Phase I study of flavopiridol with oxaliplatin and fluorouracil/leucovorin in advanced solid tumors.

Clinical Cancer Research : an Official Journal of the American Association for Cancer Research
Dana E RathkopfGary K Schwartz

Abstract

Flavopiridol, a cyclin-dependent kinase inhibitor, has promising clinical activity when combined with chemotherapy. Preclinical data indicate that flavopiridol enhances oxaliplatin- and fluorouracil (5FU)-induced apoptosis in a sequence-dependent manner. We conducted a phase I trial of flavopiridol + FOLFOX (folinic acid, 5FU, and oxaliplatin) for advanced solid tumors. Flavopiridol was administered every 2 weeks with oxaliplatin before 5FU, based on sequence-dependent growth inhibition. Flavopiridol pharmacokinetics and p53 status were evaluated. Forty-eight patients were treated on study. With dose escalation of oxaliplatin (85 mg/m(2)) and 5FU (2,400 mg/m(2)), dose-limiting toxicities included hyponatremia, thrombocytopenia, and neutropenia. 5FU was subsequently reduced to allow for dose escalation of flavopiridol. Dose-limiting toxicities with escalation of flavopiridol were nausea, vomiting, and neutropenia. The maximum tolerated dose was 70 mg/m(2) flavopiridol, 85 mg/m(2) oxaliplatin, and 1,800 mg/m(2) 5FU continuous infusion over 48 hours. Clinical activity was noted in platinum-refractory germ cell tumors: 3 of 9 (33%) evaluable patients showed a partial response on imaging and 7 of 10 (70%) had a decline in serum tumo...Continue Reading

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Citations

Mar 1, 2012·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Jason J LukeGary K Schwartz
Aug 5, 2011·Drugs·Jaclyn YoongTrevor Leong
Feb 13, 2014·British Journal of Cancer·A H BeesleyU R Kees
Aug 31, 2011·Journal of Cancer Research and Clinical Oncology·Jonas Cicenas, Mindaugas Valius
Mar 29, 2014·Expert Review of Gastroenterology & Hepatology·Salah-Eddin Al-Batran, Dominique Werner
Oct 29, 2014·Cancers·Jonas CicenasMindaugas Valius
May 30, 2015·Expert Opinion on Emerging Drugs·Bruno VincenziGiuseppe Tonini
Nov 7, 2012·Expert Opinion on Emerging Drugs·Soley Bayraktar, Caio M Rocha Lima
Aug 12, 2014·Expert Opinion on Investigational Drugs·Carmen CriscitielloGiuseppe Curigliano
Oct 10, 2015·Current Oncology Reports·Christian Daniel FankhauserPeter Karl Bode
Apr 1, 2016·Nature Reviews. Clinical Oncology·Ben O'LearyNicholas C Turner
Mar 10, 2015·The American Journal of Pathology·Sameh MikhailMichael J Pishvaian
Jun 11, 2016·Expert Opinion on Investigational Drugs·Christoph OingCarsten Bokemeyer
Apr 26, 2017·The Journal of Organic Chemistry·Dávid PajtásTamás Patonay
Apr 11, 2012·Laboratory Investigation; a Journal of Technical Methods and Pathology·Yulan ChengYuriko Mori
Oct 21, 2018·International Journal of Molecular Sciences·Balbina García-ReyesJohannes Lemke
Aug 7, 2019·Therapeutic Advances in Medical Oncology·Zhimin TongDipen M Maru
Mar 14, 2020·Expert Review of Anticancer Therapy·Paolo ChieffiFrancesco Esposito

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