Korean J Hematol.  2012 Mar;47(1):53-59. 10.5045/kjh.2012.47.1.53.

A phase I/II study of bortezomib plus CHOP every 2 weeks (CHOP-14) in patients with advanced-stage diffuse large B-cell lymphomas

Affiliations
  • 1Department of Oncology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea. csuh@amc.seoul.kr
  • 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.

Abstract

BACKGROUND
Bortezomib targets molecular dysregulation of nuclear factor-kappaB 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 microg/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.

Keyword

Bortezomib; CHOP-14; Diffuse large B-cell lymphoma

MeSH Terms

Appointments and Schedules
B-Lymphocytes
Boronic Acids
Cell Cycle Checkpoints
Cohort Studies
Cyclophosphamide
Doxorubicin
Granulocyte Colony-Stimulating Factor
Humans
Lymphoma, B-Cell
Maximum Tolerated Dose
Prednisone
Pyrazines
Recombinant Proteins
Vincristine
Bortezomib
Boronic Acids
Cyclophosphamide
Doxorubicin
Granulocyte Colony-Stimulating Factor
Prednisone
Pyrazines
Recombinant Proteins
Vincristine

Figure

  • Fig. 1 Profile of the phase I and phase II trials.

  • Fig. 2 (A) Event-free survival (EFS) and (B) overall survival (OS) of patients in the phase II study.


Cited by  1 articles

Review of the clinical research conducted by the Consortium for Improving Survival of Lymphoma of the Korean Society of Hematology Lymphoma Working Party
Cheolwon Suh, Won Seog Kim, Jin Seok Kim, Byeong-Bae Park
Blood Res. 2013;48(3):171-177.    doi: 10.5045/br.2013.48.3.171.


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