High-dose topotecan with granulocyte-colony stimulating factor in fluoropyrimidine-refractory colorectal cancer: a phase II and pharmacodynamic study

Annals of Oncology : Official Journal of the European Society for Medical Oncology
E K RowinskyL B Grochow

Abstract

The premise for this study was that topotecan (TPT) resistance in preclinical studies is associated with low level expression of the p-glycoprotein (Pgp) multi-drug transporter conferred by the multi-drug resistant (MDR) phenotype, which might be overcome in clinical practice by administering moderately (2.3-fold) higher doses of TPT that have shown to be feasible with granulocyte colony-stimulating factor (G-CSF) support. This phase II study evaluated the anti-tumor activity of TPT administered at its highest possible solid tumor dose with G-SCF in patients with fluoropyrimidine-refractory advanced colorectal carcinoma. The study also sought to identify pharmacodynamic (PD) determinants of both activity and toxicity. TPT was administered as a 30-minute infusion daily for five days every three weeks at a dose of 3.5 mg/m2/day to patients with advance colorectal carcinoma who developed progressive disease either during treatment with fluoropyrimidine-based chemotherapy for advanced disease or within six months after receiving fluoropyrimidine-based adjuvant chemotherapy. This dose of TPT was previously determined to be the maximal tolerated dose (MTD) with G-CSF support in a phase I study involving solid tumor patients with simi...Continue Reading

Citations

Mar 7, 2001·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·U VanhoeferY M Rustum
Feb 9, 2008·Pharmacology·Howard R Mellor, Richard Callaghan
Mar 23, 2001·Anti-cancer Drugs·D F KehrerA Sparreboom
Aug 18, 2020·Cardiovascular and Interventional Radiology·Andrew S MikhailBradford J Wood
Jan 30, 2010·Molecular Pharmaceutics·Vincent J Venditto, Eric E Simanek

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