Bortezomib and gemcitabine in relapsed or refractory Hodgkin's lymphoma

Background: Given the significant activity and tolerability of gemcitabine in patients with relapsed Hodgkin's lymphoma (HL), the critical role that nuclear factor kappa B (NF-kappa B) appears to play in the pathogenesis of this tumor, the ability of bortezomib to inhibit NF-kappa B 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 methods: A total of 18 patients participated. Patients received 3-week cycles of bortezomib 1 mg/m(2) on days 1, 4, 8, and 11 plus gemcitabine 800 mg/m(2) on days 1 and 8. Results: The 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. Conclusions: The 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.