title: Community-Based Phase IIIB Trial of Three UPFRONT Bortezomib-Based Myeloma Regimens.
abstract: OBJECTIVE
  The US community-based, phase IIIB UPFRONT trial was designed to compare three frontline bortezomib-based regimens in transplantation-ineligible patients with myeloma.
  
  
  METHODS
  Patients (N = 502) were randomly assigned 1:1:1 to 24 weeks (eight 21-day cycles) of induction with bortezomib-dexamethasone (VD; n = 168; intravenous bortezomib 1.3 mg/m(2), days 1, 4, 8, and 11 plus oral dexamethasone 20 mg, days 1, 2, 4, 5, 8, 9, 11, and 12 [cycles 1 to 4], or 1, 2, 4, and 5 [cycles 5 to 8]), bortezomib-thalidomide-dexamethasone (VTD; n = 167; bortezomib and dexamethasone as before plus oral thalidomide 100 mg, days 1 to 21), or bortezomib-melphalan-prednisone (VMP; n = 167; bortezomib as before plus oral melphalan 9 mg/m(2) and oral prednisone 60 mg/m(2), days 1 to 4, every other cycle), followed by 25 weeks (five 35-day cycles) of bortezomib maintenance (1.6 mg/m(2), days 1, 8, 15, and 22). The primary end point was progression-free survival.
  
  
  RESULTS
  After 42.7 months' median follow-up, median progression-free survival with VD, VTD, and VMP was 14.7, 15.4, and 17.3 months, respectively; median overall survival was 49.8, 51.5, and 53.1 months, with no significant differences among treatments for either end point (global P = .46 and P = .79, respectively, Wald test). Overall response rates were 73% (VD), 80% (VTD), and 70% (VMP). Adverse events were more common with VTD than VD or VMP. Bortezomib maintenance was feasible without producing cumulative toxicity.
  
  
  CONCLUSIONS
  Although all bortezomib-containing regimens produced good outcomes, VTD and VMP did not appear to offer an advantage over VD in transplantation-ineligible patients with myeloma treated in US community practice.
authors.affiliation: Ruben Niesvizky, Weill Cornell Medical College, New York Presbyterian Hospital, New York, NY; Ian W. Flinn, Sarah Cannon Research Institute and Tennessee Oncology, Nashville, TN; Robert Rifkin, US Oncology Research/McKesson Specialty Health, The Woodlands, TX; Nashat Gabrail, Gabrail Cancer Center, Canton, OH; Veena Charu, Pacific Cancer Medical Center, Anaheim, CA; Billy Clowney, Santee Hematology/Oncology, Sumter, SC; James Essell, Sarah Cannon Research Institute and Oncology Hematology Care, Cincinnati, OH; Yousuf Gaffar, University of Maryland-St Joseph Medical Center, Towson, MD; Thomas Warr, Clinic Cancer Care, Great Falls, MT; Rachel Neuwirth, Yanyan Zhu, Jennifer Elliott, Dixie-Lee Esseltine, and Liviu Niculescu, Millennium Pharmaceuticals, Cambridge, MA; and James Reeves, Sarah Cannon Research Institute and Florida Cancer Specialists, Fort Myers, FL. run9001@med.cornell.edu.
authors.forename: Ruben
authors.initials: R
authors.lastname: Niesvizky
authors.affiliation: Ruben Niesvizky, Weill Cornell Medical College, New York Presbyterian Hospital, New York, NY; Ian W. Flinn, Sarah Cannon Research Institute and Tennessee Oncology, Nashville, TN; Robert Rifkin, US Oncology Research/McKesson Specialty Health, The Woodlands, TX; Nashat Gabrail, Gabrail Cancer Center, Canton, OH; Veena Charu, Pacific Cancer Medical Center, Anaheim, CA; Billy Clowney, Santee Hematology/Oncology, Sumter, SC; James Essell, Sarah Cannon Research Institute and Oncology Hematology Care, Cincinnati, OH; Yousuf Gaffar, University of Maryland-St Joseph Medical Center, Towson, MD; Thomas Warr, Clinic Cancer Care, Great Falls, MT; Rachel Neuwirth, Yanyan Zhu, Jennifer Elliott, Dixie-Lee Esseltine, and Liviu Niculescu, Millennium Pharmaceuticals, Cambridge, MA; and James Reeves, Sarah Cannon Research Institute and Florida Cancer Specialists, Fort Myers, FL.
