Cyclophosphamide, thalidomide, and dexamethasone (CTD) as initial therapy for patients with multiple myeloma unsuitable for autologous transplantation.

Abstract

As part of the randomized MRC Myeloma IX trial, we compared an attenuated regimen of cyclophosphamide, thalidomide, and dexamethasone (CTDa; n = 426) with melphalan and prednisolone (MP; n = 423) in patients with newly diagnosed multiple myeloma ineligible for autologous stem-cell transplantation. The primary endpoints were overall response rate, progression-free survival, and overall survival (OS). The overall response rate was significantly higher with CTDa than MP (63.8% vs 32.6%; P < .0001), primarily because of increases in the rate of complete responses (13.1% vs 2.4%) and very good partial responses (16.9% vs 1.7%). Progression-free survival and OS were similar between groups. In this population, OS correlated with the depth of response (P < .0001) and favorable interphase fluorescence in situ hybridization profile (P < .001). CTDa was associated with higher rates of thromboembolic events, constipation, infection, and neuropathy than MP. In elderly patients with newly diagnosed multiple myeloma (median age, 73 years), CTDa produced higher response rates than MP but was not associated with improved survival outcomes. We highlight the importance of cytogenetic profiling at diagnosis and effective management of adverse events. This trial was registered at International Standard Randomized Controlled Trials Number as #68454111.

• Authors: Gareth J Morgan, Faith E Davies, Walter M Gregory, Nigel H Russell, Sue E Bell, Alexander J Szubert, Nuria Navarro Coy, Gordon Cook, Sylvia Feyler, Jenny L Byrne, Huw Roddie, Claudius Rudin, Mark T Drayson, Roger G Owen, Fiona M Ross, Graham H Jackson, J Anthony Child, NCRI Haematological Oncology Study Group
• Journal: Blood (Blood) Vol. 118 Issue 5 Pg. 1231-8 (Aug 04 2011) ISSN: 1528-0020 [Electronic] United States
• PMID: 21652683 (Publication Type: Clinical Trial, Phase III, Journal Article, Multicenter Study, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)

Chemical References

• Thalidomide
• Dexamethasone
• Cyclophosphamide

Topics

• Aged
• Aged, 80 and over
• Antineoplastic Combined Chemotherapy Protocols (adverse effects, therapeutic use)
• Cyclophosphamide (administration & dosage, adverse effects)
• Dexamethasone (administration & dosage, adverse effects)
• Eligibility Determination
• Female
• Hematopoietic Stem Cell Transplantation
• Humans
• Male
• Middle Aged
• Multiple Myeloma (drug therapy, therapy)
• Neoadjuvant Therapy
• Patient Selection
• Thalidomide (administration & dosage, adverse effects)
• Transplantation, Autologous