A multicenter phase II trial of weekly paclitaxel (wPC) and epirubicin (E) in first line metastatic breast cancer (MBC) and pronostic impact of VEGF level.

CTRC-AACR San Antonio Breast Cancer Symposium: 2008 Abstracts Abstract #6122 Background : wPC and E are effective in the treatment of MBC. The main objective was to determine the efficacy of combined induction with wPC and E followed by consolidation with wPC. Secondary objective were to determine tolerance survivals and characterize antiangiogenic PC activity and predictive values of plasmatic neurotrophic and endothelial factors, in terms of neurotoxicity and efficacy. Methods : patients (pts) with RECIST measurable metastasis were recruited from april 2004 to may 2006 : ages (18-75 y) PS≤2, prior neoadjuvant adjuvant chemotherapy (NA-A CT) was permited if >6 month. 3 cycles [wPC 80 mg/m² (D1, D8, D15, reinduction D28) and epirubicine 100 mg/m² D15], were followed by wPC (no week rest). VEGF, IL6, IL6SR, BDNF were measured in plasma at baseline and C2. Evaluation was performed after 3 induction cycles and every 3 month. A Simon optimal two-stage design was performed with 13 objective responses, allowing to accrue 25 more patients (28 responses expected). Results : 54 patients: median age 58.5 (30-75); 81% had surgery, 53.7% radiotherapy and 40.7% had NA-A CT, 46.3% hormonotherapy. Metastatic sites were nodes (36) lung (36) liver (28) bone (23). 100% PC and 90% E dose were administered at C2 and C3. 49 patients were evaluable for response; 3 patients withdrawn for taxol hypersensitivity, 1 early death (GIII asthenia and dyspnea), 1 investigator's decision. ITT analysis was performed: 33 responses (ORR: 61 %) Median OS was 30 months. During induction, 16 grade III, 27 grade IV and 3 febrile neutropenia were reported. There were 13 serious adverse events. Consolidation was mainly associated with neurotoxicity n=28 (20pts), GIII (n=1; 3.6%) GIV (n=1; 3.6%), astenia n=26 (18pts) ), GIII n=1; 3.8% GIV n=1; 3.8%and onycholysis n=15 (13pts) ), GIII n=2 ; 13.4% GIV n=1; 6.7%. High initial VEGF plasma levels were correlated with poor survival s (PFS, OS) with an univariate cox model (OR=1.954, 95%CI 0.944-4.043, p=0.071 ; HR 4.437, 95%CI 1.731-11.371, p=0.0019). Thresholds were determined. No correlation were observed between neurotoxicity and IL6, IL6SR and BDNF plasma levels. Conclusion : Despite the significant but manageable haematologic toxicity, PC + E showed a high efficacy. VEGF plasma levels are predictive of the outcome and should be tested as antiangiogenic drugs targeting factors.This work was supported in part by BMS. Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 6122.