Phase 1 trial of bortezomib plus R-CHOP in previously untreated patients with aggressive non-Hodgkin lymphoma

Richard R. Furman, Peter Martin, Jia Ruan, Ying Kuen K Cheung, Julie Marie Vose, Ann S. Lacasce, Rebecca Elstrom, Morton Coleman, John P. Leonard

Research output: Contribution to journalArticle

44 Citations (Scopus)

Abstract

Background: Bortezomib has preclinical and clinical in B-cell lymphomas, both alone and in combination with other agents. A phase 1 evaluation was conducted of bortezomib with rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) in patients with untreated diffuse large B-cell lymphoma (DLBCL) or mantle cell lymphoma (MCL). Methods: Twenty patients (16 with DLBCL and 4 with MCL) with a median age of 66 years (range, 29-84 years) were enrolled. Eleven subjects (55%) had an elevated lactate dehydrogenase level, and 10 patients (50%) had International Prognostic Index scores of 3 to 5. Standard R-CHOP was administered on a 21-day cycle for 6 cycles, with 1 of 3 dose levels of bortezomib (0.7 mg/m2 [n = 4 patients], 1.0 mg/m2 [n = 9 patients], or 1.3 mg/m2 [n = 7 patients]) administered on Days 1 and 4 of each cycle. Results: The maximum tolerated dose of bortezomib with R-CHOP was not reached, and the 1.3-mg/m 2 dose level had acceptable tolerability. A dose-limiting toxicity (pulmonary) was only observed in 1 patient receiving 1.0 mg/m2 of bortezomib. Neuropathy occurred in 13 patients (65%), but was mostly grade 1 (45%) and reached grade 3 in only 1 patient (all toxicities were graded using the Common Terminology Criteria for Adverse Events, version 3.0). Grade 4 hematologic toxicity occurred in 7 patients (35%). Of 19 evaluable patients, all responded, with 18 (95%) cases of complete response/complete response unconfirmed achieved and 1 (5%) partial response reported. At a median follow-up of 56 months, overall survival at 4 years was 75% and progression-free survival was 58%. Conclusions: Bortezomib at a dose of 1.3 mg/m2 twice per cycle can be added to R-CHOP chemotherapy with acceptable toxicity. Multi-institutional and cooperative group follow-up studies of this regimen are currently ongoing. Cancer 2010.

Original languageEnglish (US)
Pages (from-to)5432-5439
Number of pages8
JournalCancer
Volume116
Issue number23
DOIs
StatePublished - Dec 1 2010

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Non-Hodgkin's Lymphoma
Mantle-Cell Lymphoma
Bortezomib
Maximum Tolerated Dose
Lymphoma, Large B-Cell, Diffuse
Vincristine
B-Cell Lymphoma
Prednisone
L-Lactate Dehydrogenase
Terminology
Doxorubicin
Cyclophosphamide
Disease-Free Survival
B-Lymphocytes
Lung
Survival

Keywords

  • and prednisone (CHOP)
  • bortezomib
  • cyclophosphamide
  • diffuse large B-cell lymphoma
  • doxorubicin
  • mantle cell lymphoma
  • maximum tolerated dose
  • non-Hodgkin lymphoma
  • rituximab
  • toxicity
  • vincristine

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Furman, R. R., Martin, P., Ruan, J., Cheung, Y. K. K., Vose, J. M., Lacasce, A. S., ... Leonard, J. P. (2010). Phase 1 trial of bortezomib plus R-CHOP in previously untreated patients with aggressive non-Hodgkin lymphoma. Cancer, 116(23), 5432-5439. https://doi.org/10.1002/cncr.25509

Phase 1 trial of bortezomib plus R-CHOP in previously untreated patients with aggressive non-Hodgkin lymphoma. / Furman, Richard R.; Martin, Peter; Ruan, Jia; Cheung, Ying Kuen K; Vose, Julie Marie; Lacasce, Ann S.; Elstrom, Rebecca; Coleman, Morton; Leonard, John P.

In: Cancer, Vol. 116, No. 23, 01.12.2010, p. 5432-5439.

