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In Reply:

The Preston Robert Tisch Brain Tumor Center; and the Departments of Surgery, Medicine, Biostatistics, Pediatrics, Neurobiology, and Pathology, Duke University Medical Center, Durham, NC

We would like to reply to the letter from Marc Chamberlain regarding our article entitled "Bevacizumab Plus Irinotecan in Recurrent Glioblastoma." Chamberlain raises a number of important issues and makes many good points.

The first issue was the schedule of irinotecan. We chose a regimen of administration once every 2 weeks with both irinotecan and bevacizumab to limit the toxicity. The regimen of administration once every 3 weeks may be simpler, but the dose of irinotecan will be increased and we did not want to stop the trial because of toxicity. With our experience, the schedule of administration once every 3 weeks for irinotecan and bevacizumab may be as efficacious and tolerable.

The second issue raised by Chamberlain is the use of irinotecan in this regimen. We combined irinotecan with bevacizumab for three reasons. The first reason is that chemotherapy and bevacizumab is more active than bevacizumab alone in most malignancies. The second reason was that irinotecan has a different mechanism of action than temozolomide, so we were trying to limit cross-resistance. The third reason for combining irinotecan with bevacizumab is the experience in colorectal carcinoma and the US Food and Drug Administration approval of irinotecan and bevacizumab. I agree with Chamberlain that alternative cytotoxic chemotherapies may be equally active, and we eagerly await the results of ongoing clinical trials. All of these patients had received temozolomide and radiation therapy, and we hypothesize that irinotecan and bevacizumab would be efficacious in an O⁶-methylguanine-DNA methyltransferase–unfavorable tumor.

The third issue that Chamberlain raises was the pharmacoeconomics of anticancer therapy. We agree that the pharmacoeconomics of cancer care is a contentious issue and needs to be addressed. We feel fortunate that we finally have an active regimen against recurrent glioblastoma that allows us to worry about pharmacoeconomics.

The final issue raised by Chamberlain was craniotomy site wound dehiscence. We agree that this is a potential problem, and the concurrent administration of antiangiogenic agents and dexamethasone may increase the risk of wound dehiscence. We have had some patients with craniotomy site dehiscence as well as dehiscence of their port-a-cath sites. The issue of wound dehiscence requires extensive patient and provider education, and is one of the potential limitations of this promising therapy.

We appreciate Chamberlain's comments, and hope that the combination of irinotecan and bevacizumab is the beginning of a new wave of therapies for malignant gliomas.

AUTHORS’ DISCLOSURES OF POTENTIAL CONFLICTS OF INTEREST

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

ACKNOWLEDGMENTS

Supported by Grants No. 5 P50 CA108796, 5 P50 NS20023, and 4 R37 CA11898 from the National Institutes of Health, Department of Health and Human Services, Bethesda, MD; The Preston Robert Tisch Brain Tumor Research Fund; and the Bryan Cless Research Fund. J.N.R. is a Damon Runyon-Lilly Clinical Investigator.

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Related Correspondence

• Bevacizumab Plus Irinotecan in Recurrent Glioblastoma
  Marc C. Chamberlain
  JCO 2008 26: 1012-1013 [Full Text]

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