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Korean J Hematol 2012; 47(1):
Published online March 31, 2012
https://doi.org/10.5045/kjh.2012.47.1.53
© The Korean Society of Hematology
A phase I/II study of bortezomib plus CHOP every 2 weeks (CHOP-14) in patients with advanced-stage diffuse large B-cell lymphomas
1Department of Oncology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea.
2Department of Pathology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea.
3Department of Internal Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.
4Department of Internal Medicine, Gachon Medical School, Incheon, Korea.
5Department of Internal Medicine, Dankook University College of Medicine, Cheonan, Korea.
Correspondence to : Correspondence to Cheolwon Suh, M.D., Ph.D. Department of Oncology, Asan Medical Center, University of Ulsan College of Medicine, 88, Olympic-ro 43-gil, Songpa-gu, Seoul 138-736, Korea. Tel: +82-2-3010-3209, Fax: +82-2-3010-6961, csuh@amc.seoul.kr
This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/3.0/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
Background
Bortezomib targets molecular dysregulation of nuclear factor-κB activation and cell cycle control, which are characteristic features of diffuse large B-cell lymphoma (DLBCL). We evaluated the safety and efficacy of bortezomib treatment with dose-dense cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) every 2 weeks (CHOP-14).
Methods
Untreated DLBCL patients were enrolled. A phase I dose-escalation study with 1.0, 1.3, and 1.6 mg/m2 bortezomib administration on day 1 and 4 in addition to the CHOP-14 regimen was performed to determine the maximum tolerated dose (MTD) and the dose-limiting toxicity (DLT). Lenograstim 5 µg/kg/d was administered on day 4-13. The bortezomib dose from the phase I study was used in the phase II study.
Results
Nine and 37 patients were enrolled in the phase I and phase II studies, respectively. The analysis of the phase II results (40 patients) included data of the 3 patients in the last MTD dose cohort of the phase I trial. During the phase I trial, no DLT was observed at any bortezomib dose; therefore, the recommended dose was 1.6 mg/m2. In phase II, the overall response rate was 95% (complete response: 80%; partial response: 15%). Nine out of the 40 patients showed grade 3 sensory neuropathy, and 22 required at least 1 dose reduction. Three patients could not complete the intended 6 cycles of treatment because of severe neuropathy.
Conclusion
Bortezomib plus CHOP-14 was highly effective for the treatment of untreated DLBCL patients, but in many cases, dose or schedule modification was required to reduce neurotoxicity.
Keywords Bortezomib, CHOP-14, Diffuse large B-cell lymphoma
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Original Article
Korean J Hematol 2012; 47(1): 53-59
Published online March 31, 2012 https://doi.org/10.5045/kjh.2012.47.1.53
Copyright © The Korean Society of Hematology.
A phase I/II study of bortezomib plus CHOP every 2 weeks (CHOP-14) in patients with advanced-stage diffuse large B-cell lymphomas
Jeong Eun Kim1, Dok Hyun Yoon1, Geundoo Jang1, Dae Ho Lee1, Shin Kim1, Chan-Sik Park2, Jooryung Huh2, Won Seog Kim3, Jinny Park4, Jae Hoon Lee4, Soon Il Lee5, and Cheolwon Suh1*
1Department of Oncology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea.
2Department of Pathology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea.
3Department of Internal Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.
4Department of Internal Medicine, Gachon Medical School, Incheon, Korea.
5Department of Internal Medicine, Dankook University College of Medicine, Cheonan, Korea.
Correspondence to: Correspondence to Cheolwon Suh, M.D., Ph.D. Department of Oncology, Asan Medical Center, University of Ulsan College of Medicine, 88, Olympic-ro 43-gil, Songpa-gu, Seoul 138-736, Korea. Tel: +82-2-3010-3209, Fax: +82-2-3010-6961, csuh@amc.seoul.kr
This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/3.0/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
Abstract
Background
Bortezomib targets molecular dysregulation of nuclear factor-κB activation and cell cycle control, which are characteristic features of diffuse large B-cell lymphoma (DLBCL). We evaluated the safety and efficacy of bortezomib treatment with dose-dense cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) every 2 weeks (CHOP-14).
Methods
Untreated DLBCL patients were enrolled. A phase I dose-escalation study with 1.0, 1.3, and 1.6 mg/m2 bortezomib administration on day 1 and 4 in addition to the CHOP-14 regimen was performed to determine the maximum tolerated dose (MTD) and the dose-limiting toxicity (DLT). Lenograstim 5 µg/kg/d was administered on day 4-13. The bortezomib dose from the phase I study was used in the phase II study.
Results
Nine and 37 patients were enrolled in the phase I and phase II studies, respectively. The analysis of the phase II results (40 patients) included data of the 3 patients in the last MTD dose cohort of the phase I trial. During the phase I trial, no DLT was observed at any bortezomib dose; therefore, the recommended dose was 1.6 mg/m2. In phase II, the overall response rate was 95% (complete response: 80%; partial response: 15%). Nine out of the 40 patients showed grade 3 sensory neuropathy, and 22 required at least 1 dose reduction. Three patients could not complete the intended 6 cycles of treatment because of severe neuropathy.
Conclusion
Bortezomib plus CHOP-14 was highly effective for the treatment of untreated DLBCL patients, but in many cases, dose or schedule modification was required to reduce neurotoxicity.
Keywords: Bortezomib, CHOP-14, Diffuse large B-cell lymphoma
Fig 1.
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Profile of the phase I and phase II trials.
Fig 2.
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Table 1 . Baseline characteristics of the patients (N=49)..
Abbreviations: IPI, international prognostic index; ECOG, Eastern Cooperative Oncology Group..
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Table 2 . Adverse events after bortezomib plus CHOP-14 treatment (N=49)..
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Table 3 . Response after bortezomib plus CHOP-14 treatment..
Abbreviations: CR, complete response; PR, partial response; SD, stable disease; PD, progressive disease..
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