Phase I trial of weekly and twice-weekly bortezomib with rituximab, cyclophosphamide, and prednisone in relapsed or refractory non-Hodgkin lymphoma.

Abstract

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/m(2)) and cyclophosphamide (750 or 1,000 mg/m(2)) 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.

• Authors: John Gerecitano, Carol Portlock, Paul Hamlin, Craig H Moskowitz, Ariela Noy, David Straus, Philip Schulman, Otilia Dumitrescu, Debra Sarasohn, Jennifer Pappanicholaou, Alexia Iasonos, Zhigang Zhang, Qianxing Mo, Endri Horanlli, Celeste N Rojas, Andrew D Zelenetz, Owen A O'Connor
• Journal: Clinical cancer research : an official journal of the American Association for Cancer Research (Clin Cancer Res) Vol. 17 Issue 8 Pg. 2493-501 (Apr 15 2011) ISSN: 1557-3265 [Electronic] United States
• PMID: 21346146 (Publication Type: Clinical Trial, Phase I, Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: ©2011 AACR.

Chemical References

• Antibodies, Monoclonal, Murine-Derived
• Boronic Acids
• Pyrazines
• Rituximab
• Bortezomib
• Cyclophosphamide
• Prednisone

Topics

• Anemia (chemically induced)
• Antibodies, Monoclonal, Murine-Derived (administration & dosage, adverse effects)
• Antineoplastic Combined Chemotherapy Protocols (adverse effects, therapeutic use)
• Boronic Acids (administration & dosage, adverse effects)
• Bortezomib
• Cyclophosphamide (administration & dosage, adverse effects)
• Diarrhea (chemically induced)
• Drug Administration Schedule
• Drug Resistance, Neoplasm
• Fatigue (chemically induced)
• Female
• Fever (chemically induced)
• Follow-Up Studies
• Humans
• Leukopenia (chemically induced)
• Lymphoma, Non-Hodgkin (drug therapy, pathology)
• Male
• Middle Aged
• Nausea (chemically induced)
• Prednisone (administration & dosage, adverse effects)
• Pyrazines (administration & dosage, adverse effects)
• Recurrence
• Rituximab
• Treatment Outcome