A phase I/II study of bortezomib plus CHOP every 2 weeks (CHOP-14) in patients with advanced-stage diffuse large B-cell lymphomas
Korean Journal of Hematology
; : 53-59, 2012.
Article
in En
| WPRIM
| ID: wpr-720217
Responsible library:
WPRO
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.
Key words
Full text:
1
Database:
WPRIM
Main subject:
Appointments and Schedules
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Pyrazines
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Vincristine
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Boronic Acids
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Recombinant Proteins
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Prednisone
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B-Lymphocytes
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Doxorubicin
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Cohort Studies
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Granulocyte Colony-Stimulating Factor
Type of study:
Etiology_studies
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Incidence_studies
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Observational_studies
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Risk_factors_studies
Limits:
Humans
Language:
En
Journal:
Korean Journal of Hematology
Year:
2012
Document type:
Article