High-dose chemotherapy with hematopoietic support improves the response rate for patients with metastatic breast cancer. There are many long-term disease-free survivors following high-dose chemotherapy and autologous peripheral blood progenitor cell support, but the majority of patients relapse and die of breast cancer. Efforts to eliminate minimal residual disease posttransplant may further improve the survival of women with poor-prognosis metastatic breast cancer.
Thalidomide(Drug information on thalidomide) (Thalomid) has potent immunomodulatory properties and inhibits angiogenesis through b-FGF. We conducted a pilot trial of 84 patients with metastatic breast cancer who were treated with high-dose cyclophosphamide(Drug information on cyclophosphamide) (Cytoxan, Neosar), cisplatin(Drug information on cisplatin) (Platinol), and carmustine(Drug information on carmustine) (BiCNU, Gliadel), and autologous hematopoietic support. The patients received thalidomide at 100 to 400 mg/d beginning between 2 and 6 weeks posttransplant.
The thalidomide was poorly tolerated, and only 20% of patients could complete 6 months of the drug. The major toxicities were sedation and peripheral neuropathies. There were no grade 4 or 5 toxicities.
We measured serial vascular endothelial growth factor (VEGF) and other markers of angiogenesis. The thalidomide patients had a marked elevation in their VEGF levels posttransplant compared to contemporary-treated controls. The other markers of angiogenesis were unchanged between the thalidomide and control groups.
CONCLUSION: Thalidomide is poorly tolerated in the posttransplant setting for patients with metastatic breast cancer, but the increased VEGF levels may indicate important biological activity, and a role for inhibitors of angiogenesis posttransplant.