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 Co-60 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.