Relationship between topotecan systemic exposure and tumor response in human neuroblastoma xenografts

Journal of the National Cancer Institute
W C ZamboniP J Houghton

Abstract

Topotecan is a topoisomerase I inhibitor with activity against xenografts of childhood solid tumors and established clinical activity against neuroblastoma and rhabdomyosarcoma. We have studied the relationship between systemic exposure to and the antitumor activity of topotecan lactone (the active form of the drug) in the xenograft models. Furthermore, we determined whether the responses seen in these models occur at systemic exposure levels that are tolerable in children. Neuroblastoma xenografts derived from the tumors of six different patients were established subcutaneously in immune-deprived mice. Topotecan was administered by intravenous bolus injection 5 days a week for 2 consecutive weeks, repeated every 21 days for three cycles. The minimum daily doses that induced complete responses (CRs) and partial responses (PRs) were determined. Topotecan lactone pharmacokinetic studies were performed in both tumor-bearing and nontumor-bearing mice. The minimum doses associated with CRs and PRs in four of the six neuroblastoma xenografts were 0.61 and 0.36 mg/kg body weight, respectively. The topotecan lactone single-day systemic exposures associated with these doses were 88 and 52 ng x hr/mL, respectively. There was an approxima...Continue Reading

References

Mar 1, 1979·Computer Programs in Biomedicine·D Z D'Argenio, A Schumitzky
Jan 1, 1989·Cancer Chemotherapy and Pharmacology·P J HoughtonG B Grindey
Jun 1, 1989·Clinical Pharmacokinetics·W E Evans, M V Relling
Nov 1, 1982·Drug Intelligence & Clinical Pharmacy·W E EvansW R Crom
Nov 1, 1994·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·J H RodmanV M Santana
Sep 1, 1994·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·C F StewartC B Pratt
Mar 1, 1994·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·C B PrattJ T Sandlund
May 1, 1996·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·W L FurmanC F Stewart

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Citations

Dec 18, 2001·International Journal of Cancer. Journal International Du Cancer·Y ChenH D Suit
Apr 6, 2001·International Journal of Cancer. Journal International Du Cancer·C Beltinger, K M Debatin
Aug 31, 2013·European Journal of Clinical Pharmacology·Huali WuWilliam C Zamboni
Jul 8, 2005·Cancer Chemotherapy and Pharmacology·Carlos Rodriguez-GalindoVictor M Santana
Jul 28, 2005·Cancer Chemotherapy and Pharmacology·P Kellie TurnerClinton F Stewart
Dec 20, 2008·Cancer Chemotherapy and Pharmacology·Inge R H M KoningsWalter J Loos
May 5, 2007·Journal of Cancer Research and Clinical Oncology·Thorsten SimonBarbara Hero
Feb 5, 2008·Investigational New Drugs·William C ZamboniJulie L Eiseman
May 4, 2004·European Journal of Cancer : Official Journal for European Organization for Research and Treatment of Cancer (EORTC) [and] European Association for Cancer Research (EACR)·J K Peterson, P J Houghton
Sep 28, 1998·Biochimica Et Biophysica Acta·J ThompsonP J Houghton
Aug 21, 2003·Cancer Treatment Reviews·E J Estlin, G J Veal
Jun 8, 2001·International Journal of Radiation Oncology, Biology, Physics·P ChastagnerA Taghian
Dec 23, 1998·Journal of the National Cancer Institute·Y OhnishiY Ueyama
Aug 7, 2003·Journal of Pediatric Hematology/oncology·Kim KramerNai-Kong V Cheung
Oct 4, 2005·The Cancer Journal·Peter C Adamson, Susan M Blaney
Feb 7, 2007·Journal of Pediatric Hematology/oncology·Thorsten SimonBarbara Hero
May 25, 2013·Journal of Pediatric Hematology/oncology·Daniel A MorgensternMeredith S Irwin
Feb 5, 2009·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·William C ZamboniRamesh K Ramanathan
Feb 25, 2010·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Radhika IyerGarrett M Brodeur
Oct 20, 2011·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Julie R ParkKatherine K Matthay
Dec 26, 2001·European Journal of Cancer : Official Journal for European Organization for Research and Treatment of Cancer (EORTC) [and] European Association for Cancer Research (EACR)·A SparreboomJ Verweij
May 9, 2014·Cancer Chemotherapy and Pharmacology·Eleftheria TsakalozouMarkos Leggas
Oct 24, 2008·Xenobiotica; the Fate of Foreign Compounds in Biological Systems·P Ahlawat, N R Srinivas
Aug 6, 2004·Journal of Pharmaceutical Sciences·Markos LeggasClinton F Stewart
May 24, 2011·Biometrical Journal. Biometrische Zeitschrift·Maiying Kong, Jun Yan
Jul 12, 2011·Pediatric Blood & Cancer·Peter J HoughtonMalcolm A Smith
Sep 1, 2015·Clinical Sarcoma Research·Lars M Wagner
Aug 14, 2009·Clinical Pharmacology and Therapeutics·W C ZamboniR K Ramanathan
Jun 19, 2010·European Journal of Cancer : Official Journal for European Organization for Research and Treatment of Cancer (EORTC) [and] European Association for Cancer Research (EACR)·Hervé RubieGilles Vassal
Jul 19, 2016·Colloids and Surfaces. B, Biointerfaces·Paula TaichPaula Schaiquevich
Dec 18, 2009·Pediatric Blood & Cancer·Hernan CarolRichard B Lock
Sep 1, 2016·The Journal of Pharmacy and Pharmacology·Paula TaichPaula Schaiquevich
Aug 18, 2004·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Clinton F StewartAmar Gajjar
Jun 18, 2005·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Victor M SantanaClinton F Stewart
Oct 16, 2004·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Cynthia S KretschmarRobert Castleberry
Oct 27, 2006·Pediatric Blood & Cancer·Peter J HoughtonMalcolm A Smith
Dec 2, 2014·Pediatric Clinics of North America·Malcolm A Smith, Gregory H Reaman

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