{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,4]],"date-time":"2026-10-04T14:16:01Z","timestamp":1791123361907,"version":"4.1.0"},"reference-count":13,"publisher":"American Society of Clinical Oncology (ASCO)","issue":"12","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JCO"],"published-print":{"date-parts":[[2004,6,15]]},"abstract":"<jats:sec><jats:title>Purpose<\/jats:title><jats:p> To determine the maximum tolerated dose, toxicity, and pharmacokinetics of gemcitabine in children with refractory solid tumors. <\/jats:p><\/jats:sec><jats:sec><jats:title>Patients and Methods<\/jats:title><jats:p> 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\/m<jats:sup>2<\/jats:sup> were administered for 3 weeks. Subsequently, gemcitabine was given for only 2 consecutive weeks at 1,500, 1,800, and 2,100 mg\/m<jats:sup>2<\/jats:sup>. Plasma concentrations of gemcitabine and its metabolite, 2\u20322\u2032-difluorodeoxyuridine, were measured in 28 patients. <\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p> 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\/m<jats:sup>2<\/jats:sup>. 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\/m<jats:sup>2<\/jats:sup> for 3 weeks, and one of seven patients at 1,800 mg\/m<jats:sup>2<\/jats:sup> for 2 weeks. Other serious adverse events were somnolence, fever and hypotension, and rash in three patients. Gemcitabine plasma concentration\u2013time 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\/m<jats:sup>2<\/jats:sup> and 13.7 minutes, respectively. One patient with pancreatic cancer had a partial response. Seven patients had stable disease for 2 to 17 months. <\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p> 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\/m<jats:sup>2<\/jats:sup> and 1,200 mg\/m<jats:sup>2<\/jats:sup>, respectively. <\/jats:p><\/jats:sec>","DOI":"10.1200\/jco.2004.10.142","type":"journal-article","created":{"date-parts":[[2004,6,15]],"date-time":"2004-06-15T18:03:07Z","timestamp":1087322587000},"page":"2445-2451","source":"Crossref","is-referenced-by-count":97,"title":["Phase I Trial and Pharmacokinetics of Gemcitabine in Children With Advanced Solid Tumors"],"prefix":"10.1200","volume":"22","author":[{"given":"Joel M.","family":"Reid","sequence":"first","affiliation":[{"name":"From the Mayo Clinic, Rochester, MN; Children's Hospital Medical Center, Seattle, WA; Children's Oncology Group Operations Center, Arcadia; University of Southern California Keck School of Medicine, Los Angeles, CA; Children's National Medical Center, Washington, DC; and Vanderbilt Children's Hospital, Nashville, TN"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenchun","family":"Qu","sequence":"additional","affiliation":[{"name":"From the Mayo Clinic, Rochester, MN; Children's Hospital Medical Center, Seattle, WA; Children's Oncology Group Operations Center, Arcadia; University of Southern California Keck School of Medicine, Los Angeles, CA; Children's National Medical Center, Washington, DC; and Vanderbilt Children's Hospital, Nashville, TN"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephanie L.","family":"Safgren","sequence":"additional","affiliation":[{"name":"From the Mayo Clinic, Rochester, MN; Children's Hospital Medical Center, Seattle, WA; Children's Oncology Group Operations Center, Arcadia; University of Southern California Keck School of Medicine, Los Angeles, CA; Children's National Medical Center, Washington, DC; and Vanderbilt Children's Hospital, Nashville, TN"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthew M.","family":"Ames","sequence":"additional","affiliation":[{"name":"From the Mayo Clinic, Rochester, MN; Children's Hospital Medical Center, Seattle, WA; Children's Oncology Group Operations Center, Arcadia; University of Southern California Keck School of Medicine, Los Angeles, CA; Children's National Medical Center, Washington, DC; and Vanderbilt Children's Hospital, Nashville, TN"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mark D.","family":"Krailo","sequence":"additional","affiliation":[{"name":"From the Mayo Clinic, Rochester, MN; Children's Hospital Medical Center, Seattle, WA; Children's Oncology Group Operations Center, Arcadia; University of Southern California Keck School of Medicine, Los Angeles, CA; Children's National Medical Center, Washington, DC; and Vanderbilt Children's Hospital, Nashville, TN"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nita L.","family":"Seibel","sequence":"additional","affiliation":[{"name":"From the Mayo Clinic, Rochester, MN; Children's Hospital Medical Center, Seattle, WA; Children's Oncology Group Operations Center, Arcadia; University of Southern California Keck School of Medicine, Los Angeles, CA; Children's National Medical Center, Washington, DC; and Vanderbilt Children's Hospital, Nashville, TN"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John","family":"Kuttesch","sequence":"additional","affiliation":[{"name":"From the Mayo Clinic, Rochester, MN; Children's Hospital Medical Center, Seattle, WA; Children's Oncology Group Operations Center, Arcadia; University of Southern California Keck School of Medicine, Los Angeles, CA; Children's National Medical Center, Washington, DC; and Vanderbilt Children's Hospital, Nashville, TN"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John","family":"Holcenberg","sequence":"additional","affiliation":[{"name":"From the Mayo Clinic, Rochester, MN; Children's Hospital Medical Center, Seattle, WA; Children's Oncology Group Operations Center, Arcadia; University of Southern California Keck School of Medicine, Los Angeles, CA; Children's National Medical Center, Washington, DC; and Vanderbilt Children's Hospital, Nashville, TN"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"233","reference":[{"key":"R1","unstructured":"Heinemann V, Hertel L, Grindey G, et al: Comparison of the cellular pharmacokinetics and toxicity of 2\u2032,2\u2032-difluorodeoxycytidine. 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