title: An open-label phase I/II study of cyclophosphamide, bortezomib, pegylated liposomal doxorubicin, and dexamethasone in newly diagnosed myeloma.
abstract: We conducted a phase 1/2 trial evaluating the combination of cyclophosphamide, bortezomib, pegylated liposomal doxorubicin, and dexamethasone (CVDD) for newly diagnosed multiple myeloma (MM). The primary objective of the phase 1 was to evaluate the safety and tolerability of maximum planned dose (MPD) and the phase 2 was to assess the overall response rate. Patients received 6-8 cycles of CVDD at four dose levels. There were no dose-limiting toxicities. The MPD was cyclophosphamide 750 mg/m(2) IV on day 1, bortezomib 1.3 mg/m(2) IV on days 1, 4, 8, 11, pegylated liposomal doxorubicin 30 mg/m(2) IV on day 4, and dexamethasone 20 mg orally on the day of and after bortezomib (21-d cycle). Forty-nine patients were treated at the MPD of which 22% had high-risk myeloma. The most common grade ≥3 toxicities included myelosuppression, infection, and fatigue. Overall response and complete response rates were 91% and 26% in standard-risk, and 100% and 58% in high-risk cohort, respectively. After a median follow-up of 34 months, the median progression-free survival was 31.3 months. The 2-yr overall survival was 91.1% in the standard-risk and 88.9% in the high-risk cohort, respectively. CVDD regimen was well tolerated and was highly active in newly diagnosed MM.
authors.affiliation: Department of Blood and Marrow Transplantation, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL, USA.|Chemical Biology and Molecular Medicine Program, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL, USA.
authors.forename: Taiga
authors.initials: T
authors.lastname: Nishihori
authors.affiliation: Chemical Biology and Molecular Medicine Program, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL, USA.|Department of Malignant Hematology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL, USA.
authors.forename: Rachid
authors.initials: R
authors.lastname: Baz
authors.affiliation: Chemical Biology and Molecular Medicine Program, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL, USA.|Department of Malignant Hematology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL, USA.
authors.forename: Kenneth
authors.initials: K
authors.lastname: Shain
authors.affiliation: Chemical Biology and Molecular Medicine Program, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL, USA.|Biostatistics core, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL, USA.
authors.forename: Jongphil
authors.initials: J
authors.lastname: Kim
authors.affiliation: Department of Blood and Marrow Transplantation, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL, USA.|Chemical Biology and Molecular Medicine Program, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL, USA.
authors.forename: Jose L
authors.initials: JL
authors.lastname: Ochoa-Bayona
authors.affiliation: Biostatistics core, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL, USA.
authors.forename: Binglin
authors.initials: B
authors.lastname: Yue
authors.affiliation: Department of Blood and Marrow Transplantation, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL, USA.|Chemical Biology and Molecular Medicine Program, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL, USA.
authors.forename: Daniel
authors.initials: D
authors.lastname: Sullivan
authors.affiliation: Chemical Biology and Molecular Medicine Program, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL, USA.|Department of Malignant Hematology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL, USA.
authors.forename: William
authors.initials: W
authors.lastname: Dalton
authors.affiliation: Department of Blood and Marrow Transplantation, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL, USA.|Chemical Biology and Molecular Medicine Program, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL, USA.
authors.forename: Melissa
authors.initials: M
authors.lastname: Alsina
mesh_terms: D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage* / Q000009:adverse effects; D000069286:Bortezomib / Q000008:administration & dosage / Q000009:adverse effects; D003520:Cyclophosphamide / Q000008:administration & dosage / Q000009:adverse effects; D003907:Dexamethasone / Q000008:administration & dosage / Q000009:adverse effects; D018572:Disease-Free Survival; D004317:Doxorubicin / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009101:Multiple Myeloma / Q000188:drug therapy* / Q000401:mortality*; D011092:Polyethylene Glycols / Q000008:administration & dosage / Q000009:adverse effects; D015996:Survival Rate
chemical_list: C506643:liposomal doxorubicin; D011092:Polyethylene Glycols; D000069286:Bortezomib; D003907:Dexamethasone; D004317:Doxorubicin; D003520:Cyclophosphamide
keywords: bortezomib; cyclophosphamide; multiple myeloma; pegylated liposomal doxorubicin