Medline ® Abstract for Reference 154
of 'Overview of neurologic complications of non-platinum cancer chemotherapy'
A multicenter phase II trial of thalidomide and celecoxib for patients with relapsed and refractory multiple myeloma.
Prince HM, Mileshkin L, Roberts A, Ganju V, Underhill C, Catalano J, Bell R, Seymour JF, Westerman D, Simmons PJ, Lillie K, Milner AD, Iulio JD, Zeldis JB, Ramsay R
Clin Cancer Res. 2005;11(15):5504.
Preclinical data indicates that cyclooxygenase-2 (COX-2) inhibition impairs plasma cell growth and potentially synergizes with thalidomide. We performed a trial in previously treated patients with myeloma using thalidomide up to a maximum dose of 800 mg/d with celecoxib (400 mg bid). Outcomes were compared with a prior trial of thalidomide. Sixty-six patients with median age of 67 (range, 43-85) received a median dose of thalidomide and celecoxib of 400 and 800 mg/d, respectively, with median durations of treatment of 27 and 13 weeks, respectively. The most common toxicities associated with premature discontinuation of celecoxib (n = 30 of 53, 57%) were fluid retention and deterioration of renal function. Overall response rate (RR) was 42% and with 20 months median follow-up; the actuarial median progression-free survival and overall survival were 6.8 and 21.4 months, respectively. Unlike our prior study, age>65 years was not predictive of inferior RR due to improvement in RR in older patients with the combination (37% versus 15%, P = 0.08). The RR was superior in patients who received a total dose of celecoxib exceeding 40 g in the first 8 weeks of therapy (62% versus 30%, P = 0.021). Progression-freesurvival and overall survival were also improved. Other predictors for inferior progression-free survival were age>65 years (P = 0.016) and elevated beta(2)-microglobulin (P = 0.017). This study provides evidence that the addition of high-dose celecoxib adds to the antimyeloma activity of thalidomide but this comes with unacceptable toxicity. Future studies should use newer COX-2 inhibitors with thalidomide, or their respective derivatives.
University of Melbourne and Department of Haematology, Peter MacCallum Cancer Centre, East Melbourne, Victoria, Australia. Miles.Prince@petermac.org