title: A systematic review of phase-II trials of thalidomide monotherapy in patients with relapsed or refractory multiple myeloma.
abstract: The activity of thalidomide in relapsed or refractory multiple myeloma is widely accepted but not yet demonstrated in a randomised-controlled trial. A systematic review of the published clinical trials of these patients could reduce the possible bias of single phase-II studies. A systematic search identified 42 communications reporting on 1674 patients. Thirty-two trials used an escalating dosing regimen and four a fixed dose regimen (one dose with 50 mg/d, three doses with 200 mg/d). The target dose in the dose escalating trials was 800 mg/d in 17 trials, 400-600 mg/d in 10 and 200 mg/d in one trial. The intention-to-treat population for efficacy was 1629 patients with a median age of 62 years. The complete and partial (>50% reduction in monoclonal protein) response rate was 29.4% (95%-confidence interval, 27-32%). The rates for minor responses or stable disease were 13.8% (12-16%) and 11.0% (9-13%). Progressive disease was reported in 9.9% (8-11%). The median overall survival from all trials was reported at 14 months. Severe adverse events (grade III-IV) included somnolence 11%, constipation 16%, neuropathy 6%, rash 3%, thrombo-embolism 3%, cardiac 2%. In conclusion, thalidomide monotherapy achieved complete and partial responses in 29.4% of patients with relapsed or refractory multiple myeloma.
authors.affiliation: Department of Internal Medicine I, University of Bonn, Bonn, Germany. glasmacher@uni-bonn.de
authors.forename: Axel
authors.initials: A
authors.lastname: Glasmacher
authors.forename: Corinna
authors.initials: C
authors.lastname: Hahn
authors.forename: Florian
authors.initials: F
authors.lastname: Hoffmann
authors.forename: Ralph
authors.initials: R
authors.lastname: Naumann
authors.forename: Hartmut
authors.initials: H
authors.lastname: Goldschmidt
authors.forename: Marie
authors.initials: M
authors.lastname: von Lilienfeld-Toal
authors.forename: Katjana
authors.initials: K
authors.lastname: Orlopp
authors.forename: Ingo
authors.initials: I
authors.lastname: Schmidt-Wolf
authors.forename: Marcus
authors.initials: M
authors.lastname: Gorschlüter
mesh_terms: D017322:Clinical Trials, Phase II as Topic; D003625:Data Collection; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D006801:Humans; D007166:Immunosuppressive Agents / Q000009:adverse effects / Q000627:therapeutic use*; D009101:Multiple Myeloma / Q000188:drug therapy* / Q000401:mortality; D009364:Neoplasm Recurrence, Local / Q000188:drug therapy*; D010523:Peripheral Nervous System Diseases / Q000139:chemically induced; D015996:Survival Rate; D013792:Thalidomide / Q000009:adverse effects / Q000627:therapeutic use*; D016896:Treatment Outcome
chemical_list: D007166:Immunosuppressive Agents; D013792:Thalidomide