Liposomal Doxorubicin and the Accelerated Approval Process TO THE EDITOR: I would like to comment on Drs Joseph DiMasi and Henry Grabowski’s review, 1 published in the January 10, 2007, issue of the Journal of Clinical Oncology. The authors failed to list Doxil (generically known as doxorubi- cin; Ortho Biotech Products, Bridgewater, NJ) in Table 1, which presented the new oncology drugs approved in the United States from 1990 to 2005. While this omission may seem trivial, it is not if one considers that Doxil was the first accelerated oncology drug approval and helped usher in an era of rapid drug approvals based on the surrogate marker, tumor response. Having defended Doxil before the Oncology Drug Advisory Committee leading to its approval, I have become keenly aware of the advantages and disadvantages of the accelerated approval process. As we now know, tumor shrinkage is not always a surrogate for improved survival or quality of life. Another major point overlooked in this review was that many industry sponsors of oncology drugs approved by this process have failed to submit confirmatory, postapproval trials as required under the accelerated approval process. Coupled with the high cost these drugs put on the health care system, many are left to think that commercial companies have abused the opportunity pro- vided by the accelerated approval process. However, as oncologists, we all want promising therapies available for our patients as early as possible. Perhaps we should consider keeping the accelerated approval process available while restricting the reimbursement to the company until randomized, controlled trials showing an effect of survival or quality of life have been conducted. Alternatively, US oncologists must fully support phase III, randomized clinical trials comparing experi- mental therapies to best supportive care when there are no approved therapies for the indicated patient population. George Tidmarsh Institute for Cancer Drug Development, Palo Alto, CA AUTHOR’S DISCLOSURES OF POTENTIAL CONFLICTS OF INTEREST The author indicated no potential conflicts of interest. REFERENCE 1. DiMasi JA, Grabowski HG: Economics of new oncology drug development. J Clin Oncol 25:209-216, 2007 DOI: 10.1200/JCO.2007.11.0924 ■ ■ ■ IN REPLY: Dr Tidmarsh is correct that Table 1 in our article 1 does not contain Doxil (Ortho Biotech Products, Bridgewater, NJ), but this is not an error. The table is a list of therapeutic new chemical entities and corresponding therapeutically significant new biologics first ap- proved by the US Food and Drug Administration from 1990 to 2005 for oncology indications. Doxil is a new (liposomal) formulation, not a new chemical entity. Doxorubicin, the active ingredient in Doxil, was first approved by the US Food and Drug Administration in 1974 under the trade name Adriamycin (Pfizer Inc, New York, NY). Thus, neither Adriamycin nor Doxil met the criteria for inclusion in the table. Undoubtedly, the approval of Doxil represented an important milestone in the history of the accelerated approval process for oncol- ogy drugs, and some new formulations are important clinical ad- vances over existing formulations of the same drugs. However, our analyses (and the data that we had available for those analyses) were about first approvals of new active ingredients, not every product variant developed during a drug’s life cycle. Joseph A. DiMasi Tufts Center for the Study of Drug Development, Tufts University, Medford, MA Henry G. Grabowski Department of Economics, Duke University, Durham, NC AUTHORS’ DISCLOSURES OF POTENTIAL CONFLICTS OF INTEREST The authors indicated no potential conflicts of interest. REFERENCE 1. DiMasi JA, Grabowski HG: Economics of new oncology drug development. J Clin Oncol 25:209-216, 2007 DOI: 10.1200/JCO.2007.11.6020 ■ ■ ■ Impact of Toxicity Assumptions on Socioeconomic Analysis of Breast Cancer Chemotherapy TO THE EDITOR: I am pleased to see the analysis of socioeco- nomic status and outcomes in the recent study by Griggs et al. 1 How- ever, they assume that community physicians’ biases may be the major reason for lower first chemotherapy dosing for patients of lower so- cioeconomic status. The authors state that first chemotherapy dose differences may be due to “providers’ anticipation of a different re- sponse to the same adverse effects rather than a different adverse effect profile.” However, there is a higher toxicity from adjuvant therapy for patients from lower socioeconomic strata. Hassett et al 2 reported JOURNAL OF CLINICAL ONCOLOGY C O R R E S P O N D E N C E VOLUME 25  NUMBER 16  JUNE 1 2007 2331 Journal of Clinical Oncology, Vol 25, No 16 (June 1), 2007: pp 2331-2333 Downloaded from ascopubs.org by 3.88.211.217 on June 9, 2022 from 003.088.211.217 Copyright © 2022 American Society of Clinical Oncology. All rights reserved.