Palliation of relapsed aggressive histology NHL with high-dose celecoxib and 'metronomic' low-dose cyclophosphamide

3016 Background: Relapsed aggressive Non-Hodgkin's Lymphoma (NHL) has a poor prognosis; and new treatments are needed. Angiogenesis is increased in aggressive NHL, and may be a target in these diseases. Low dose chronic chemotherapy (metronomic chemotherapy, MC) inhibits angiogenesis in vitro. Since COX-2 may promote neoplasia and tumour angiogenesis, selective COX-2 inhibitors may have anti-tumour effects in NHL.We assessed response to MC and COX-2 inhibition and toxicity in patients (pts) with relapsed aggressive NHL following anthracycline based chemotherapy. Methods: Pts with measureable disease and normal renal function received cyclophosphamide 50 mg po qd + celecoxib 400 mg po bid. Pts were assessed clinically monthly x 6 then q 2 mos; CT scans q 3 mos, serial plasma VEGF and TSP-1 levels. Pharmacokinetics (PK)and serial LN biopsies for COX-2 IHC were performed in selected pts. Serial circulating endothelial cells (CEC) and their precursors (CEP) were measured by flow cytometry. Results: To date 21...