title: Cyclophosphamide, thalidomide, and dexamethasone as induction therapy for newly diagnosed multiple myeloma patients destined for autologous stem-cell transplantation: MRC Myeloma IX randomized trial results.
abstract: BACKGROUND
  Thalidomide is active in multiple myeloma and is associated with minimal myelosuppression, making it a good candidate for induction therapy prior to high-dose therapy with autologous stem-cell transplantation.
  
  
  METHODS
  Oral cyclophosphamide, thalidomide, and dexamethasone was compared with infusional cyclophosphamide, vincristine, doxorubicin, and dexamethasone in patients with newly diagnosed multiple myeloma.
  
  
  RESULTS
  The post-induction overall response rate (≥ partial response) for the intent-to-treat population was significantly higher with cyclophosphamide-thalidomide-dexamethasone (n=555) versus cyclophosphamide-vincristine-doxorubicin-dexamethasone (n=556); 82.5% versus 71.2%; odds ratio 1.91; 95% confidence interval 1.44-2.55; P<0.0001. The complete response rates were 13.0% with cyclophosphamide-thalidomide-dexamethasone and 8.1% with cyclophos-phamide-vincristine-doxorubicin-dexamethasone (P=0.0083), with this differential response being maintained in patients who received autologous stem-cell transplantation (post-transplant complete response 50.0% versus 37.2%, respectively; P=0.00052). Cyclophosphamide-thalidomide-dexamethasone was non-inferior to cyclophosphamide-vincristine-doxorubicin-dexamethasone for progression-free and overall survival, and there was a trend toward a late survival benefit with cyclophosphamide-thalidomide-dexamethasone in responders. A trend toward an overall survival advantage for cyclophosphamide-thalidomide-dexamethasone over cyclophosphamide-vincristine-doxorubicin-dexamethasone was also observed in a subgroup of patients with favorable interphase fluorescence in situ hybridization. Compared with cyclophosphamide-vincristine-doxorubicin-dexamethasone, cyclophosphamide-thalidomide-dexamethasone was associated with more constipation and somnolence, but a lower incidence of cytopenias.
  
  
  CONCLUSIONS
  The cyclophosphamide-thalidomide-dexamethasone regimen showed improved response rates and was not inferior in terms of survival outcomes to the standard infusional regimen of cyclophosphamide-vincristine-doxorubicin-dexamethasone. Based on its oral administration and the reduced incidence of infection and cytopenia, cyclophosphamide-thalidomide-dexa-methasone may be considered an effective induction therapy option for patients with newly diagnosed multiple myeloma. (ISRCTN: 68454111).
authors: The Institute of Cancer Research, Royal Marsden Hospital, London, UK. gareth.morgan@icr.ac.uk
authors: Gareth J
authors: GJ
authors: Morgan
authors: Faith E
authors: FE
authors: Davies
authors: Walter M
authors: WM
authors: Gregory
authors: Sue E
authors: SE
authors: Bell
authors: Alexander J
authors: AJ
authors: Szubert
authors: Nuria
authors: N
authors: Navarro Coy
authors: Gordon
authors: G
authors: Cook
authors: Sylvia
authors: S
authors: Feyler
authors: Peter R E
authors: PR
authors: Johnson
authors: Claudius
authors: C
authors: Rudin
authors: Mark T
authors: MT
authors: Drayson
authors: Roger G
authors: RG
authors: Owen
authors: Fiona M
authors: FM
authors: Ross
authors: Nigel H
authors: NH
authors: Russell
authors: Graham H
authors: GH
authors: Jackson
authors: J Anthony
authors: JA
authors: Child
mesh_terms: D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D003520:Cyclophosphamide / Q000008:administration & dosage; D003907:Dexamethasone / Q000008:administration & dosage; D005260:Female; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D060828:Induction Chemotherapy; D008297:Male; D008875:Middle Aged; D009101:Multiple Myeloma / Q000188:drug therapy / Q000401:mortality / Q000628:therapy*; D016019:Survival Analysis; D013792:Thalidomide / Q000008:administration & dosage; D014182:Transplantation, Autologous; D016896:Treatment Outcome
chemical_list: D013792:Thalidomide; D003907:Dexamethasone; D003520:Cyclophosphamide