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 Kim, Dok Hyun Yoon, Geundoo Jang, Dae Ho Lee, Shin Kim, Chan Sik Park, Jooryung Huh, Won Seog Kim, Jinny Park, Jae Hoon Lee, Soon Il Lee, Cheolwon Suh

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9 Scopus citations

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/m 2 bortezomib administration on day 1 and 4 in addition to the CHOP-14regimen 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/m 2. 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.

Original languageEnglish (US)
Pages (from-to)53-59
Number of pages7
JournalKorean Journal of Hematology
Volume47
Issue number1
DOIs
StatePublished - Mar 2012

Keywords

  • Bortezomib
  • Chop-14
  • Diffuse large b-cell lymphoma

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    Kim, J. E., Yoon, D. H., Jang, G., Lee, D. H., Kim, S., Park, C. S., Huh, J., Kim, W. S., Park, J., Lee, J. H., Lee, S. I., & Suh, C. (2012). 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, 47(1), 53-59. https://doi.org/10.5045/kjh.2012.47.1.53