Developing Drugs to Decrease the Toxicity of Chemotherapy

Abstract

Article Tools SPECIAL DEPARTMENTS Article Tools OPTIONS & TOOLS Export Citation Track Citation Add To Favorites Rights & Permissions COMPANION ARTICLES No companion articles ARTICLE CITATION DOI: 10.1200/JCO.2001.19.14.3439 Journal of Clinical Oncology - published online before print September 21, 2016 PMID: 11454894 Developing Drugs to Decrease the Toxicity of Chemotherapy Grant WilliamsxGrant WilliamsSearch for articles by this author , Patricia CortazarxPatricia CortazarSearch for articles by this author , Richard PazdurxRichard PazdurSearch for articles by this author Gerald BatistxGerald BatistSearch for articles by this author , Lauri WellesxLauri WellesSearch for articles by this author Show More United States Food and Drug Administration, Rockville, MDJewish General Hospital, McGill University, Montreal, CanadaElan Pharmaceuticals, Princeton, NJ https://doi.org/10.1200/JCO.2001.19.14.3439 First Page Full Text PDF Figures and Tables © 2001 by American Society of Clinical OncologyjcoJ Clin OncolJournal of Clinical OncologyJCO0732-183X1527-7755American Society of Clinical OncologyResponse15072001In Reply:We would like to respond to the letter by Drs Williams, Cortazar, and Pazdur with respect to the relative complexities of clinical trial design and analysis and the need for randomized clinical trials with sufficient power to detect true efficacy differences, should they exist. They note that our published trial1 met all safety and efficacy end points, but that a second, smaller, single-agent study, which has not yet been published, was inadequately powered and couldn't exclude the possibility that the cardiac sparing qualities of the TLC D-99 liposomal formulation (Myocet) might reduce doxorubicin's antitumor efficacy. First, as we are both among the authors of an upcoming report of that study, we would like to assure Williams et al that the report of that study has been submitted for publication.The manuscript provides detailed discussion of specific points and interpretations of the data referred to in the Williams et al letter. However, we do agree that the study had several design flaws among which was, as Williams et al correctly point out, the fact that it was underpowered due, in part, to erroneous assumptions regarding anticipated response rates in both the control and the experimental arms. With the benefit of hindsight, if we were to repeat the trial (which, unfortunately, is not possible, because single-agent doxorubicin is no longer standard of care for first-line therapy of metastatic breast cancer), we would alter the design and statistical approach. Additional clinical trials with TLC D-99 in combination with various other agents are underway. Preliminary results of one such trial will be presented at the 2001 Annual Meeting of the American Society of Clinical Oncology, and a larger, randomized phase III trial of TLC-99 in a combination regimen is anticipated. The views expressed herein do not necessarily represent the views or findings of the United States Food and Drug Administration or the United States Government. REFERENCE1. Batist G, Ramakrishnan G, Sekhar Rao C, et al: Reduced cardiotoxicity and preserved antitumor efficacy of liposome-encapsulated doxorubicin and cyclophosphamide compared with conventional doxorubicin and cyclophosphamide in a randomized multicenter trial of metastatic breast cancer. J Clin Oncol 19:: 1444,2001-1454, Link, Google Scholar