PURPOSE: 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. PATIENTS AND 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. CONCLUSION: 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.
PURPOSE: 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. PATIENTS AND 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. CONCLUSION: 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: Mridul Agrawal; Jennifer Kanakry; Christina A Arnold; Daniel L Suzman; Luckson Mathieu; Yvette L Kasamon; Douglas E Gladstone; Richard F Ambinder; Nilanjan Ghosh Journal: Ann Hematol Date: 2014-07 Impact factor: 3.673
Authors: Mei Lan Tan; Jer Ping Ooi; Nawfal Ismail; Ahmed Ismail Hassan Moad; Tengku Sifzizul Tengku Muhammad Journal: Pharm Res Date: 2009-04-30 Impact factor: 4.200
Authors: C B Reeder; D E Reece; V Kukreti; C Chen; S Trudel; J Hentz; B Noble; N A Pirooz; J E Spong; J G Piza; V H J Zepeda; J R Mikhael; J F Leis; P L Bergsagel; R Fonseca; A K Stewart Journal: Leukemia Date: 2009-02-19 Impact factor: 11.528