Immunotherapy following high-dose chemotherapy (HDCT) and peripheral blood progenitor cell transplantation (PBPCT) in the treatment of high-risk early breast cancer (HREBC) and metastatic breast cancer (MBC).

Abstract

Abstract Abstract #2159 Background: Meta-analyses have shown that HDCT with PBPCT is not superior to standard dose chemotherapy in the treatment of high risk early breast cancer (HREBC) and metastatic breast cancer (MBC). The reason for the limited efficacy is due to failure to eradicate all cancer stem cells, resistant to chemotherapy, and capable to reproduce the tumor in immunodeficient mice. Lymphopenia has been described after HDCT. We have previously shown that low dose inteterleukin 2 (IL-2) and oral 13-cis- retinoic acid (RA) improved lymphocyte (L) count, and decreased vascular endothelial growth factor (VEGF), of patients with advanced tumors having a clinical benefit from chemotherapy. Primary endpoint of this study was to verify if IL-2 and RA, improving L count, and decreasing VEGF after HDCT with PBPCT of patients with advanced breast cancer, reduced angiogenic switch. Secondary endpoints were the evaluation of progression-free survival (PFS) and overall survival (OS).
 Methods: From 02-1998 to 02-2003, 30 patients with HREBC and 18 with MBC were entered into the study. One month after HDCT, patients received, for 1 year, 5 days/week, 3 weeks/month, subcutaneous IL-2 (1.8 x 106 IU daily) plus RA (0.5 mg/kg body weight). Immunotherapy was continued, with intermittent schedules, up to 5 years. Patients with estrogen receptor positive (ER+) tumors received hormonal therapy, while those in premenopause received also a LHRH analogue for 5 years.
 Results: Characteristics of HREBC patients: median age, 48 years (range 34-60); median number of positive axillary nodes, 13 (range-11-27); ER+/ER-: 20/10; characteristics of MBC patients: median age, 46 years (range 28-60); median number of disease sites 1.5, (range-1-4); ER+/ER-: 5/13; Major adverse effects from IL-2 were fever, rash and autoimmune reactions; no treatment-related mortality was seen. After a median follow-up of 61 months, a statistically significant improvement of L and decrease of VEGF were observed for both HREBC and MBC. 5 years PFS and OS rate were, for HREBC 76% and 85%, respectively, for MBC, 22% and 35%, respectively.
 Conclusions: These data show that IL-2 administration after HDCT and PBPCT is feasible, has a moderate toxicity, gives a statistically significant improvement of L a decrease of VEGF, and seems to give an improvement of expected PFS and OS, both in HREBC and MBC. Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 2159.