authors.forename: Ian W
authors.initials: IW
authors.lastname: Flinn
authors.affiliation: Ruben Niesvizky, Weill Cornell Medical College, New York Presbyterian Hospital, New York, NY; Ian W. Flinn, Sarah Cannon Research Institute and Tennessee Oncology, Nashville, TN; Robert Rifkin, US Oncology Research/McKesson Specialty Health, The Woodlands, TX; Nashat Gabrail, Gabrail Cancer Center, Canton, OH; Veena Charu, Pacific Cancer Medical Center, Anaheim, CA; Billy Clowney, Santee Hematology/Oncology, Sumter, SC; James Essell, Sarah Cannon Research Institute and Oncology Hematology Care, Cincinnati, OH; Yousuf Gaffar, University of Maryland-St Joseph Medical Center, Towson, MD; Thomas Warr, Clinic Cancer Care, Great Falls, MT; Rachel Neuwirth, Yanyan Zhu, Jennifer Elliott, Dixie-Lee Esseltine, and Liviu Niculescu, Millennium Pharmaceuticals, Cambridge, MA; and James Reeves, Sarah Cannon Research Institute and Florida Cancer Specialists, Fort Myers, FL.
authors.forename: Robert
authors.initials: R
authors.lastname: Rifkin
authors.affiliation: Ruben Niesvizky, Weill Cornell Medical College, New York Presbyterian Hospital, New York, NY; Ian W. Flinn, Sarah Cannon Research Institute and Tennessee Oncology, Nashville, TN; Robert Rifkin, US Oncology Research/McKesson Specialty Health, The Woodlands, TX; Nashat Gabrail, Gabrail Cancer Center, Canton, OH; Veena Charu, Pacific Cancer Medical Center, Anaheim, CA; Billy Clowney, Santee Hematology/Oncology, Sumter, SC; James Essell, Sarah Cannon Research Institute and Oncology Hematology Care, Cincinnati, OH; Yousuf Gaffar, University of Maryland-St Joseph Medical Center, Towson, MD; Thomas Warr, Clinic Cancer Care, Great Falls, MT; Rachel Neuwirth, Yanyan Zhu, Jennifer Elliott, Dixie-Lee Esseltine, and Liviu Niculescu, Millennium Pharmaceuticals, Cambridge, MA; and James Reeves, Sarah Cannon Research Institute and Florida Cancer Specialists, Fort Myers, FL.
authors.forename: Nashat
authors.initials: N
authors.lastname: Gabrail
authors.affiliation: Ruben Niesvizky, Weill Cornell Medical College, New York Presbyterian Hospital, New York, NY; Ian W. Flinn, Sarah Cannon Research Institute and Tennessee Oncology, Nashville, TN; Robert Rifkin, US Oncology Research/McKesson Specialty Health, The Woodlands, TX; Nashat Gabrail, Gabrail Cancer Center, Canton, OH; Veena Charu, Pacific Cancer Medical Center, Anaheim, CA; Billy Clowney, Santee Hematology/Oncology, Sumter, SC; James Essell, Sarah Cannon Research Institute and Oncology Hematology Care, Cincinnati, OH; Yousuf Gaffar, University of Maryland-St Joseph Medical Center, Towson, MD; Thomas Warr, Clinic Cancer Care, Great Falls, MT; Rachel Neuwirth, Yanyan Zhu, Jennifer Elliott, Dixie-Lee Esseltine, and Liviu Niculescu, Millennium Pharmaceuticals, Cambridge, MA; and James Reeves, Sarah Cannon Research Institute and Florida Cancer Specialists, Fort Myers, FL.
