TY - JOUR
T1 - Phase I-II trial of bortezomib plus oral cyclophosphamide and prednisone in relapsed and refractory multiple myeloma
AU - Reece, Donna E.
AU - Rodriguez, Giovanni Piza
AU - Chen, Christine
AU - Trudel, Suzanne
AU - Kukreti, Vishal
AU - Mikhael, Joseph
AU - Pantoja, Mariela
AU - Xu, Wei
AU - Stewart, A. Keith
PY - 2008/10/10
Y1 - 2008/10/10
N2 - 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/m2 on days 1, 4, 8, and 11 and 1.5 mg/m2 on days 1, 8, and 15, each on a 28-day cycle) could be safely given with cyclophosphamide 300 mg/m2 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/m2 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.
AB - 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/m2 on days 1, 4, 8, and 11 and 1.5 mg/m2 on days 1, 8, and 15, each on a 28-day cycle) could be safely given with cyclophosphamide 300 mg/m2 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/m2 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.
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U2 - 10.1200/JCO.2007.14.2372
DO - 10.1200/JCO.2007.14.2372
M3 - Article
C2 - 18645194
AN - SCOPUS:54249122860
SN - 0732-183X
VL - 26
SP - 4777
EP - 4783
JO - Journal of Clinical Oncology
JF - Journal of Clinical Oncology
IS - 29
ER -