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

John Gerecitano, Carol Portlock, Paul Hamlin, Craig 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

Research output: Contribution to journalArticle

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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/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.

Original languageEnglish (US)
Pages (from-to)2493-2501
Number of pages9
JournalClinical Cancer Research
Volume17
Issue number8
DOIs
StatePublished - Apr 15 2011
Externally publishedYes

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Prednisone
Non-Hodgkin's Lymphoma
Cyclophosphamide
Appointments and Schedules
Vincristine
Mantle-Cell Lymphoma
Bortezomib
Rituximab
Research Design
Safety

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Phase I trial of weekly and twice-weekly bortezomib with rituximab, cyclophosphamide, and prednisone in relapsed or refractory non-hodgkin lymphoma. / Gerecitano, John; Portlock, Carol; Hamlin, Paul; Moskowitz, Craig; Noy, Ariela; Straus, David; Schulman, Philip; Dumitrescu, Otilia; Sarasohn, Debra; Pappanicholaou, Jennifer; Iasonos, Alexia; Zhang, Zhigang; Mo, Qianxing; Horanlli, Endri; Rojas, Celeste N.; Zelenetz, Andrew D.; O'Connor, Owen A.

In: Clinical Cancer Research, Vol. 17, No. 8, 15.04.2011, p. 2493-2501.

Research output: Contribution to journalArticle

Gerecitano, J, Portlock, C, Hamlin, P, Moskowitz, C, Noy, A, Straus, D, Schulman, P, Dumitrescu, O, Sarasohn, D, Pappanicholaou, J, Iasonos, A, Zhang, Z, Mo, Q, Horanlli, E, Rojas, CN, Zelenetz, AD & O'Connor, OA 2011, 'Phase I trial of weekly and twice-weekly bortezomib with rituximab, cyclophosphamide, and prednisone in relapsed or refractory non-hodgkin lymphoma', Clinical Cancer Research, vol. 17, no. 8, pp. 2493-2501. https://doi.org/10.1158/1078-0432.CCR-10-1498
Gerecitano, John ; Portlock, Carol ; Hamlin, Paul ; Moskowitz, Craig ; Noy, Ariela ; Straus, David ; Schulman, Philip ; Dumitrescu, Otilia ; Sarasohn, Debra ; Pappanicholaou, Jennifer ; Iasonos, Alexia ; Zhang, Zhigang ; Mo, Qianxing ; Horanlli, Endri ; Rojas, Celeste N. ; Zelenetz, Andrew D. ; O'Connor, Owen A. / Phase I trial of weekly and twice-weekly bortezomib with rituximab, cyclophosphamide, and prednisone in relapsed or refractory non-hodgkin lymphoma. In: Clinical Cancer Research. 2011 ; Vol. 17, No. 8. pp. 2493-2501.
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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/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.",
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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

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.

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