authors.forename: Veena
authors.initials: V
authors.lastname: Charu
authors.affiliation: Ruben Niesvizky, Weill Cornell Medical College, New York Presbyterian Hospital, New York, NY; Ian W. Flinn, Sarah Cannon Research Institute and Tennessee Oncology, Nashville, TN; Robert Rifkin, US Oncology Research/McKesson Specialty Health, The Woodlands, TX; Nashat Gabrail, Gabrail Cancer Center, Canton, OH; Veena Charu, Pacific Cancer Medical Center, Anaheim, CA; Billy Clowney, Santee Hematology/Oncology, Sumter, SC; James Essell, Sarah Cannon Research Institute and Oncology Hematology Care, Cincinnati, OH; Yousuf Gaffar, University of Maryland-St Joseph Medical Center, Towson, MD; Thomas Warr, Clinic Cancer Care, Great Falls, MT; Rachel Neuwirth, Yanyan Zhu, Jennifer Elliott, Dixie-Lee Esseltine, and Liviu Niculescu, Millennium Pharmaceuticals, Cambridge, MA; and James Reeves, Sarah Cannon Research Institute and Florida Cancer Specialists, Fort Myers, FL.
authors.forename: Billy
authors.initials: B
authors.lastname: Clowney
authors.affiliation: Ruben Niesvizky, Weill Cornell Medical College, New York Presbyterian Hospital, New York, NY; Ian W. Flinn, Sarah Cannon Research Institute and Tennessee Oncology, Nashville, TN; Robert Rifkin, US Oncology Research/McKesson Specialty Health, The Woodlands, TX; Nashat Gabrail, Gabrail Cancer Center, Canton, OH; Veena Charu, Pacific Cancer Medical Center, Anaheim, CA; Billy Clowney, Santee Hematology/Oncology, Sumter, SC; James Essell, Sarah Cannon Research Institute and Oncology Hematology Care, Cincinnati, OH; Yousuf Gaffar, University of Maryland-St Joseph Medical Center, Towson, MD; Thomas Warr, Clinic Cancer Care, Great Falls, MT; Rachel Neuwirth, Yanyan Zhu, Jennifer Elliott, Dixie-Lee Esseltine, and Liviu Niculescu, Millennium Pharmaceuticals, Cambridge, MA; and James Reeves, Sarah Cannon Research Institute and Florida Cancer Specialists, Fort Myers, FL.
authors.forename: James
authors.initials: J
authors.lastname: Essell
authors.affiliation: Ruben Niesvizky, Weill Cornell Medical College, New York Presbyterian Hospital, New York, NY; Ian W. Flinn, Sarah Cannon Research Institute and Tennessee Oncology, Nashville, TN; Robert Rifkin, US Oncology Research/McKesson Specialty Health, The Woodlands, TX; Nashat Gabrail, Gabrail Cancer Center, Canton, OH; Veena Charu, Pacific Cancer Medical Center, Anaheim, CA; Billy Clowney, Santee Hematology/Oncology, Sumter, SC; James Essell, Sarah Cannon Research Institute and Oncology Hematology Care, Cincinnati, OH; Yousuf Gaffar, University of Maryland-St Joseph Medical Center, Towson, MD; Thomas Warr, Clinic Cancer Care, Great Falls, MT; Rachel Neuwirth, Yanyan Zhu, Jennifer Elliott, Dixie-Lee Esseltine, and Liviu Niculescu, Millennium Pharmaceuticals, Cambridge, MA; and James Reeves, Sarah Cannon Research Institute and Florida Cancer Specialists, Fort Myers, FL.
authors.forename: Yousuf
authors.initials: Y
authors.lastname: Gaffar
authors.affiliation: Ruben Niesvizky, Weill Cornell Medical College, New York Presbyterian Hospital, New York, NY; Ian W. Flinn, Sarah Cannon Research Institute and Tennessee Oncology, Nashville, TN; Robert Rifkin, US Oncology Research/McKesson Specialty Health, The Woodlands, TX; Nashat Gabrail, Gabrail Cancer Center, Canton, OH; Veena Charu, Pacific Cancer Medical Center, Anaheim, CA; Billy Clowney, Santee Hematology/Oncology, Sumter, SC; James Essell, Sarah Cannon Research Institute and Oncology Hematology Care, Cincinnati, OH; Yousuf Gaffar, University of Maryland-St Joseph Medical Center, Towson, MD; Thomas Warr, Clinic Cancer Care, Great Falls, MT; Rachel Neuwirth, Yanyan Zhu, Jennifer Elliott, Dixie-Lee Esseltine, and Liviu Niculescu, Millennium Pharmaceuticals, Cambridge, MA; and James Reeves, Sarah Cannon Research Institute and Florida Cancer Specialists, Fort Myers, FL.
