A phase I/II trial of bortezomib combined concurrently with gemcitabine for relapsed or refractory DLBCL and peripheral T-cell lymphomas.
There remains an unmet therapeutic need for patients with relapsed/refractory diffuse large B-cell lymphoma (DLBCL) and peripheral T-cell lymphoma (PTCL). We conducted a phase I/II trial with bortezomib (dose-escalated to 1·6 mg/m(2) ) given concurrently with gemcitabine (800 mg/m(2) ) days 1 + 8 q21 d. Of 32 patients, 16 each had relapsed/refractory PTCL and DLBCL. Median prior therapies were 3 and 35% had failed transplant. Among the first 18 patients, 67% experienced grade 3/4 neutropenia and/or grade 3/4 thrombocytopenia resulting in repeated treatment delays (relative dose intensity: 46%). Thus, the study was amended to give bortezomib and gemcitabine days 1 + 15 q28 d, which resulted in markedly improved tolerability. Among all patients, the overall response rate (ORR) was 24% with 19% complete remission (CR; intent-to-treat (ITT) ORR 16%, CR 13%), which met criteria for futility. The ORR for DLBCL was 10% (CR 10%) vs. 36% for PTCL (CR 27%). Among 6 PTCL patients treated on the modified schedule, ORR by ITT was 50% (CR 30%). Altogether, concurrent bortezomib/gemcitabine given days 1 + 8 q21 d was not tolerable, while modification to a bi-monthly schedule allowed consistent treatment delivery. Whereas efficacy of this combination was low in heavily pre-treated DLBCL, there was a signal of activity in relapsed/refractory PTCL utilizing the modified schedule.
Division of Hematology/Oncology, Tufts University School of Medicine, Boston, MA, USA.
Andrew M
AM
Evens
Steven T
ST
Rosen
Irene
I
Helenowski
Justin
J
Kline
Annette
A
Larsen
Jennifer
J
Colvin
Jane N
JN
Winter
Koen M
KM
van Besien
Leo I
LI
Gordon
Sonali M
SM
Smith
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D001897:Boronic Acids / Q000008:administration & dosage; D000069286:Bortezomib; D003841:Deoxycytidine / Q000008:administration & dosage / Q000031:analogs & derivatives; D005260:Female; D006801:Humans; D016403:Lymphoma, Large B-Cell, Diffuse / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D016411:Lymphoma, T-Cell, Peripheral / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D008297:Male; D008875:Middle Aged; D011719:Pyrazines / Q000008:administration & dosage; D012008:Recurrence; D016896:Treatment Outcome; D000093542:Gemcitabine
D001897:Boronic Acids; D011719:Pyrazines; D003841:Deoxycytidine; D000069286:Bortezomib; D000093542:Gemcitabine
bortezomib; diffuse large B-cell lymphoma; gemcitabine; lymphoma; peripheral T-cell lymphoma