A systematic review of phase‐II trials of thalidomide monotherapy in patients with relapsed or refractory multiple myeloma

• Published in: British journal of haematology 2006-03, Vol.132 (5), p.584-593
• Main Authors: Glasmacher, Axel, Hahn, Corinna, Hoffmann, Florian, Naumann, Ralph, Goldschmidt, Hartmut, Lilienfeld‐Toal, Marie, Orlopp, Katjana, Schmidt‐Wolf, Ingo, Gorschlüter, Marcus
• Format: Article
• Language: English
• Subjects: Biological and medical sciences; Clinical Trials, Phase II as Topic; Data Collection; Dose-Response Relationship, Drug; Drug Administration Schedule; Hematologic and hematopoietic diseases; Hematology; Humans; Immunodeficiencies. Immunoglobulinopathies; Immunoglobulinopathies; Immunopathology; Immunosuppressive Agents - adverse effects; Immunosuppressive Agents - therapeutic use; Leukemias. Malignant lymphomas. Malignant reticulosis. Myelofibrosis; Medical sciences; multiple myeloma; Multiple Myeloma - drug therapy; Multiple Myeloma - mortality; Neoplasm Recurrence, Local - drug therapy; Peripheral Nervous System Diseases - chemically induced; Survival Rate; systematic review; thalidomide; Thalidomide - adverse effects; Thalidomide - therapeutic use; Treatment Outcome
• ISSN: 0007-1048; 1365-2141
• DOI: 10.1111/j.1365-2141.2005.05914.x

Summary 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.