TY - JOUR
T1 - Phase I trial of first-line bortezomib/thalidomide plus chemotherapy for induction and stem cell mobilization in patients with multiple myeloma
AU - Badros, Ashraf
AU - Goloubeva, Olga
AU - Fenton, Robert
AU - Rapoport, Aaron P.
AU - Akpek, Gorgun
AU - Harris, Carolynn
AU - Ruehle, Kathleen
AU - Westphal, Sandra
AU - Meisenberg, Barry
N1 - Funding Information:
This work was supported in part by Millennium Pharmaceuticals, Inc.
PY - 2006/11
Y1 - 2006/11
N2 - Background: In preclinical studies, bortezomib was shown to suppress tumor growth, sensitize malignant cells to apoptosis, and reverse chemotherapy resistance. Patients and Methods: We evaluated the addition of escalating doses of bortezomib 0.7, 1, and 1.3 mg/mg2 intravenously on days 1, 4, and 8 to DT-PACE (cisplatin 10 mg/m2, doxorubicin 10 mg/m2, cyclophosphamide 400 mg/m2, and etoposide 40 mg/m2 per day by intravenous continuous infusion on days 1-4) plus oral dexamethasone 40 mg on days 1-4 and thalidomide 200 mg on days 1-8 in newly diagnosed patients with multiple myeloma. Peripheral blood stem cells were collected after cycle 1. Twelve patients completed the study, and all received autologous stem cell transplantation (SCT). Results: Hematologic toxicities were predictable, with 3 episodes of neutropenic fever. Grade ≥ 2 nonhematologic toxicities included diarrhea (n = 1), deep vein thrombosis (n = 2), hypotension (n = 2), syncope (n = 1), and peripheral neuropathy (n = 3). The median number of CD34+ cells collected was 20.57 × 106 CD34+ cells/kg. After 2 cycles, 10 of 12 patients exhibited a partial response or better. Best response after autologous SGT, complete response/near complete response was exhibited in 9 patients, and partial response was exhibited in 3 patients. At a median of 20 months, 4 patients experienced relapse and 1 had died. Bortezomib/DT-PACE compared favorably with DT-PAGE with regard to leukapheresis days, total GD34+ cell collection, and engraftment. Conclusion: This novel strategy of simultaneous proteasome inhibition in combination with thalidomide and chemotherapy was effective and safe, allowing for adequate stem cell collection and early autologous SCT; its impact on overall survival, especially in patients with high-risk myeloma, awaits further investigation.
AB - Background: In preclinical studies, bortezomib was shown to suppress tumor growth, sensitize malignant cells to apoptosis, and reverse chemotherapy resistance. Patients and Methods: We evaluated the addition of escalating doses of bortezomib 0.7, 1, and 1.3 mg/mg2 intravenously on days 1, 4, and 8 to DT-PACE (cisplatin 10 mg/m2, doxorubicin 10 mg/m2, cyclophosphamide 400 mg/m2, and etoposide 40 mg/m2 per day by intravenous continuous infusion on days 1-4) plus oral dexamethasone 40 mg on days 1-4 and thalidomide 200 mg on days 1-8 in newly diagnosed patients with multiple myeloma. Peripheral blood stem cells were collected after cycle 1. Twelve patients completed the study, and all received autologous stem cell transplantation (SCT). Results: Hematologic toxicities were predictable, with 3 episodes of neutropenic fever. Grade ≥ 2 nonhematologic toxicities included diarrhea (n = 1), deep vein thrombosis (n = 2), hypotension (n = 2), syncope (n = 1), and peripheral neuropathy (n = 3). The median number of CD34+ cells collected was 20.57 × 106 CD34+ cells/kg. After 2 cycles, 10 of 12 patients exhibited a partial response or better. Best response after autologous SGT, complete response/near complete response was exhibited in 9 patients, and partial response was exhibited in 3 patients. At a median of 20 months, 4 patients experienced relapse and 1 had died. Bortezomib/DT-PACE compared favorably with DT-PAGE with regard to leukapheresis days, total GD34+ cell collection, and engraftment. Conclusion: This novel strategy of simultaneous proteasome inhibition in combination with thalidomide and chemotherapy was effective and safe, allowing for adequate stem cell collection and early autologous SCT; its impact on overall survival, especially in patients with high-risk myeloma, awaits further investigation.
KW - Cisplatin
KW - Cyclophosphamide
KW - Doxorubicin
KW - Engraftment
UR - http://www.scopus.com/inward/record.url?scp=34248218687&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=34248218687&partnerID=8YFLogxK
U2 - 10.3816/CLM.2006.n.061
DO - 10.3816/CLM.2006.n.061
M3 - Article
C2 - 17229337
AN - SCOPUS:34248218687
SN - 1557-9190
VL - 7
SP - 210
EP - 216
JO - Clinical Lymphoma and Myeloma
JF - Clinical Lymphoma and Myeloma
IS - 3
ER -