Khaled Jabboury, Lena Rogers, Krystal Sexton, Odelia Garcia. (2015). Proceedings of American Association for Cancer Research (AACR). Abstract CT127 (Poster presentation).
Can potential curability bereached in high risk/metastatic breast cancer patients with a treatment optimization strategy that includes a novel GNT (gemcitabine, vinorelbine, docetaxel) in front line combination chemotherapy?
Aiming at improving the therapeutic outcome of sequential taxane and anthracycline front line chemotherapy in breast cancer, G and N were incorporated into the taxane arm; GNT x 4 courses (G 1800-2500mg/m², N 20-30mg/m², T 100mg/m², I.V. on day 1. GNT was administered sequentially with L-FAC x 4 courses; 72hr infusion of 400mg/m²/d 5-fluorouracil modulated by I.V. bolus 200mg/m²/d x 3 leucovorin. This was given concomitantly with 24hr d1 I.V. infusion 600mg/m² cyclophosphamide, followed by 48hr I.V. infusion d2 + d3 60mg/m² doxorubicin (ASCO 2006# 10741). Chemotherapy was given in a dose dense pattern with filgrastim support. As data became available, transtuzumab (for 1< year) was incorporated in HER2+ subset (15 patients) as of 11/2004, cis-platin (P) 70mg/m²/d1; GNTP in HER2+ and Triple negative (TN) subsets (20 patients) as of 5/2007 and bevacizumab 5mg/kg/wk I.V. in inflammatory and Stage IV HER2- subsets (6 patients) as of 10/2007. Hormone receptor positive (HOR+) subset (18 patients) received post chemotherapy hormone maintenance. Ten patients also received additional therapies. From 3/2001 to 2/2012, 52 patients (Median age 48) participated including the following stages: I; 3 (6%), II; 24 (46%), III; 17 (33%), IV; 8 (15%). The following subsets were represented; Triple negative 22 (42%), HER2+ 19 (37%), HER2-/HOR+ 11 (21%). Modified Blacks nuclear grade 3 was noted in 71% and Ki67 > 14% in 91%. 83% had breast conservation and 23 (44%) neoadjuvant chemotherapy; 87% achieved major pathologic response (14 PCR, 2 RCB1, 4 PET/CR/negative biopsy) at a median follow up of 75 months (m). Adjuvant chemotherapy follow up was longer at 116 m. At 81 m, 8/8 Stage IV patients achieved complete remission, though 1 patient (HER2+) had successfully treated intracranial relapse and another developed a second breast primary. At an overall follow up of 85 m (29-154), 4 relapses were observed; 2 HER+ (Stage III/without transtuzumab; Stage IV intracranial relapse only), 1 Inflammatory TN without PCR, 1 HOR+ late relapse > 10 year with short hormonal therapy. There were 3 deaths; 2 breast cancer related. Freedom from relapse for TN was 95% at 82 m, HER2+ 89% at 84 m, HER-/HOR+ 91% at 116 m. Dose dense limiting events included thrombocytopenia, muco-cutaneous reactions, and patient desired breaks. Other side effects noted were; decreased cardiac ejection fraction (2), decreased hearing (1), chronic peripheral neuropathy (2), AML (1), and MDS (1). Despite the limited study population number, this treatment approach resulted in high pathologic remission, complete remission in Stage IV and substantial freedom from relapse in high-risk and metastatic breast cancer subsets. This is highly suggestive that the natural history of aggressive breast cancer can be favorably influenced with this treatment approach.