Commentary on Abstracts #613, #1384, and #599

In the phase II study of thalidomide (Thalomid) in the treatment of recurrent glioblastoma multiforme, Marx et al (abstract #613) concluded that there was no correlation with vascular endothelial growth factor (VEGF) levels and response or prognosis. Levels of VEGF were measured but not reported by Minor et al (abstract #1384) in the treatment of metastatic renal cell carcinoma. Vredenburgh et al (abstract #599) reported their experience using thalidomide in the setting of minimal residual disease in patients with metastatic breast cancer who had received high-dose chemotherapy with autologous peripheral blood progenitor cell transplantation. Thalidomide was poorly tolerated in this group of patients, and only 20% of the 84 patients could complete the 6-month therapy. Levels of VEGF, not other markers of angiogenesis, were markedly elevated in thalidomide patients when compared to contemporary-treated controls. The increased VEGF levels led the authors postulate the potential role for antiangiogenic therapy in post-transplant patients.

Recently, Baidas et al (J Clin Oncol 48:2710-2717) reported a phase II trial of thalidomide in patients with metastatic breast cancer. Circulating angiogenic factors including basic fibroblast growth factor (bFGF), VEGF, and tumor necrosis factor–alpha (TNF-alpha) were measured. Of 27 patients, 5 (18.5%), 6 (22%), and 13 (48%) had elevated levels of bFGF, VEGF, and TNF-alpha, respectively. Changes in serum bFGF, VEGF, and TNF-alpha levels from baseline to the time of removal from study (either because of progression or toxicity) in 26 patients were determined. The mean percentage changes from baseline were -37% for bFGF, +60% for VEGF, and +79% for TNF-alpha. Circulating levels of TNF-alpha significantly increased in most patients with progression of disease. Interestingly, TNF-alpha levels had decreased in the single patient who experienced a near-partial response. This raises the hypothesis that thalidomide might be active in cancer patients by virtue of decreasing TNF-alpha, or this might be a mere reflection of decreased tumor burden from effective therapy.