|
|
In
Reply:
Jeremy N. Rich1, Henry S. Friedman1, James
B. Powell, Jr1, Janet E. Dancey2
1Duke University, Durham, NC.
2National Cancer Institute, Bethesda, MD
We appreciate the issues
raised by Drs M. Raphael Pfeffer, Mark L. Levitt, and Dan Aderka
regarding the efficacy of gefitinib for patients with recurrent
glioblastomas. [1]
Drs Pfeffer, Levitt, and Aderka raised concerns that the conclusion
in the abstract stated that gefitinib "has activity" and
that this does not reflect the fact that a minority of patients
achieved a 6-month progression-free survival.
We agree that gefitinib
has limited efficacy at the doses used in the current trial in a
patient population not selected for target expression and pathway
activation.
In fact, our initial manuscript concluded, "Gefitinib is well
tolerated and has modest activity in patients with recurrent
glioblastoma."
In the review process, we were advised to alter the manuscript:
"In your revision addressing the issues raised by the reviewer,
we agree that the word ‘modest’ is perhaps either too subjective
or overly optimistic; it might be better to say that the drug ‘has
activity’ and let further trials quantify it."
The published manuscript reflects this change.
We remain confident that
gefitinib does have activity in a subset of patients.
At this time, we still have two patients with well controlled disease
on this trial after 72 and 99 weeks.
Although the extent of surgical resection has a benefit in patients
with glioblastomas
[2],
the durable stability
of disease seen in the minority of patients suggests gefitinib may
benefit these patients.
Given our current understanding of the role of EGFR amplification and
EGFR and PTEN mutations in glioblastoma, and the role of PTEN
in resistance to EGFR inhibition [3,4],
gefitinib represents a novel therapy that at higher doses and perhaps
in combination with other therapies may offer benefit in a defined
population of glioblastoma patients.
Clearly, physicians and
patients in consultation with their caregivers should read fully the
results and discussion of any manuscript before adoption of a
therapy.
Further preclinical and clinical studies will likely be required to
optimally use gefitinib in patients with glioblastoma.
Authors'
Disclosures of Potential Conflicts of Interest
The authors
indicated no potential conflicts of interest.
References
[1] Rich JN, Reardon DA,
Peery T, et al: Phase II trial of gefitinib in recurrent glioblastoma. J Clin
Oncol 22:133-142, 2004[Abstract/Free
Full Text]
[2] Lacroix
M, Abi-Said D, Fourney DR, et al: A multivariate analysis of 416 patients with
glioblastoma multiforme: Prognosis, extent of resection, and survival. J
Neurosurg 95:190-198, 2001
[3] She QB, Solit D, Basso
A, et al: Resistance to gefitinib in PTEN-null HER-overexpressing tumor cells
can be overcome through restoration of PTEN function or pharmacologic modulation
of constitutive phosphatidylinositol 3'-kinase/Akt pathway signaling. Clin
Cancer Res 9:4340-4346, 2003[Abstract/Free
Full Text]
[4] Bianco R, Shin I,
Ritter CA, et al: Loss of PTEN/MMAC1/TEP in EGF receptor-expressing tumor cells
counteracts the antitumor action of EGFR tyrosine kinase inhibitors. Oncogene
22:2812-2822, 2003[CrossRef][Medline]
© 2004 American
Society for Clinical Oncology
|