authors.forename: Thomas
authors.initials: T
authors.lastname: Warr
authors.affiliation: Ruben Niesvizky, Weill Cornell Medical College, New York Presbyterian Hospital, New York, NY; Ian W. Flinn, Sarah Cannon Research Institute and Tennessee Oncology, Nashville, TN; Robert Rifkin, US Oncology Research/McKesson Specialty Health, The Woodlands, TX; Nashat Gabrail, Gabrail Cancer Center, Canton, OH; Veena Charu, Pacific Cancer Medical Center, Anaheim, CA; Billy Clowney, Santee Hematology/Oncology, Sumter, SC; James Essell, Sarah Cannon Research Institute and Oncology Hematology Care, Cincinnati, OH; Yousuf Gaffar, University of Maryland-St Joseph Medical Center, Towson, MD; Thomas Warr, Clinic Cancer Care, Great Falls, MT; Rachel Neuwirth, Yanyan Zhu, Jennifer Elliott, Dixie-Lee Esseltine, and Liviu Niculescu, Millennium Pharmaceuticals, Cambridge, MA; and James Reeves, Sarah Cannon Research Institute and Florida Cancer Specialists, Fort Myers, FL.
authors.forename: Rachel
authors.initials: R
authors.lastname: Neuwirth
authors.affiliation: Ruben Niesvizky, Weill Cornell Medical College, New York Presbyterian Hospital, New York, NY; Ian W. Flinn, Sarah Cannon Research Institute and Tennessee Oncology, Nashville, TN; Robert Rifkin, US Oncology Research/McKesson Specialty Health, The Woodlands, TX; Nashat Gabrail, Gabrail Cancer Center, Canton, OH; Veena Charu, Pacific Cancer Medical Center, Anaheim, CA; Billy Clowney, Santee Hematology/Oncology, Sumter, SC; James Essell, Sarah Cannon Research Institute and Oncology Hematology Care, Cincinnati, OH; Yousuf Gaffar, University of Maryland-St Joseph Medical Center, Towson, MD; Thomas Warr, Clinic Cancer Care, Great Falls, MT; Rachel Neuwirth, Yanyan Zhu, Jennifer Elliott, Dixie-Lee Esseltine, and Liviu Niculescu, Millennium Pharmaceuticals, Cambridge, MA; and James Reeves, Sarah Cannon Research Institute and Florida Cancer Specialists, Fort Myers, FL.
authors.forename: Yanyan
authors.initials: Y
authors.lastname: Zhu
authors.affiliation: Ruben Niesvizky, Weill Cornell Medical College, New York Presbyterian Hospital, New York, NY; Ian W. Flinn, Sarah Cannon Research Institute and Tennessee Oncology, Nashville, TN; Robert Rifkin, US Oncology Research/McKesson Specialty Health, The Woodlands, TX; Nashat Gabrail, Gabrail Cancer Center, Canton, OH; Veena Charu, Pacific Cancer Medical Center, Anaheim, CA; Billy Clowney, Santee Hematology/Oncology, Sumter, SC; James Essell, Sarah Cannon Research Institute and Oncology Hematology Care, Cincinnati, OH; Yousuf Gaffar, University of Maryland-St Joseph Medical Center, Towson, MD; Thomas Warr, Clinic Cancer Care, Great Falls, MT; Rachel Neuwirth, Yanyan Zhu, Jennifer Elliott, Dixie-Lee Esseltine, and Liviu Niculescu, Millennium Pharmaceuticals, Cambridge, MA; and James Reeves, Sarah Cannon Research Institute and Florida Cancer Specialists, Fort Myers, FL.
