title: Cyclophosphamide plus dexamethasone is an efficient initial treatment before high-dose melphalan and autologous stem cell transplantation in patients with newly diagnosed multiple myeloma: results of a randomized comparison with vincristine, doxorubicin, and dexamethasone.
abstract: BACKGROUND
  Today, intensive therapy that includes high-dose melphalan with autologous stem cell transplantation (ASCT) is considered standard therapy in younger patients with newly diagnosed myeloma. When the current trial was initiated, combined vincristine, doxorubicin, and dexamethasone (VAD) was the most commonly used induction therapy before ASCT and yielded rapid major responses without interfering with stem cell harvest. However, the administration of VAD demands a central venous access, and well-described toxicities are associated with the therapy. This randomized trial, which was initiated in 2001 by the Nordic Myeloma Study Group, was an attempt to bring a larger portion of patients to ASCT more quickly.
  
  
  METHODS
  Patients were randomized to receive either 3 cycles of VAD or 2 courses of cyclophosphamide plus dexamethasone (Cy-Dex) (cyclophosphamide at a dose of 1000 mg/m(2) on Day 1 and dexamethasone at a dose of 40 mg per day on Days 1-4 and 9-12, repeated on Day 22) as initial therapy followed by stem cell mobilization, harvest, and finally ASCT.
  
  
  RESULTS
  No significant difference was observed in the proportion of patients undergoing ASCT (VAD [86%] vs Cy-Dex [87%]). During the first 4 months after the initiation of therapy, the mortality rates were 5.8% for VAD and 1.9% for Cy-Dex (P = .08). The response rates after ASCT were comparable (partial response or better: VAD: 80% vs Cy-Dex: 81%). In both groups, the median event-free survival was 29 months, and the overall survival rate at 3 years was 75%.
  
  
  CONCLUSIONS
  The current results indicated that Cy-Dex before ASCT has efficacy comparable to that of VAD. It also demonstrated that a short course of alkylator therapy using cyclophosphamide does not affect stem cell harvest or transplantation.
authors.affiliation: Department of Hematology, Sahlgrenska University Hospital, Gothenburg, Sweden. henrik.mellqvist@vgregion.se
authors.forename: Ulf-Henrik
authors.initials: UH
authors.lastname: Mellqvist
authors.forename: Stig
authors.initials: S
authors.lastname: Lenhoff
authors.forename: Hans E
authors.initials: HE
authors.lastname: Johnsen
authors.forename: Martin
authors.initials: M
authors.lastname: Hjorth
authors.forename: Erik
authors.initials: E
authors.lastname: Holmberg
authors.forename: Gunnar
authors.initials: G
authors.lastname: Juliusson
authors.forename: Jon Magnus
authors.initials: JM
authors.lastname: Tangen
authors.forename: Jan
authors.initials: J
authors.lastname: Westin
mesh_terms: D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D003131:Combined Modality Therapy; D003520:Cyclophosphamide / Q000008:administration & dosage*; D003907:Dexamethasone / Q000008:administration & dosage*; D004317:Doxorubicin / Q000008:administration & dosage; D004334:Drug Administration Schedule; D005260:Female; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D008297:Male; D008558:Melphalan; D008875:Middle Aged; D009101:Multiple Myeloma / Q000628:therapy*; D015996:Survival Rate; D014750:Vincristine / Q000008:administration & dosage*
chemical_list: D014750:Vincristine; D003907:Dexamethasone; D004317:Doxorubicin; D003520:Cyclophosphamide; D008558:Melphalan