Phase I/II trial of a twice-daily regimen of temozolomide and celecoxib for treatment of relapsed/refractory glioblastoma multiforme and anaplastic astrocytoma

Abstract

1549 Background: Combination therapy using agents with different mechanisms of action and non-overlapping toxicity may be a safe and effective strategy in cancer therapy. As seen in Phase I of this trial, BID temozolomide [Temodar (TMZ)] in combination with celecoxib (Celebrex) is a safe treatment regimen for malignant glioma. Phase II of this clinical trial tests the hypothesis that celecoxib combined with a BID schedule of TMZ is a more effective therapy for recurrent/progressive malignant glioma. Methods: Patients received a loading dose of 200 mg/m2 of TMZ followed by 9 doses of 90 mg/m2 TMZ BID for 5 days of every 28 day cycle. Celecoxib was given to a maximum dose of 480 mg/m2 for 10 days. The regimen was well-tolerated by most patients. Hematologic toxicity was mild and did not recur following TMZ dose reduction. Results: 36 patients (22 M, 14 F) received 141 cycles of therapy. Interim responses were evaluated after 2 cycles. In the 29 patients evaluable for response, 5/29 (17%) had a partial response (PR), 21/29 (72.5%) had stable disease (SD), and 3/29 (10.5%) had progressive disease, resulting in an overall response rate of 90% at 2 months. One patient had a CR after 7 cycles. One patient had a PR for 13 cycles but developed spinal cord tumor. Average duration of response was 5.2 months (range, 2–13). The 6-month PFS for 23 evaluable patients was 8/23(35%) and 6-month overall survival rate of 19/23(83%). Conclusions: A regimen of twice-daily TMZ and celecoxib is a safe and potentially effective regimen for the treatment of recurrent high-grade glioma. Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Schering-Plough