Originally published as JCO Early Release 10.1200/JCO.2008.21.6143 on March 2 2009

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In Reply

Department of Surgery, Duke University Medical Center, Durham, NC

In Reply

On behalf of my coauthors, I wish to thank Chamberlain¹ for the important issues he raised regarding our recently reported trial,² in which patients with glioblastoma (GBM) were randomly assigned at first recurrence to receive single-agent cilengitide, an _vβ₃/_vβ₅ integrin inhibitor, at either 500 mg or 2,000 mg twice weekly. The first important question raised by Chamberlain was why we chose to design our study to evaluate outcome against that reported with temozolomide,³ rather than outcomes reported in a series of salvage phase II studies.^4,5 We chose the comparative benchmark achieved with temozolomide for two reasons. First, a more favorable outcome was achieved in the temozolomide study, thus setting a higher bar of comparison. Second, our study, like the temozolomide study, was limited to patients with GBM at first recurrence, in contrast to the series of phase II studies suggested by Chamberlain, which included patients with disease that had progressed beyond first recurrence.

Chamberlain also questioned whether our study² had achieved sufficiently positive results to justify additional evaluation of cilengitide as treatment for patients with recurrent GBM. Unfortunately, our study was not designed to define outcome relative to an established salvage regimen. Nonetheless, we did observe encouraging evidence of antitumor activity, particularly among patients treated at the cilengitide dose level of 2,000 mg. In these patients, we noted a radiographic response rate and median overall survival that surpassed those achieved with temozolomide, and a 6-month progression-free survival rate that was within the 95% CI achieved with temozolomide.³ In addition, we feel that these results have additional significance because they were achieved in patients who had progressive disease after receiving temozolomide therapy.

Finally, Chamberlain questioned the impact of bevacizumab therapy and methylguanine methyltransferase (MGMT) status on outcome in patients treated on our study.² Regarding the former, none of the patients treated on our study received bevacizumab therapy. Second, MGMT status was not assessed, because our study was conducted before the link between response to cilengitide therapy and MGMT status had been reported.⁶ Nonetheless, we agree with Chamberlain that in future cilengitide studies, both bevacizumab therapy and MGMT status will need to be considered in the interpretation of overall study results.

AUTHOR'S DISCLOSURES OF POTENTIAL CONFLICTS OF INTEREST

The author(s) indicated no potential conflicts of interest.

REFERENCES

1. Chamberlain MC: Cilengitide: Does it really represent a new targeted therapy for recurrent glioblastoma? J Clin Oncol 27:1921; 2009.[Free Full Text]

2. Reardon DA, Fink KL, Mikkelsen T, et al: Randomized phase II study of cilengitide, an integrin-targeting arginine-glycine-aspartic acid peptide, in recurrent glioblastoma multiforme. J Clin Oncol 26:5610–5617, 2008.[Abstract/Free Full Text]

3. Yung WK, Albright RE, Olson J, et al: A phase II study of temozolomide vs. procarbazine in patients with glioblastoma multiforme at first relapse. Br J Cancer 83:588–593, 2000.[CrossRef][Medline]

4. Wong ET, Hess KR, Gleason MJ, et al: Outcomes and prognostic factors in recurrent glioma patients enrolled onto phase II clinical trials. J Clin Oncol 17:2572–2578, 1999.[Abstract/Free Full Text]

5. Lamborn KR, Yung WK, Chang SM, et al: Progression-free survival: An important end point in evaluating therapy for recurrent high-grade gliomas. Neuro Oncol 10:162–170, 2008.

6. Stupp R, Goldbrunner R, Neyns B, et al: Phase I/IIa trial of cilengitide (EMD121974) and temozolomide with concomitant radiotherapy, followed by temozolomide and cilengitide maintenance therapy in patients (pts) with newly diagnosed glioblastoma (GBM). J Clin Oncol 25:75s; 2007 (suppl) abstr 2000.

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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 Reardon, D. A. Search for Related Content PubMed Articles by Reardon, D. A. Related Articles Related Article Related Correspondence Social Bookmarking                            What's this?