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KMID : 0366220120470010053
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Korean Journal of Hematology
2012 Volume.47 No. 1 p.53 ~ p.59
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A phase I/II study of bortezomib plus CHOP every 2 weeks (CHOP-14) in patients with advanced-stage diffuse large B-cell lymphomas
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Kim Jeong-Eun
Yoon Dok-Hyun
Jang Geun-Doo
Lee Dae-Ho
Kim Shin
Park Chan-Sik
Huh Joo-Ryung
Kim Won-Seog
Park Jinny
Lee Jae-Hoon
Lee Soon-Il
Suh Cheol-Won
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Abstract
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Background: Bortezomib targets molecular dysregulation of nuclear factor-kB 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 mg/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.
Conslusion: 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.
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KEYWORD
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Bortezomib, CHOP-14, Diffuse large B-cell lymphoma
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