PMID: 7520844Jan 1, 1994Paper

Camptothecin analogues: studies from the Johns Hopkins Oncology Center

Cancer Chemotherapy and Pharmacology
W J SlichenmyerR C Donehower

Abstract

The camptothecin analogues topotecan and irinotecan (CPT-11) are active anticancer drugs. This article reviews the accumulated results of clinical and laboratory studies performed with these agents at The Johns Hopkins Oncology Center. In a phase I clinical and pharmacology trial of topotecan given as a 30-min infusion daily for 5 days every 3 weeks, profound neutropenia precluded dose escalation above 1.5-2.0 mg/m2 per day, the maximum tolerated dose (MTD). The daily x5 schedule has been developed further with dose escalation using granulocyte-colony-stimulating factor support in patients who have kidney or liver dysfunction and given in combination with cisplatin. In addition, a phase I trial of topotecan given as a 5-day continuous intravenous infusion to patients with refractory leukemia has had promising antileukemic responses. A separate series of in vitro studies indicates that a modest degree of resistance to the cytotoxicity of topotecan can be mediated by P-glycoprotein. A phase I and pharmacology study of irinotecan given as a 90-min infusion every 3 weeks has defined an MTD of 240 mg/m2, with dose escalation being limited by several toxicities. These included an acute treatment-related syndrome of flushing, warmth, ...Continue Reading

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Citations

Sep 28, 1998·Cancer Chemotherapy and Pharmacology·L Iyer, M J Ratain
Jul 10, 2004·Supportive Care in Cancer : Official Journal of the Multinational Association of Supportive Care in Cancer·K A Al-Anazi, S Jacobs
May 12, 2004·Neuro-oncology·David A ReardonHenry S Friedman
Jun 16, 2010·Pharmacology & Therapeutics·Leopold ArkoJohn K Park
Sep 22, 2009·Critical Reviews in Oncology/hematology·Domenica LorussoGiovanni Scambia
Aug 29, 2007·Clinics in Liver Disease·Edmundo A Rodriguez-Frias, William M Lee
Jul 12, 2005·Expert Opinion on Investigational Drugs·Michele ReniAlba A Brandes
Sep 30, 2006·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Peter J O'Dwyer, Robert B Catalano
Feb 14, 2006·Seminars in Oncology·Justin FloydMichael C Perry
May 13, 2008·Expert Review of Anticancer Therapy·Lynn Feun, Niramol Savaraj
Apr 17, 2003·The Oncologist·Sarah McKenna, Martin Eatock
Jul 29, 2020·Journal of Liposome Research·Shivani SarafSanjay K Jain
Dec 15, 2010·Anais Brasileiros De Dermatologia·Paulo Ricardo CriadoJose Antonio Sanches Júnior
May 20, 1999·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·H S FriedmanL L Miller

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