title: Bortezomib for patients with previously untreated multiple myeloma: a systematic review and meta-analysis of randomized controlled trials.
abstract: Multiple myeloma (MM) is an incurable disease with a poor survival, which has not been affected even by high-dose chemotherapy. This systematic review was performed to assess the efficacy and safety of the novel agent bortezomib for patients with previously untreated MM. We systematically searched biomedical literature databases and identified randomized controlled trials (RCTs) comparing bortezomib with placebo, no bortezomib, or other active agents for patients with previously untreated MM. Overall survival (OS), reported as hazard ratio (HR) with 95% confidence interval (CI), was the primary outcome measure. The secondary outcomes included time to progression (TTP), progression-free survival (PFS), and response rates. Five RCTs involving 2,728 patients were included. Three trials compared bortezomib with no bortezomib, and two compared bortezomib with other active agents (vincristine ± adriamycin-based chemotherapy). All included RCTs had methodological shortcomings, including no or unclear allocation concealment and blinding. Compared with no bortezomib or vincristine-based chemotherapy, the bortezomib-based regimen significantly improved the OS of patients with previously untreated MM. HR was 0.71 (95% CI 0.55-0.93) and 0.77 (95% CI 0.60-0.99), respectively. However, when compared with the vincristine + adriamycin-based regimen, the OS was similar (HR = 0.87, 95% CI 0.57-1.33). TTP, PFS, and response rates were also improved in patients receiving bortezomib-based regimen. However, the risk of peripheral neuropathy was found to be significantly higher. In summary, bortezomib appears to improve survival and response rates of patients with previously untreated MM in spite of higher risk of peripheral neuropathy.
authors: Department of Hematology and Rheumatology, The First Affiliated Hospital of Fujian Medical University, Chating, Fuzhou, 350005, China.
authors: Zhiyong
authors: Z
authors: Zeng
authors: Junfang
authors: J
authors: Lin
authors: Junmin
authors: J
authors: Chen
mesh_terms: D000970:Antineoplastic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use; D001897:Boronic Acids / Q000009:adverse effects / Q000627:therapeutic use*; D000069286:Bortezomib; D003131:Combined Modality Therapy; D018450:Disease Progression; D018572:Disease-Free Survival; D004317:Doxorubicin / Q000008:administration & dosage / Q000009:adverse effects; D006801:Humans; D009101:Multiple Myeloma / Q000188:drug therapy* / Q000401:mortality / Q000601:surgery; D010523:Peripheral Nervous System Diseases / Q000139:chemically induced; D011480:Protease Inhibitors / Q000009:adverse effects / Q000627:therapeutic use*; D011719:Pyrazines / Q000009:adverse effects / Q000627:therapeutic use*; D016032:Randomized Controlled Trials as Topic / Q000706:statistics & numerical data*; D012074:Remission Induction; D033581:Stem Cell Transplantation; D016019:Survival Analysis; D014182:Transplantation, Autologous; D014750:Vincristine / Q000008:administration & dosage / Q000009:adverse effects
chemical_list: D000970:Antineoplastic Agents; D001897:Boronic Acids; D011480:Protease Inhibitors; D011719:Pyrazines; D014750:Vincristine; D000069286:Bortezomib; D004317:Doxorubicin