Phase I dose-escalation study of cyclophosphamide combined with bortezomib and dexamethasone in Japanese patients with relapsed and/or refractory multiple myeloma

Int J Hematol. 2015 Oct;102(4):434-40. doi: 10.1007/s12185-015-1846-5. Epub 2015 Aug 23.

Abstract

The present study was conducted to determine the recommended dose (RD) of cyclophosphamide (CPM) in the CBD regimen, a triplet combination of CPM, bortezomib (BTZ), and dexamethasone (Dex), for relapsed and/or refractory multiple myeloma (RRMM). Patients received intravenous CPM on days 1 and 8 at one of three dose levels: 300, 400, or 500 mg/m(2), with dose escalation in a 3 + 3 design. BTZ at 1.3 mg/m(2) was given twice weekly in 3-week cycles, with Dex at 20 mg/m(2) on the day of and day after BTZ. Of 16 patients enrolled, 15 eligible patients were allocated to the study. Dose-limiting toxicities (DLTs) were seen in two patients: one in dose level 1 with increased γ-GTP and the other in dose level 3 with increased γ-GTP and ALT. Both patients spontaneously recovered from DLT. Neither therapy-related mortality nor severe adverse events were reported during the study. Therefore, the RD of CPM was determined as 500 mg/m(2). Overall, 2 (13.3 %), 1 (6.7 %), and 8 (53.3 %) patients achieved CR, VGPR, and PR, respectively. The regimen was well tolerated and showed promising activity in patients with RRMM.

Keywords: CBD regimen; Cyclophosphamide; Multiple myeloma; Recommended dose.

Publication types

  • Clinical Trial, Phase I
  • Multicenter Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Antineoplastic Combined Chemotherapy Protocols / administration & dosage*
  • Antineoplastic Combined Chemotherapy Protocols / adverse effects
  • Bortezomib / administration & dosage
  • Bortezomib / adverse effects
  • Cyclophosphamide / administration & dosage
  • Cyclophosphamide / adverse effects
  • Dexamethasone / administration & dosage
  • Dexamethasone / adverse effects
  • Female
  • Humans
  • Male
  • Middle Aged
  • Multiple Myeloma / drug therapy*

Substances

  • Bortezomib
  • Dexamethasone
  • Cyclophosphamide