title: Phase I-II trial of bortezomib plus oral cyclophosphamide and prednisone in relapsed and refractory multiple myeloma.
abstract: OBJECTIVE
  The combination of oral weekly cyclophosphamide and alternate day prednisone is a convenient regimen for relapsed/refractory multiple myeloma (MM), and we sought to improve its efficacy by adding bortezomib, a proteasome inhibitor with proven antimyeloma activity.
  
  
  METHODS
  We conducted a phase I-II trial evaluating six dose levels to define the maximum tolerated dose (MTD) of this combination in relapsed/refractory MM. An additional 10 patients were evaluated at the highest dose level reached.
  
  
  RESULTS
  Thirty-seven patients were treated on this study. The MTD was not defined. Both of the highest dose levels of bortezomib tested (1.3 mg/m(2) on days 1, 4, 8, and 11 and 1.5 mg/m(2) on days 1, 8, and 15, each on a 28-day cycle) could be safely given with cyclophosphamide 300 mg/m(2) per week and prednisone. At these dose levels, the overall response rate was 95% (complete responses [CR] plus partial response plus minimal response), with CR observed in more than 50% of patients. The weekly bortezomib regimen resulted in fewer instances of grade 3 thrombocytopenia and grade 1 to 2 peripheral neuropathy; the 1-year progression-free and overall survival probabilities with this dose level were 83% (95% CI, 73% to 96%) and 100%, respectively.
  
  
  CONCLUSIONS
  Weekly bortezomib 1.5 mg/m(2) plus oral cyclophosphamide and prednisone produces an unprecedented response rate and encouraging 1-year survival in relapsed/refractory patients with MM. Further evaluation of this promising regimen is warranted both in relapsed and newly diagnosed disease.
authors.affiliation: Department of Medical Oncology and Hematology, Princess Margaret Hospital, 610 University Ave, Suite 5-207, Toronto, Ontario, M5G 2M9 Canada. donna.reece@uhn.on.ca
authors.forename: Donna E
authors.initials: DE
authors.lastname: Reece
authors.forename: Giovanni Piza
authors.initials: GP
authors.lastname: Rodriguez
authors.forename: Christine
authors.initials: C
authors.lastname: Chen
authors.forename: Suzanne
authors.initials: S
authors.lastname: Trudel
authors.forename: Vishal
authors.initials: V
authors.lastname: Kukreti
authors.forename: Joseph
authors.initials: J
authors.lastname: Mikhael
authors.forename: Mariela
authors.initials: M
authors.lastname: Pantoja
authors.forename: Wei
authors.initials: W
authors.lastname: Xu
authors.forename: A Keith
authors.initials: AK
authors.lastname: Stewart
mesh_terms: D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000008:administration & dosage*; D001897:Boronic Acids / Q000008:administration & dosage*; D000069286:Bortezomib; D003520:Cyclophosphamide / Q000008:administration & dosage*; D005260:Female; D005938:Glucocorticoids / Q000008:administration & dosage; D006801:Humans; D008297:Male; D008875:Middle Aged; D009101:Multiple Myeloma / Q000188:drug therapy*; D011241:Prednisone / Q000008:administration & dosage; D011719:Pyrazines / Q000008:administration & dosage*; D016019:Survival Analysis
chemical_list: D000970:Antineoplastic Agents; D001897:Boronic Acids; D005938:Glucocorticoids; D011719:Pyrazines; D000069286:Bortezomib; D003520:Cyclophosphamide; D011241:Prednisone