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In Reply

Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA

Charles S. Fuchs

Department of Medical Oncology, Dana-Farber Cancer Institute and the Channing Laboratory, Brigham and Women's Hospital, Boston, MA

We thank Dr Fabregat and colleagues for their thoughtful comments regarding our study.¹ In light of initial reports of tumor shrinkage associated with recombinant human endostatin (rhEndostatin) in both animal and phase I studies, our phase II trial with this agent was designed to evaluate antitumor activity using traditional response criteria. Given the absence of clearly demonstrated antitumor activity with these criteria, we retrospectively evaluated and reported progression intervals before and after rhEndostatin administration, to assess whether rhEndostatin may have had a cytostatic effect. This determination was limited not only by natural variability in the rates of tumor progression between patients enrolled on the study, but also by differences in the time intervals at which patients underwent radiologic evaluation before and after study entry. In this evaluation, however, half (48%) of the assessable patients had stable disease (as measured by WHO criteria) for at least 6 months before study enrollment. The median progression-free survival time during treatment with rhEndostatin (5.8 months) was nearly identical to this value, suggesting (but not proving) that rhEndostatin had little effect on tumor growth.

Traditional tumor responses, as measured by Response Evaluation Criteria in Solid Tumors, have recently been reported after the administration of either bevacizumab or sunitinib in patients with advanced neuroendocrine tumors. The confirmed evidence of tumor shrinkage in a subset of patients receiving these agents suggests that they may have more antitumor activity than does rhEndostatin, although we concur with the authors that differences in response criteria, together with potential differences in patient selection, preclude definitive comparisons between the studies.

Nontoxic agents that slow or prevent tumor progression would be welcome in the treatment of patients with neuroendocrine tumors. Single-arm phase II designs are poorly suited to evaluate this type of effect, and even with uniform inclusion criteria, cannot be used to draw definitive comparisons between different agents. Randomized designs using progression-free survival end points should be strongly considered in future neuroendocrine tumor trials.

AUTHORS' DISCLOSURES OF POTENTIAL CONFLICTS OF INTEREST

Although all authors completed the disclosure declaration, the following author(s) indicated a financial or other interest that is relevant to the subject matter under consideration in this article. Certain relationships marked with a "U" are those for which no compensation was received; those relationships marked with a "C" were compensated. For a detailed description of the disclosure categories, or for more information about ASCO's conflict of interest policy, please refer to the Author Disclosure Declaration and the Disclosures of Potential Conflicts of Interest section in Information for Contributors.

Employment or Leadership Position: None Consultant or Advisory Role: Charles Fuchs, Roche (C), Genentech (C), Amgen (C), Bristol Myers-Squibb (C), Astra-Zeneca (C), Sanofi-Aventis (C), Pfizer (C) Stock Ownership: None Honoraria: Matthew H. Kulke, Novartis Research Funding: None Expert Testimony: None Other Remuneration: None

REFERENCE

1. Kulke MH, Bergsland EK, Ryan DP, et al: Phase II study of recombinant human endostatin in patients with advanced neuroendocrine tumors. J Clin Oncol 24:3555-3561, 2006[Abstract/Free Full Text]

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This Article Full Text (PDF) Purchase Article View Shopping Cart Alert me when this article is cited Alert me if a correction is posted Services Email this article to a colleague Similar articles in this journal Alert me to new issues of the journal Save to my personal folders Download to citation manager Rights & Permissions Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Kulke, M. H. Articles by Fuchs, C. S. Search for Related Content PubMed Articles by Kulke, M. H. Articles by Fuchs, C. S. Social Bookmarking                            What's this?