Phase I/II study of selective cyclooxygenase-2 inhibitor celecoxib as a radiation sensitizer in patients with unresectable brain metastases.

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.