Thalidomide for the treatment of refractory multiple myeloma: association of plasma concentrations of thalidomide and angiogenic growth factors with clinical outcome.
Recent reports showed that thalidomide has anti-angiogenic activity and is effective for the treatment of refractory multiple myeloma (MM). We examined the relationship between the clinical efficacy and adverse effects of thalidomide and the plasma concentrations of this drug as well as angiogenic growth factors in refractory MM. Ten out of twenty-four evaluable patients (42%) showed more than 25% reduction of M-protein, and eight (33%) achieved more than 50% reduction. These changes were associated with restoration of anemia and recovery of normal immunoglobulin level. Somnolence and headache, constipation, peripheral neuropathy and skin rash were frequently observed, but were well tolerated. However, grade 2 - 4 severe neutropenia was also observed in nine cases. These adverse effects other than neutropenia occurred more frequently in the patients with higher plasma concentrations of thalidomide (2.0 microg/ml at 12 h after the last administration) and were readily alleviated by dose reduction. In contrast, neutropenia developed regardless of the plasma concentration. Plasma concentrations of angiogenic growth factors were frequently elevated before treatment. After thalidomide treatment, these growth factor levels tend to decrease to near-normal ranges in responders but were still high in most non-responders. After thalidomide treatment, plasma vascular endothelial growth factor (VEGF) level was significantly reduced in responders (P = 0.025), but not in non-responders (P = 0.37). Reduction of plasma VEGF level might be an important indicator for anti-myeloma effect of thalidomide.
D000328:Adult; D000368:Aged; D016228:Endothelial Growth Factors / Q000097:blood; D005260:Female; D016222:Fibroblast Growth Factor 2 / Q000097:blood; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000097:blood; D008222:Lymphokines / Q000097:blood; D008297:Male; D008875:Middle Aged; D009101:Multiple Myeloma / Q000097:blood / Q000188:drug therapy*; D013792:Thalidomide / Q000009:adverse effects / Q000097:blood / Q000627:therapeutic use*; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors
D016228:Endothelial Growth Factors; D036341:Intercellular Signaling Peptides and Proteins; D008222:Lymphokines; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors; D016222:Fibroblast Growth Factor 2; D013792:Thalidomide