Bortezomib and gemcitabine in relapsed or refractory Hodgkin's lymphoma

Abstract

BackgroundGiven the significant activity and tolerability of gemcitabine in patients with relapsed Hodgkin's lymphoma (HL), the critical role that nuclear factor kappa B (NF-κB) appears to play in the pathogenesis of this tumor, the ability of bortezomib to inhibit NF-κB activity, and laboratory studies suggesting synergistic antitumor effects of gemcitabine and bortezomib, we hypothesized that this combination would be efficacious in patients with relapsed or refractory HL. Patients and methodsA total of 18 patients participated. Patients received 3-week cycles of bortezomib 1 mg/m2 on days 1, 4, 8, and 11 plus gemcitabine 800 mg/m2 on days 1 and 8. ResultsThe overall response rate for all patients was 22% (95% confidence interval 3% to 42%). Three patients developed grade III transaminase elevation: one was removed from the study and two had doses of gemcitabine held. Almost all patients exhibited inhibition of proteasome activity with treatment. ConclusionsThe combination of gemcitabine and bortezomib is a less active and more toxic regimen in relapsed HL than other currently available treatments. It poses a risk of severe liver toxicity and should be pursued with caution in other types of cancer.