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
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 (Cytoxan, Neosar), cisplatin (Platinol),
and 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.