L.; Ames, Matthew M.; Krailo, Mark D.; Seibel, Nita L.; Kuttesch, John; Holcenberg, John.

In: Journal of Clinical Oncology, Vol. 22, No. 12, 2004, p. 2445-2451.

Research output: Contribution to journalArticle

Reid, JM, Qu, W, Safgren, SL, Ames, MM, Krailo, MD, Seibel, NL, Kuttesch, J & Holcenberg, J 2004, 'Phase I trial and pharmacokinetics of gemcitabine in children with advanced solid tumors', Journal of Clinical Oncology, vol. 22, no. 12, pp. 2445-2451. https://doi.org/10.1200/JCO.2004.10.142
Reid, Joel M ; Qu, Wenchun ; Safgren, Stephanie L. ; Ames, Matthew M. ; Krailo, Mark D. ; Seibel, Nita L. ; Kuttesch, John ; Holcenberg, John. / Phase I trial and pharmacokinetics of gemcitabine in children with advanced solid tumors. In: Journal of Clinical Oncology. 2004 ; Vol. 22, No. 12. pp. 2445-2451.
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abstract = "Purpose: To determine the maximum tolerated dose, toxicity, and pharmacokinetics of gemcitabine in children with refractory solid tumors. Patients and Methods: Gemcitabine was given as a 30-minute infusion for 2 or 3 consecutive weeks every 4 weeks, to 42 patients aged 1 to 21 years. Doses of 1,000, 1,200 and 1,500 mg/m2 were administered for 3 weeks. Subsequently, gemcitabine was given for only 2 consecutive weeks at 1,500, 1,800, and 2,100 mg/m2. Plasma concentrations of gemcitabine and its metabolite, 2′2′-difluorodeoxyuridine, were measured in 28 patients. Results: Forty patients who received 132 courses of gemcitabine were assessable for toxicity. The maximum tolerated dose of gemcitabine given weekly for 3 weeks was 1,200 mg/m2. Dose-limiting toxicity was not seen in one-third of children treated at any doses given for 2 weeks. The major toxicity was myelosuppression in three of five patients at 1,500 mg/m2 for 3 weeks, and one of seven patients at 1,800 mg/m2 for 2 weeks. Other serious adverse events were somnolence, fever and hypotension, and rash in three patients. Gemcitabine plasma concentration-time data were fit to a one- (n = 5) or two-compartment (n = 23) open model. Mean gemcitabine clearance and half-life values were 2,140 mL/min/m2 and 13.7 minutes, respectively. One patient with pancreatic cancer had a partial response. Seven patients had stable disease for 2 to 17 months. Conclusion: Gemcitabine given by 30-minute infusion for 2 or 3 consecutive weeks every 4 weeks was tolerated well by children at doses of 2,100 mg/m2 and 1,200 mg/m2, respectively.",
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AU - Reid, Joel M

AU - Qu, Wenchun

AU - Safgren, Stephanie L.

AU - Ames, Matthew M.

AU - Krailo, Mark D.

AU - Seibel, Nita L.

AU - Kuttesch, John

AU - Holcenberg, John

PY - 2004

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N2 - Purpose: To determine the maximum tolerated dose, toxicity, and pharmacokinetics of gemcitabine in children with refractory solid tumors. Patients and Methods: Gemcitabine was given as a 30-minute infusion for 2 or 3 consecutive weeks every 4 weeks, to 42 patients aged 1 to 21 years. Doses of 1,000, 1,200 and 1,500 mg/m2 were administered for 3 weeks. Subsequently, gemcitabine was given for only 2 consecutive weeks at 1,500, 1,800, and 2,100 mg/m2. Plasma concentrations of gemcitabine and its metabolite, 2′2′-difluorodeoxyuridine, were measured in 28 patients. Results: Forty patients who received 132 courses of gemcitabine were assessable for toxicity. The maximum tolerated dose of gemcitabine given weekly for 3 weeks was 1,200 mg/m2. Dose-limiting toxicity was not seen in one-third of children treated at any doses given for 2 weeks. The major toxicity was myelosuppression in three of five patients at 1,500 mg/m2 for 3 weeks, and one of seven patients at 1,800 mg/m2 for 2 weeks. Other serious adverse events were somnolence, fever and hypotension, and rash in three patients. Gemcitabine plasma concentration-time data were fit to a one- (n = 5) or two-compartment (n = 23) open model. Mean gemcitabine clearance and half-life values were 2,140 mL/min/m2 and 13.7 minutes, respectively. One patient with pancreatic cancer had a partial response. Seven patients had stable disease for 2 to 17 months. Conclusion: Gemcitabine given by 30-minute infusion for 2 or 3 consecutive weeks every 4 weeks was tolerated well by children at doses of 2,100 mg/m2 and 1,200 mg/m2, respectively.

AB - Purpose: To determine the maximum tolerated dose, toxicity, and pharmacokinetics of gemcitabine in children with refractory solid tumors. Patients and Methods: Gemcitabine was given as a 30-minute infusion for 2 or 3 consecutive weeks every 4 weeks, to 42 patients aged 1 to 21 years. Doses of 1,000, 1,200 and 1,500 mg/m2 were administered for 3 weeks. Subsequently, gemcitabine was given for only 2 consecutive weeks at 1,500, 1,800, and 2,100 mg/m2. Plasma concentrations of gemcitabine and its metabolite, 2′2′-difluorodeoxyuridine, were measured in 28 patients. Results: Forty patients who received 132 courses of gemcitabine were assessable for toxicity. The maximum tolerated dose of gemcitabine given weekly for 3 weeks was 1,200 mg/m2. Dose-limiting toxicity was not seen in one-third of children treated at any doses given for 2 weeks. The major toxicity was myelosuppression in three of five patients at 1,500 mg/m2 for 3 weeks, and one of seven patients at 1,800 mg/m2 for 2 weeks. Other serious adverse events were somnolence, fever and hypotension, and rash in three patients. Gemcitabine plasma concentration-time data were fit to a one- (n = 5) or two-compartment (n = 23) open model. Mean gemcitabine clearance and half-life values were 2,140 mL/min/m2 and 13.7 minutes, respectively. One patient with pancreatic cancer had a partial response. Seven patients had stable disease for 2 to 17 months. Conclusion: Gemcitabine given by 30-minute infusion for 2 or 3 consecutive weeks every 4 weeks was tolerated well by children at doses of 2,100 mg/m2 and 1,200 mg/m2, respectively.

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