@article{3078300,
    title = "Effect of induction therapy with lenalidomide, doxorubicin and dexamethasone on bone remodeling and angiogenesis in newly diagnosed multiple myeloma",
    author = "Terpos, E. and Katodritou, E. and Symeonidis, A. and Zagouri, F. and Gerofotis, A. and Christopoulou, G. and Gavriatopoulou, M. and Christoulas, D. and Ntanasis-Stathopoulos, I. and Kourakli, A. and Konstantinidou, P. and Kastritis, E. and Dimopoulos, M.A.",
    journal = "International Journal  of Cancer",
    year = "2019",
    volume = "145",
    number = "2",
    pages = "559-568",
    publisher = "Wiley-Liss, Inc.",
    issn = "0020-7136",
    doi = "10.1002/ijc.32125",
    keywords = "acid phosphatase tartrate resistant isoenzyme;  acid phosphatase tartrate resistant isoenzyme 5b;  alkaline phosphatase;  angiogenin;  collagen type 1;  dexamethasone;  doxorubicin;  fibroblast growth factor 2;  lenalidomide;  osteocalcin;  procollagen C proteinase;  unclassified drug;  vasculotropin;  alkaline phosphatase;  angiogenic protein;  angiogenin;  antineoplastic agent;  BGLAP protein, human;  dexamethasone;  doxorubicin;  fibroblast growth factor 2;  lenalidomide;  osteocalcin;  pancreatic ribonuclease;  peptide fragment;  procollagen;  procollagen type IIA amino-terminal peptide;  vasculotropin A;  VEGFA protein, human, acute kidney failure;  adult;  aged;  anemia;  angiogenesis;  Article;  bone metabolism;  bone remodeling;  cancer survival;  clinical article;  controlled clinical trial;  controlled study;  drug efficacy;  drug safety;  fatigue;  febrile neutropenia;  female;  fever;  follow up;  fracture;  human;  hypocalcemia;  induction chemotherapy;  leukopenia;  low back pain;  lung embolism;  male;  multiple cycle treatment;  multiple myeloma;  open study;  osteolysis;  phase 2 clinical trial;  priority journal;  respiratory tract infection;  stem cell;  treatment outcome;  treatment response;  clinical trial;  combination drug therapy;  drug effect;  gene expression regulation;  induction chemotherapy;  metabolism;  middle aged;  multiple myeloma, Adult;  Aged;  Alkaline Phosphatase;  Angiogenic Proteins;  Antineoplastic Combined Chemotherapy Protocols;  Bone Resorption;  Dexamethasone;  Doxorubicin;  Drug Therapy, Combination;  Female;  Fibroblast Growth Factor 2;  Gene Expression Regulation, Neoplastic;  Humans;  Induction Chemotherapy;  Lenalidomide;  Male;  Middle Aged;  Multiple Myeloma;  Osteocalcin;  Peptide Fragments;  Procollagen;  Ribonuclease, Pancreatic;  Treatment Outcome;  Vascular Endothelial Growth Factor A",
    abstract = "There is limited data regarding the efficacy and safety of lenalidomide, adriamycin and dexamethasone (RAD) combination on newly diagnosed multiple myeloma (NDMM) patients. There is also scarce information about the effect of lenalidomide on bone metabolism and angiogenesis in NDMM. Thus, we conducted a Phase 2 study to evaluate the efficacy and safety of RAD regimen as induction in transplant-eligible NDMM patients and we studied the effects on bone metabolism and angiogenesis. A total of 45 patients were enrolled. Following four cycles of RAD, the overall response rate was 66.7% and after a median follow up of 29.1 months (range 21.0–34.9), the median survival outcomes have not been reached yet. RAD had a favorable toxicity profile and did not impair stem cell collection. RAD significantly reduced bone resorption markers CTX (p = 0.03) and TRACP-5b (p < 0.01). Interestingly, RAD also increased bone formation markers bone-specific alkaline phosphatase (p = 0.036), procollagen type 1 amino-terminal propeptide (p = 0.028) and osteocalcin (p = 0.026), which has not been described before with lenalidomide-containing regimens in the absence of bortezomib coadministration. Furthermore, the angiogenic cytokines VEGF (p = 0.01), angiogenin (p = 0.02) and bFGF (p < 0.01) were significantly reduced post-RAD induction. Our results suggest that RAD is an effective induction regimen before autologous stem cell transplantation with beneficial effects on bone metabolism and angiogenesis. © 2019 UICC"
}