TY - JOUR
T1 - Phase I trial of weekly and twice-weekly bortezomib with rituximab, cyclophosphamide, and prednisone in relapsed or refractory non-hodgkin lymphoma
AU - Gerecitano, John
AU - Portlock, Carol
AU - Hamlin, Paul
AU - Moskowitz, Craig H.
AU - Noy, Ariela
AU - Straus, David
AU - Schulman, Philip
AU - Dumitrescu, Otilia
AU - Sarasohn, Debra
AU - Pappanicholaou, Jennifer
AU - Iasonos, Alexia
AU - Zhang, Zhigang
AU - Mo, Qianxing
AU - Horanlli, Endri
AU - Rojas, Celeste N.
AU - Zelenetz, Andrew D.
AU - O'Connor, Owen A.
PY - 2011/4/15
Y1 - 2011/4/15
N2 - Purpose: To determine the safety and efficacy of substituting weekly or twice-weekly bortezomib for vincristine in the R-CVP (rituximab, cyclophosphamide, vincristine, and prednisone) regimen in patients with relapsed/refractory indolent and mantle cell lymphoma (MCL). Experimental Design: Of the 57 patients in this phase I trial, 55 participated in 1 of 2 dosing schedules that included rituximab (375 mg/m2) and cyclophosphamide (750 or 1,000 mg/m2) administered on day 1 of each 21-day cycle and prednisone (100 mg orally) days 2 to 6. In the once-weekly schedule, bortezomib was administered on days 2 and 8; on the twice-weekly schedule, bortezomib was given on days 2, 5, 9, and 12. Bortezomib and cyclophosphamide were alternately escalated. A separate cohort of 10 patients in the twice-weekly schedule received concurrent pegfilgrastim (PegG) on day 2. Results: Both schedules of R-CBorP (rituximab, cyclophosphamide, bortezomib, and prednisone) were well tolerated. Most toxicities across all dose levels and cycles were grade 1 or 2. The overall response rates for patients on the weekly (n= 13) and twice-weekly (n = 33) schedules were 46% [23% complete response/complete response unconfirmed (CR/CRu)] and 64% (36% CR/CRu), respectively. Concurrent PegG did not increase hematologic toxicities in this regimen. A randomized phase II study is under way to further compare toxicity and efficacy of the 2 dosing schedules. Conclusions: R-CBorP is a safe and effective regimen in patients with relapsed/refractory indolent and MCLs. Most toxicities were grade 1 or 2, and a promising response rate was seen in this phase I study.
AB - Purpose: To determine the safety and efficacy of substituting weekly or twice-weekly bortezomib for vincristine in the R-CVP (rituximab, cyclophosphamide, vincristine, and prednisone) regimen in patients with relapsed/refractory indolent and mantle cell lymphoma (MCL). Experimental Design: Of the 57 patients in this phase I trial, 55 participated in 1 of 2 dosing schedules that included rituximab (375 mg/m2) and cyclophosphamide (750 or 1,000 mg/m2) administered on day 1 of each 21-day cycle and prednisone (100 mg orally) days 2 to 6. In the once-weekly schedule, bortezomib was administered on days 2 and 8; on the twice-weekly schedule, bortezomib was given on days 2, 5, 9, and 12. Bortezomib and cyclophosphamide were alternately escalated. A separate cohort of 10 patients in the twice-weekly schedule received concurrent pegfilgrastim (PegG) on day 2. Results: Both schedules of R-CBorP (rituximab, cyclophosphamide, bortezomib, and prednisone) were well tolerated. Most toxicities across all dose levels and cycles were grade 1 or 2. The overall response rates for patients on the weekly (n= 13) and twice-weekly (n = 33) schedules were 46% [23% complete response/complete response unconfirmed (CR/CRu)] and 64% (36% CR/CRu), respectively. Concurrent PegG did not increase hematologic toxicities in this regimen. A randomized phase II study is under way to further compare toxicity and efficacy of the 2 dosing schedules. Conclusions: R-CBorP is a safe and effective regimen in patients with relapsed/refractory indolent and MCLs. Most toxicities were grade 1 or 2, and a promising response rate was seen in this phase I study.
UR - http://www.scopus.com/inward/record.url?scp=79954614811&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=79954614811&partnerID=8YFLogxK
U2 - 10.1158/1078-0432.CCR-10-1498
DO - 10.1158/1078-0432.CCR-10-1498
M3 - Article
C2 - 21346146
AN - SCOPUS:79954614811
VL - 17
SP - 2493
EP - 2501
JO - Clinical Cancer Research
JF - Clinical Cancer Research
SN - 1078-0432
IS - 8
ER -