authors.forename: Jennifer
authors.initials: J
authors.lastname: Elliott
authors.affiliation: Ruben Niesvizky, Weill Cornell Medical College, New York Presbyterian Hospital, New York, NY; Ian W. Flinn, Sarah Cannon Research Institute and Tennessee Oncology, Nashville, TN; Robert Rifkin, US Oncology Research/McKesson Specialty Health, The Woodlands, TX; Nashat Gabrail, Gabrail Cancer Center, Canton, OH; Veena Charu, Pacific Cancer Medical Center, Anaheim, CA; Billy Clowney, Santee Hematology/Oncology, Sumter, SC; James Essell, Sarah Cannon Research Institute and Oncology Hematology Care, Cincinnati, OH; Yousuf Gaffar, University of Maryland-St Joseph Medical Center, Towson, MD; Thomas Warr, Clinic Cancer Care, Great Falls, MT; Rachel Neuwirth, Yanyan Zhu, Jennifer Elliott, Dixie-Lee Esseltine, and Liviu Niculescu, Millennium Pharmaceuticals, Cambridge, MA; and James Reeves, Sarah Cannon Research Institute and Florida Cancer Specialists, Fort Myers, FL.
authors.forename: Dixie-Lee
authors.initials: DL
authors.lastname: Esseltine
authors.affiliation: Ruben Niesvizky, Weill Cornell Medical College, New York Presbyterian Hospital, New York, NY; Ian W. Flinn, Sarah Cannon Research Institute and Tennessee Oncology, Nashville, TN; Robert Rifkin, US Oncology Research/McKesson Specialty Health, The Woodlands, TX; Nashat Gabrail, Gabrail Cancer Center, Canton, OH; Veena Charu, Pacific Cancer Medical Center, Anaheim, CA; Billy Clowney, Santee Hematology/Oncology, Sumter, SC; James Essell, Sarah Cannon Research Institute and Oncology Hematology Care, Cincinnati, OH; Yousuf Gaffar, University of Maryland-St Joseph Medical Center, Towson, MD; Thomas Warr, Clinic Cancer Care, Great Falls, MT; Rachel Neuwirth, Yanyan Zhu, Jennifer Elliott, Dixie-Lee Esseltine, and Liviu Niculescu, Millennium Pharmaceuticals, Cambridge, MA; and James Reeves, Sarah Cannon Research Institute and Florida Cancer Specialists, Fort Myers, FL.
authors.forename: Liviu
authors.initials: L
authors.lastname: Niculescu
authors.affiliation: Ruben Niesvizky, Weill Cornell Medical College, New York Presbyterian Hospital, New York, NY; Ian W. Flinn, Sarah Cannon Research Institute and Tennessee Oncology, Nashville, TN; Robert Rifkin, US Oncology Research/McKesson Specialty Health, The Woodlands, TX; Nashat Gabrail, Gabrail Cancer Center, Canton, OH; Veena Charu, Pacific Cancer Medical Center, Anaheim, CA; Billy Clowney, Santee Hematology/Oncology, Sumter, SC; James Essell, Sarah Cannon Research Institute and Oncology Hematology Care, Cincinnati, OH; Yousuf Gaffar, University of Maryland-St Joseph Medical Center, Towson, MD; Thomas Warr, Clinic Cancer Care, Great Falls, MT; Rachel Neuwirth, Yanyan Zhu, Jennifer Elliott, Dixie-Lee Esseltine, and Liviu Niculescu, Millennium Pharmaceuticals, Cambridge, MA; and James Reeves, Sarah Cannon Research Institute and Florida Cancer Specialists, Fort Myers, FL.
authors.forename: James
authors.initials: J
authors.lastname: Reeves
mesh_terms: D000305:Adrenal Cortex Hormones / Q000008:administration & dosage / Q000009:adverse effects; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage* / Q000009:adverse effects; D000069286:Bortezomib / Q000008:administration & dosage* / Q000009:adverse effects; D003153:Community Health Services; D018572:Disease-Free Survival; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D009101:Multiple Myeloma / Q000188:drug therapy* / Q000401:mortality* / Q000473:pathology; D015999:Multivariate Analysis; D011379:Prognosis; D016016:Proportional Hazards Models; D011446:Prospective Studies; D018570:Risk Assessment; D012720:Severity of Illness Index; D016019:Survival Analysis; D013792:Thalidomide / Q000008:administration & dosage / Q000009:adverse effects; D016896:Treatment Outcome
chemical_list: D000305:Adrenal Cortex Hormones; D013792:Thalidomide; D000069286:Bortezomib