Thalidomide has been shown to be active against multiple myeloma, even in patients who have relapsed after repeated cycles of high-dose chemotherapy, say researchers from the US.
Writing on behalf of the Myeloma and Lymphoma Programme, Dr Seema Singhal (University of South Carolina) and colleagues report the results obtained when 84 patients with advanced and refractory myeloma (76 of whom had had a relapse after high-dose chemotherapy) took thalidomide, given for its immunomodulatory effects. The initial dose was 200mg at night, which was gradually increased to a maximum dose of 800mg daily. Only 47 per cent of subjects were able to tolerate the maximum dose. Nine patients were unable to tolerate thalidomide and discontinued treatment.
The authors describe the primary end-point of the trial as a decline of at least 25 per cent in the level of paraprotein (ie, the myeloma protein in serum and Bence-Jones protein in urine) on two occasions at least six weeks apart, as this indicated an antitumour effect.
The total rate of response was 32 per cent (27 patients); two patients had a complete remission.
Ninety-nine per cent of patients experienced side effects but most were mild or moderate. Those that were most common included constipation, weakness or fatigue and somnolence, which occurred in one-third or more patients. Reducing the dose of thalidomide alleviated the side effects in most cases.
The median event-free survival for all 84 patients was three months and after up to 18 months of follow-up, 36 patients had died. These included 30 non-responders whose disease had progressed or who had suffered complications following salvage therapy. The results are published in the New England Journal of Medicine (1999;341:1565).