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Phase I/II study of selective cyclooxygenase-2 inhibitor celecoxib as
a radiation sensitizer in patients with unresectable brain metastases Leandro C. A. Cerchietti,
Marcelo R. Bonomi, Alfredo H. Navigante, Monica A. Castro, Maria E. Cabalar
and Berta M. C. Roth
Translational Research Unit, Universidad
de Buenos Aires, Argentina [L.C.A.C., A.H.N., M.A.C.]. Department of Radiotherapy and Radiology,
Universidad de Buenos Aires, Argentina [M.R.B., B.M.C.R.]. Department of Internal Medicine,
Instituto de Oncologia Angel H. Roffo, Universidad de Buenos Aires,
Ciudad de Buenos Aires, Argentina [A.H.N.]. Albert Einstein Cancer Center, Chanin
Building, Room 517, 1300 Morris Park Avenue, Bronx, New York 10461,
USA [L.C.A.C.]. Correspondence to: Leandro C. A. Cerchietti,
Email: lcerchie@aecom.yu.edu, Phone: +1-718-430-4239, Fax: +1-718-430-8567.
Purpose. The primary goal of this phase I/II study was to
evaluate the feasibility, safety and efficacy of celecoxib
administered concomitant to radiotherapy to treat unresectable BM.
Patients
and methods. Patients with measurable BM by CT or MRI,
unresectability criteria by a neurosurgeon and RPA-RTOG class II were
eligible.
Celecoxib was administered at 400 mg/day during the
entire course of radiotherapy.
All patients were irradiated with 60Co
beams to whole-brain dose of 32 Gy (20 fractions of 1.6 Gy
each two times a day with a 6 h interval between treatments) followed
by a 22.4 Gy boost (same fractionation schedule) over evident
lesions.
Results. Twenty-seven patients were treated.
The
concurrent regimen was well tolerated with 15 cases of mild dyspepsia.
Alopecia (NCI grades 1–2) was the most important side effect.
Three
patients presented rash/desquamation of moderate intensity.
Radiological responses occurred in 18 of 25 valuable patients (72),
with five complete responses (CR).
Symptomatic responses were reported
in 25 of 27 patients (92.6), with 20 CR.
The overall response rate
(considering complete plus partial responses) was 66.7.
Percentile 50
for time-to-progression, time-to-neurological-progression and
functional-independence-time were 3, 6.25 and 6.7 months,
respectively. Median survival time was 8.7 months.
Conclusion.
Our initial results suggest that radiotherapy plus celecoxib is safe
and a possible active treatment for patients with BM.
Further
investigation in a randomized trial is warranted to validate its
clinical utility.
Keywords: brain
metastases - celecoxib - cyclooxygenase - radiation - radiosensitizer
This Article was presented in part at the Second
International Conference on Translational Research and Preclinical
Strategies in Radiation Oncology, March 2003, Lugano, Switzerland.
© Springer 2005
Source: http://springerlink.metapress.com/openurl.asp?genre=article&eissn=1573-7373&volume=71&issue=1&spage=73
DOI: http://dx.doi.org/10.1007/s11060-004-9179-x
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