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

November 1, 2000

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

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.