SU5416 is an anti-angiogenic molecule that inhibits VEGF-mediated signaling through Flk-1. This Phase I trial of SU5416 and Adriamycin (ADR) in stage IIIB/IV inflammatory breast cancer examines the toxicity of SU5416 and its in vivo effects via correlative studies performed pre-treatment, after 2 and 5 cycles. 15 patients (pts) have received dose-escalated SU5416 IV/1hr twice weekly for 15 wk, with dose-escalated ADR IVP q21 days for 5 cycles. All pts then undergo modified radical mastectomy (MRM) followed by XRT and TAM for ER/PR+ disease. Preliminary Results: 13 pts had gr 1 headache with the first administration of SU5416; 13 pts had gr 1-2 phlebitis. ADR 75 mg/m2 had 2 DLTs (neutropenia) and none with 60 mg/m2 (MTD). No pts progressed on therapy. Ten pts have undergone MRM. All breast specimens contained diffuse angiolymphatic invasion. Median of 9 lymph nodes were positive (range: 0-25). MR perfusion estimation demonstrated decreased tumor blood flow (Kep=efflux rate constant pre- vs post-Rx F=3.30, P=0.065). VEGF levels increased with therapy (mean: pre- 24.9 pg/ml, post- 41.3 pg/ml, P<0.01); levels of basic fibroblast growth factor (bFGF) varied. Tumor microvessel density (MVD) did not change (mean: pre-32.2, post-19.8, P= 0.106). PK analysis of SU5416 alone, vs SU5416 with ADR yielded a shorter t1/2β: 27.8 vs 19.9 min (P<0.01). This is due to a smaller Vd when ADR is added (16 vs 12.8 L/m2; P=0.04). Conclusions: SU5416 combined with ADR has an acceptable toxicity profile. Treatment is associated with a reduction in MR tumor blood flow and an increase in VEGF levels, but no change in bFGF levels or MVD.
|Original language||English (US)|
|Number of pages||1|
|Journal||Breast Cancer Research and Treatment|
|State||Published - Jan 1 2001|
ASJC Scopus subject areas
- Cancer Research