title: Phase II study of dose-attenuated bortezomib, cyclophosphamide and dexamethasone ("VCD-Lite") in very old or otherwise toxicity-vulnerable adults with newly diagnosed multiple myeloma.
abstract: OBJECTIVE
  Multiple myeloma (MM) primarily strikes older adults, but full-dose chemotherapy such as bortezomib (Velcade), cyclophosphamide and dexamethasone (VCD) is often excessively toxic to very old or frail adults and those with substantial comorbidities. We piloted dose-attenuated VCD ("VCD-Lite") in such vulnerable adults with newly diagnosed MM (NDMM).
  
  
  METHODS
  Subjects with NDMM and a high risk of therapy-related toxicity due to factors above received bortezomib 1.3mg/m2subcutaneously, cyclophosphamide 300mg/m2and dexamethasone 40mg orally, all on days 1, 8, and 15 of a 28day cycle for eight cycles, followed by indefinite, alternating bortezomib and lenalidomide maintenance. Toxicity, overall response rate (ORR), progression-free and overall survival (PFS and OS) were determined. The Cancer and Aging Research Group geriatric assessment (CARG GA) was administered at baseline in an exploratory manner as a predictor of severe toxicity.
  
  
  RESULTS
  14 patients went on the study, which was closed early due to slow accrual. Intention-to-treat ORR was 64%. 64% of patients experienced grade ≥3 adverse events, the majority of which were unlikely therapy-related. Median PFS was 24.2months and OS 29.7months, with 14%, 36% and 29% of patients discontinuing study drugs due to toxicity, MM progression and other reasons respectively. Baseline CARG GA was successfully completed by all subjects but one.
  
  
  CONCLUSIONS
  VCD-Lite is a viable option for vulnerable adults with NDMM. CARG GA is feasible. Further studies to optimize therapy and to explore CARG GA as a toxicity predictor are vital.
authors.affiliation: Multiple Myeloma and Amyloidosis Program, Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, NC, United States; Division of Hematological Malignancies and Cellular Therapy, Duke Cancer Institute, Durham, NC, United States. Electronic address: Sascha_tuchman@med.unc.edu.
authors.forename: Sascha A
authors.initials: SA
authors.lastname: Tuchman
authors.affiliation: Division of Hematological Malignancies and Cellular Therapy, Duke Cancer Institute, Durham, NC, United States.
authors.forename: Joseph O
authors.initials: JO
authors.lastname: Moore
authors.affiliation: Division of Hematological Malignancies and Cellular Therapy, Duke Cancer Institute, Durham, NC, United States.
authors.forename: Carlos D
authors.initials: CD
authors.lastname: DeCastro
authors.affiliation: Department of Biostatistics and Bioinformatics, Duke Cancer Institute, Durham, NC, United States.
authors.forename: Zhiguo
authors.initials: Z
authors.lastname: Li
authors.affiliation: Division of Hematological Malignancies and Cellular Therapy, Duke Cancer Institute, Durham, NC, United States.
authors.forename: Emily
authors.initials: E
authors.lastname: Sellars
authors.affiliation: Division of Hematological Malignancies and Cellular Therapy, Duke Cancer Institute, Durham, NC, United States.
authors.forename: Yubin
authors.initials: Y
authors.lastname: Kang
authors.affiliation: Division of Hematological Malignancies and Cellular Therapy, Duke Cancer Institute, Durham, NC, United States.
authors.forename: Gwynn
authors.initials: G
authors.lastname: Long
authors.affiliation: Division of Hematological Malignancies and Cellular Therapy, Duke Cancer Institute, Durham, NC, United States.
authors.forename: Cristina G
authors.initials: CG
authors.lastname: Gasparetto
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; 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; D004305:Dose-Response Relationship, Drug; D057239:Early Termination of Clinical Trials; D005260:Female; D015577:Geriatric Assessment; D006801:Humans; D060828:Induction Chemotherapy / Q000379:methods; D057194:Intention to Treat Analysis; D053208:Kaplan-Meier Estimate; D008297:Male; D009101:Multiple Myeloma / Q000188:drug therapy* / Q000473:pathology; D012307:Risk Factors
chemical_list: D000069286:Bortezomib; D003907:Dexamethasone; D003520:Cyclophosphamide
keywords: Chemotherapy; Elderly; Frail; Geriatric assessment; Myeloma; Senior; Toxicity