title: A randomized study (WOS MM1) comparing the oral regime Z-Dex (idarubicin and dexamethasone) with vincristine, adriamycin and dexamethasone as induction therapy for newly diagnosed patients with multiple myeloma.
abstract: Whilst infusional vincristine, adriamycin and dexamethasone (VAD) is an effective treatment for patients with multiple myeloma (MM), administration may be complicated by line-associated infections and thromboses. The oral regime, Z-Dex (idarubicin and dexamethasone) has been shown to be efficacious in MM. We conducted a randomized study comparing Z-Dex with VAD as induction therapy in newly diagnosed MM patients. A total of 106 patients (median age, 56 years; range: 37-73; Durie-Salmon stage II/III) were randomized to receive four to six cycles of Z-Dex or VAD. Central line complications were reported in 38 patients on 57 cycles, primarily because of infection. Neutropenia (all grades) was more common in the Z-Dex arm (P = 0.009) although grade III/IV neutropenia was not significantly different between the treatment groups (P = 0.06). Infections (all grades) were more commonly seen in the VAD arm (P = 0.001) although grade III/IV infections were not significantly different between the two groups (P = 0.081). The responses to therapy (complete/partial response) in evaluable patients were: VAD 74% vs. Z-Dex 58%, with an estimated difference in response of 16% (95% CI -2-33, P = 0.075). VAD recipients (15%) suffered early treatment-related mortality compared with 12% of Z-Dex recipients. Overall, 45 patients have died: disease progression (Z-Dex n = 13, VAD n = 10), regimen-related toxicity (Z-Dex n = 2, VAD n = 2), infection (Z-Dex n = 0, VAD n = 3), other causes (Z-Dex n = 7, VAD n = 2), unknown (Z-Dex n = 3, VAD n = 2). This study demonstrated that Z-Dex might be a suitable oral alternative to VAD for treating newly diagnosed MM patients, although definitive evidence for equivalence is not provided.
authors.affiliation: Leeds Teaching Hospitals Trust, Leeds, UK. gordon.cook@leedsth.nhs.uk
authors.forename: G
authors.initials: G
authors.lastname: Cook
authors.forename: R E
authors.initials: RE
authors.lastname: Clark
authors.forename: T C M
authors.initials: TC
authors.lastname: Morris
authors.forename: M
authors.initials: M
authors.lastname: Robertson
authors.forename: N P
authors.initials: NP
authors.lastname: Lucie
authors.forename: S
authors.initials: S
authors.lastname: Anderson
authors.forename: J
authors.initials: J
authors.lastname: Paul
authors.forename: I M
authors.initials: IM
authors.lastname: Franklin
mesh_terms: D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D003907:Dexamethasone / Q000008:administration & dosage / Q000009:adverse effects; D018572:Disease-Free Survival; D004317:Doxorubicin / Q000008:administration & dosage / Q000009:adverse effects; D005260:Female; D006801:Humans; D015255:Idarubicin / Q000008:administration & dosage / Q000009:adverse effects; D008297:Male; D008875:Middle Aged; D009101:Multiple Myeloma / Q000188:drug therapy*; D015996:Survival Rate; D016896:Treatment Outcome; D014750:Vincristine / Q000008:administration & dosage / Q000009:adverse effects
chemical_list: D014750:Vincristine; D003907:Dexamethasone; D004317:Doxorubicin; D015255:Idarubicin