A phase I/II study of bortezomib plus CHOP every 2 weeks (CHOP-14) in patients with advanced-stage diffuse large B-cell lymphomas.
- Author:
Jeong Eun KIM
1
;
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
Author Information
- Publication Type:Original Article
- Keywords: Bortezomib; CHOP-14; Diffuse large B-cell lymphoma
- MeSH: 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
- From:Korean Journal of Hematology 2012;47(1):53-59
- CountryRepublic of Korea
- Language:English
- 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.
