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-kappaB) appears to play in the pathogenesis of this tumor, the ability of bortezomib to inhibit NF-kappaB 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.


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.
Mendler
J H
JH
Department of Internal Medicine, James P Wilmot Cancer Center, University of Rochester Medical Center, Rochester, NY 14642, USA.
Kelly
J
J
Voci
S
S
Marquis
D
D
Rich
L
L
Rossi
R M
RM
Bernstein
S H
SH
Jordan
C T
CT
Liesveld
J
J
Fisher
R I
RI
Friedberg
J W
JW
D000328:Adult; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D001897:Boronic Acids / Q000008:administration & dosage / Q000009:adverse effects; D000069286:Bortezomib; D003841:Deoxycytidine / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives; D005260:Female; D006689:Hodgkin Disease / Q000188:drug therapy* / Q000201:enzymology; D006801:Humans; D008297:Male; D008875:Middle Aged; D046988:Proteasome Endopeptidase Complex / Q000097:blood; D011719:Pyrazines / Q000008:administration & dosage / Q000009:adverse effects; D000093542:Gemcitabine
D001897:Boronic Acids; D011719:Pyrazines; D003841:Deoxycytidine; D000069286:Bortezomib; D046988:Proteasome Endopeptidase Complex; D000093542:Gemcitabine