title: Phase III trial of bortezomib, cyclophosphamide and dexamethasone (VCD) versus bortezomib, doxorubicin and dexamethasone (PAd) in newly diagnosed myeloma.
abstract: We aimed at demonstrating non-inferiority of bortezomib/cyclophosphamide/dexamethasone (VCD) compared to bortezomib/doxorubicin/dexamethasone (PAd) induction therapy with respect to very good partial response rates or better (⩾VGPR) in 504 newly diagnosed, transplant-eligible multiple myeloma patients. VCD was found to be non-inferior to PAd with respect to ⩾VGPR rates (37.0 versus 34.3%, P=0.001). The rates of progressive disease (PD) were 0.4% (VCD) versus 4.8% (PAd; P=0.003). In the PAd arm, 11 of 12 patients with PD had either renal impairment (creatinine ⩾2 mg/dl) at diagnosis or the cytogenetic abnormality gain 1q21, whereas no PD was observed in these subgroups in the VCD arm. Leukocytopenia/neutropenia (⩾3°) occurred more frequently in the VCD arm (35.2% versus 11.3%, P<0.001). Neuropathy rates (⩾2°) were higher in the PAd group (14.9 versus 8.4%, P=0.03). Serious adverse events, both overall and those related to thromboembolic events, were higher in the PAd group (32.7 versus 24.0%, P=0.04 and 2.8 versus 0.4%, P=0.04). Stem cell collection was not impeded by VCD. VCD is as effective as PAd in terms of achieving ⩾VGPR rates with fewer PD and has a favorable toxicity profile. Therefore, VCD is preferable to PAd as induction therapy.
authors: Department of Internal Medicine V, University Hospital Heidelberg and National Center for Tumor Diseases (NCT) Heidelberg on behalf of the German-Speaking Myeloma Multicenter Group (GMMG), Heidelberg, Germany.
authors: E K
authors: EK
authors: Mai
authors: Department of Internal Medicine V, University Hospital Heidelberg and National Center for Tumor Diseases (NCT) Heidelberg on behalf of the German-Speaking Myeloma Multicenter Group (GMMG), Heidelberg, Germany.
authors: U
authors: U
authors: Bertsch
authors: Department of Hematology, University Hospital Essen, Essen, Germany.
authors: J
authors: J
authors: Dürig
authors: Division of Biostatistics, German Cancer Research Center (DKFZ) Heidelberg, Heidelberg, Germany.
authors: C
authors: C
authors: Kunz
authors: Department of Internal Medicine III, Klinikum Chemnitz, Chemnitz, Germany.
authors: M
authors: M
authors: Haenel
authors: Medical Clinic, Charité University Medicine Berlin, Berlin, Germany.
authors: I W
authors: IW
authors: Blau
authors: Department of Internal Medicine III, University Medical Center Mainz, Mainz, Germany.
authors: M
authors: M
authors: Munder
authors: Institute of Human Genetics, University of Heidelberg, Heidelberg, Germany.
authors: A
authors: A
authors: Jauch
authors: Coordination Centers for Clinical Trials (KKS), University Hospital Heidelberg, Heidelberg, Germany.
authors: B
authors: B
authors: Schurich
authors: Division of Biostatistics, German Cancer Research Center (DKFZ) Heidelberg, Heidelberg, Germany.
authors: T
authors: T
authors: Hielscher
authors: Department of Internal Medicine V, University Hospital Heidelberg, Heidelberg, Germany.
authors: M
authors: M
authors: Merz
authors: Department of Internal Medicine V, University Hospital Heidelberg and National Center for Tumor Diseases (NCT) Heidelberg on behalf of the German-Speaking Myeloma Multicenter Group (GMMG), Heidelberg, Germany.
authors: B
authors: B
authors: Huegle-Doerr
authors: Department of Internal Medicine V, University Hospital Heidelberg and National Center for Tumor Diseases (NCT) Heidelberg on behalf of the German-Speaking Myeloma Multicenter Group (GMMG), Heidelberg, Germany.
authors: A
authors: A
authors: Seckinger
authors: Department of Internal Medicine V, University Hospital Heidelberg and National Center for Tumor Diseases (NCT) Heidelberg on behalf of the German-Speaking Myeloma Multicenter Group (GMMG), Heidelberg, Germany.
authors: D
authors: D
authors: Hose
authors: Department of Internal Medicine V, University Hospital Heidelberg, Heidelberg, Germany.
authors: J
authors: J
authors: Hillengass
authors: Department of Internal Medicine V, University Hospital Heidelberg, Heidelberg, Germany.
authors: M S
authors: MS
authors: Raab
authors: Department of Internal Medicine V, University Hospital Heidelberg, Heidelberg, Germany.
authors: K
authors: K
authors: Neben
authors: Department of Hematology and Oncology, Katholisches Krankenhaus Hagen, Hagen, Germany.
authors: H-W
authors: HW
authors: Lindemann
authors: Department of Hematology, Asklepios Hospital St. Georg Hamburg, Hamburg, Germany.
authors: M
authors: M
authors: Zeis
authors: Department of Hematology and Oncology, Helios Hospital Berlin Buch, Berlin, Germany.
authors: C
authors: C
authors: Gerecke
authors: Center for Integrated Oncology, University Hospital Bonn, Bonn, Germany.
authors: I G H
authors: IG
authors: Schmidt-Wolf
authors: Department of Hematology, Oncology and Immunology, University Hospital Tübingen, Tübingen, Germany.
authors: K
authors: K
authors: Weisel
authors: Department of Internal Medicine I, University Hospital Köln, Köln, Germany.
authors: C
authors: C
authors: Scheid
authors: Department of Hematology and Oncology, Asklepios Hospital Hamburg Altona, Hamburg, Germany.
authors: H
authors: H
authors: Salwender
authors: Department of Internal Medicine V, University Hospital Heidelberg and National Center for Tumor Diseases (NCT) Heidelberg on behalf of the German-Speaking Myeloma Multicenter Group (GMMG), Heidelberg, Germany.
authors: H
authors: H
authors: Goldschmidt
mesh_terms: D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D001897:Boronic Acids / Q000008:administration & dosage; D000069286:Bortezomib; D003520:Cyclophosphamide / Q000008:administration & dosage; D003907:Dexamethasone / Q000008:administration & dosage; D004317:Doxorubicin / Q000008:administration & dosage; D005260:Female; D005500:Follow-Up Studies; D019650:Hematopoietic Stem Cell Mobilization; D006801:Humans; D060828:Induction Chemotherapy; D008297:Male; D008875:Middle Aged; D009101:Multiple Myeloma / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D009367:Neoplasm Staging; D011379:Prognosis; D011446:Prospective Studies; D011719:Pyrazines / Q000008:administration & dosage; D012074:Remission Induction; D015996:Survival Rate
chemical_list: D001897:Boronic Acids; D011719:Pyrazines; D000069286:Bortezomib; D003907:Dexamethasone; D004317:Doxorubicin; D003520:Cyclophosphamide