Studies from University of Texas further understanding of pharmacokinetics
2008 JAN 14 -- "The purpose of this trial was to define the maximum tolerated duration (MTD), dose-limiting toxicity (DLT), regimen-related toxicities (RRT), and pharmacokinetics of gemcitabinc infused at a fixed dose rate (FDR) of 10 mg/m(2)/min, combined with docetaxel/melphalan/carboplatin, using autologous stem cell transplantation (ASCT). The duration of gemcitabine infusion was incrementally escalated as a single treatment on day -6 or as 4 daily infusions on days -5 to -2," investigators in the United States report. "Gemcitabine was followed by docetaxel (300 or 350 mg/m(2)) on day -5, and then melphalan (50 mg/m(2)/day) and carboplatin (333 mg/m(2)/day) on days -4 to -2. Fifty-two patients with refractory tumors were accrued with a median age of 40 (range: 6-66), a median of 3 (1-6) prior chemotherapy regimens, and 3 (1-7) organs involved. The gemcitabine MTD was defined at 20 hours (total dose 12,000 mg/m(2)) on both schedules. The DLT was enteritis. Three patients died from aspiration, catheter-related sepsis, and enteritis, respectively. The tumor response rate was 91%, with 50% complete responses. At current 2-year median follow-up, the event-free and overall survival (EFS, OS) rates are 54% (median 26 months) and 79% (median not reached), respectively. Gemcitabine area under the curve (AUC), but not clearance, increased linearly with infusion duration, and correlated with grade 3 RRT. Docetaxel showed a linear increase of its AUC and similar clearance compared with prior reports at lower doses," wrote Y. Nieto and colleagues, University of Texas. The researchers concluded: "ASCT-supported infusions of gemcitabine at FDR could be prolonged up to 20 hours. The resulting gemcitabine/docetaxel/melphalan/carboplatin combination was highly active in refractory cancers and should be further tested in disease-specific trials." Nieto and colleagues published their study in Biology of Blood and Marrow Transplantation (Phase I and pharmacokinetic study of gemcitabine administered at fixed-dose rate, combined with Docetaxel/Mephalan/Carboplatin, with autologous hematopoietic progenitor-cell support, in patients with advanced refractory tumors. Biology of Blood and Marrow Transplantation, 2007;13(11):1324-1337). For additional information, contact Y. Nieto, University of Texas, MD Anderson Cancer Center, Dept. of Stem Cell Transplantation & Cellular Therapy, Unit 423, 1515 Holcombe Blvd., Houston, TX 77030, USA. The publisher of the journal Biology of Blood and Marrow Transplantation can be contacted at: Elsevier Science Inc., 360 Park Avenue South, New York, NY 10010-1710, USA. Keywords: United States, Houston, Antimetabolite, Antineoplastic, Antiviral, Carboplatin, Cell Transplantation, Chemotherapy, Clinical Trial Research, Docetaxel, Drug Therapy, Drugs, Gemcitabine, Hematology, Hematopoietic, Immunosuppressant, Melphalan, Pharmaceuticals, Pharmacokinetics, Progenitor Cell, Radiation-Sensitizing Agent, Stem Cell Research, Therapies, Treatment, University of Texas. This article was prepared by Stem Cell Week editors from staff and other reports. Copyright 2008, Stem Cell Week via NewsRx.com.
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