A randomized phase II, open-label and multicenter study of combination regimens of bortezomib at two doses by subcutaneous injection for newly diagnosed multiple myeloma patients.

Abstract

PURPOSE:

Combinations of bortezomib (Velcade), cyclophosphamide and dexamethasone have shown significant efficacy and safety for patients of newly diagnosed multiple myeloma (NDMM). In this study, we compared the efficacy and safety of modified VCD regimens with novel changes in bortezomib dose and schedule for NDMM.

METHODS:

Eighty-five NDMM patients from multiple centers were randomly assigned to a high-dose (1.6 mg/m2) (group A) or a low-dose (1.3 mg/m2) (group B) bortezomib, administrated on days 1, 6, 11, and 16 subcutaneously in a 4-week cycle for nine cycles, combined with 40 mg dexamethasone on bortezomib days and cyclophosphamide 300 mg/m2 on days 1-3 intravenously.

RESULTS:

After four cycles, complete response (CR) or better in group A (43.6%) was higher than that in group B (12.8%) (P = 0.002). During induction, for patients with R-ISS stage III, the CR or better rate in group A was superior to that in group B (P = 0.01). Of patients < 65, the CR or better rate of group A was superior to that of group B (P = 0.004). Rapid onset of CR occurred in group A (P < 0.01). Meanwhile, rate of 3-4 diarrhea was higher in group A (P = 0.03), which caused higher rate of dose reduction for patients ≥ 65 (P = 0.041). No significant difference between the two groups in PFS and OS.

CONCLUSIONS:

The studied high-dose VCD as induction regimen had an improved CR rate, especially in patients < 65 or with R-ISS stage III, and is feasible for young and high-risk patients. Trial registration ClinicalTrials.gov: NCT02086942.

• Authors: Feng Li, Fu-Sheng Yao, Xi-Jun Zhu, Wei-Ying Gu, Xiao-Hua Wang, Bing Chen, Dong-Ping Huang, Jia-Hua Ding, Tian-Qin Wu, Yan Zhu, Qian Zhao, Yu-Mei Tang, Ping Song, Xiao-Gang Zhou, Zhi-Ming An, Xing Guo, Xu-Li Wang, Long Zhong, Xiao-Bao Xie, Yong-Ping Zhai
• Journal: Journal of cancer research and clinical oncology (J Cancer Res Clin Oncol) Vol. 145 Issue 9 Pg. 2343-2355 (Sep 2019) ISSN: 1432-1335 [Electronic] Germany
• PMID: 31280348 (Publication Type: Clinical Trial, Phase II, Journal Article, Multicenter Study, Randomized Controlled Trial)

Chemical References

• Bortezomib
• Dexamethasone
• Cyclophosphamide
• Teniposide

Topics

• Adult
• Aged
• Aged, 80 and over
• Antineoplastic Combined Chemotherapy Protocols (administration & dosage)
• Bortezomib (administration & dosage, adverse effects)
• Cyclophosphamide (administration & dosage, adverse effects)
• Dexamethasone (administration & dosage, adverse effects)
• Dose-Response Relationship, Drug
• Drug Administration Schedule
• Female
• Humans
• Injections, Subcutaneous
• Male
• Middle Aged
• Multiple Myeloma (diagnosis, drug therapy)
• Teniposide (administration & dosage)
• Treatment Outcome