Research output: Contribution to journalArticle

Furman, RR, Martin, P, Ruan, J, Cheung, YKK, Vose, JM, Lacasce, AS, Elstrom, R, Coleman, M & Leonard, JP 2010, 'Phase 1 trial of bortezomib plus R-CHOP in previously untreated patients with aggressive non-Hodgkin lymphoma', Cancer, vol. 116, no. 23, pp. 5432-5439. https://doi.org/10.1002/cncr.25509
Furman, Richard R. ; Martin, Peter ; Ruan, Jia ; Cheung, Ying Kuen K ; Vose, Julie Marie ; Lacasce, Ann S. ; Elstrom, Rebecca ; Coleman, Morton ; Leonard, John P. / Phase 1 trial of bortezomib plus R-CHOP in previously untreated patients with aggressive non-Hodgkin lymphoma. In: Cancer. 2010 ; Vol. 116, No. 23. pp. 5432-5439.
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abstract = "Background: Bortezomib has preclinical and clinical in B-cell lymphomas, both alone and in combination with other agents. A phase 1 evaluation was conducted of bortezomib with rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) in patients with untreated diffuse large B-cell lymphoma (DLBCL) or mantle cell lymphoma (MCL). Methods: Twenty patients (16 with DLBCL and 4 with MCL) with a median age of 66 years (range, 29-84 years) were enrolled. Eleven subjects (55{\%}) had an elevated lactate dehydrogenase level, and 10 patients (50{\%}) had International Prognostic Index scores of 3 to 5. Standard R-CHOP was administered on a 21-day cycle for 6 cycles, with 1 of 3 dose levels of bortezomib (0.7 mg/m2 [n = 4 patients], 1.0 mg/m2 [n = 9 patients], or 1.3 mg/m2 [n = 7 patients]) administered on Days 1 and 4 of each cycle. Results: The maximum tolerated dose of bortezomib with R-CHOP was not reached, and the 1.3-mg/m 2 dose level had acceptable tolerability. A dose-limiting toxicity (pulmonary) was only observed in 1 patient receiving 1.0 mg/m2 of bortezomib. Neuropathy occurred in 13 patients (65{\%}), but was mostly grade 1 (45{\%}) and reached grade 3 in only 1 patient (all toxicities were graded using the Common Terminology Criteria for Adverse Events, version 3.0). Grade 4 hematologic toxicity occurred in 7 patients (35{\%}). Of 19 evaluable patients, all responded, with 18 (95{\%}) cases of complete response/complete response unconfirmed achieved and 1 (5{\%}) partial response reported. At a median follow-up of 56 months, overall survival at 4 years was 75{\%} and progression-free survival was 58{\%}. Conclusions: Bortezomib at a dose of 1.3 mg/m2 twice per cycle can be added to R-CHOP chemotherapy with acceptable toxicity. Multi-institutional and cooperative group follow-up studies of this regimen are currently ongoing. Cancer 2010.",
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T1 - Phase 1 trial of bortezomib plus R-CHOP in previously untreated patients with aggressive non-Hodgkin lymphoma

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AU - Martin, Peter

AU - Ruan, Jia

AU - Cheung, Ying Kuen K

AU - Vose, Julie Marie

AU - Lacasce, Ann S.

AU - Elstrom, Rebecca

AU - Coleman, Morton

AU - Leonard, John P.

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N2 - Background: Bortezomib has preclinical and clinical in B-cell lymphomas, both alone and in combination with other agents. A phase 1 evaluation was conducted of bortezomib with rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) in patients with untreated diffuse large B-cell lymphoma (DLBCL) or mantle cell lymphoma (MCL). Methods: Twenty patients (16 with DLBCL and 4 with MCL) with a median age of 66 years (range, 29-84 years) were enrolled. Eleven subjects (55%) had an elevated lactate dehydrogenase level, and 10 patients (50%) had International Prognostic Index scores of 3 to 5. Standard R-CHOP was administered on a 21-day cycle for 6 cycles, with 1 of 3 dose levels of bortezomib (0.7 mg/m2 [n = 4 patients], 1.0 mg/m2 [n = 9 patients], or 1.3 mg/m2 [n = 7 patients]) administered on Days 1 and 4 of each cycle. Results: The maximum tolerated dose of bortezomib with R-CHOP was not reached, and the 1.3-mg/m 2 dose level had acceptable tolerability. A dose-limiting toxicity (pulmonary) was only observed in 1 patient receiving 1.0 mg/m2 of bortezomib. Neuropathy occurred in 13 patients (65%), but was mostly grade 1 (45%) and reached grade 3 in only 1 patient (all toxicities were graded using the Common Terminology Criteria for Adverse Events, version 3.0). Grade 4 hematologic toxicity occurred in 7 patients (35%). Of 19 evaluable patients, all responded, with 18 (95%) cases of complete response/complete response unconfirmed achieved and 1 (5%) partial response reported. At a median follow-up of 56 months, overall survival at 4 years was 75% and progression-free survival was 58%. Conclusions: Bortezomib at a dose of 1.3 mg/m2 twice per cycle can be added to R-CHOP chemotherapy with acceptable toxicity. Multi-institutional and cooperative group follow-up studies of this regimen are currently ongoing. Cancer 2010.

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