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

• Kim JE
• Yoon DH
• Jang G
• Lee DH
• Kim S
• Park CS
• Huh J
• Kim WS
• Park J
• Lee JH
• Lee SI
• Suh C

• KMID: 2251971
• DOI: http://doi.org/10.5045/kjh.2012.47.1.53

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

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

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

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