Metronomic chemotherapy (MC) in the neoadjuvant setting: Results of two parallel feasibility trials in patients (pts) with HER2 positive (HER2+) and negative (HER2-) locally advanced breast cancer (LABC) (Traq-Me and TAME).

2012 ◽  
Vol 30 (27_suppl) ◽  
pp. 197-197
Author(s):  
Vanessa Petry ◽  
Alessandro Leal ◽  
Roberto J. Arai ◽  
Simone Marinho ◽  
Marcelo Paiva ◽  
...  
Keyword(s):  
Locally Advanced Breast Cancer ◽  
Locally Advanced ◽  
Pathologic Complete Response ◽  
Metronomic Chemotherapy ◽  
Complete Response ◽  
Cardiac Safety ◽  
Her2 Positive ◽  
Negative Results ◽  
Vegf Pathway ◽  
Almost All

197 Background: In a previous randomized trial (SWOG 0012), MC seemed to improve pCR rates compared to standard anthracycline/taxane neoadjuvant chemotherapy (NC). We aimed to evaluate the feasibility of MC with a taxane→anthracycline schedule, which has also been shown potentially superior to the reverse sequence [J Clin Oncol 28:15s, 2010 (suppl; abstr 548)]. We also aimed to establish the feasibility of MC in combination with trastuzumab. Methods: The original accrual goal was 25 HER2+ pts and 40 HER2- pts. HER2- pts received MC consisting of paclitaxel (100mg/m2) x8 weeks followed by doxorubicin (24mg/m2) x9 weeks combined with oral cyclophosphamide (100mg/day), without G-CSF. HER2+ pts also received trastuzumab (4 mg/kg followed by 2mg/kg) concurrently with the entire CT. Objectives: Primary: To evaluate the feasibility of these schedules (defined as a febrile neutropenia [FN] rate no higher than 10%). Secondary: cardiac safety and general tolerability; efficacy as measured by objective clinical, radiological and pathologic complete response (pCR). Results: Almost all pts were staged as III (TraQme 8/9 88% and MeTo 4/11 36%). The HER2+ cohort was prematurely closed after 2 (22%) pts developed G3 pneumonitis (during the metromonic phase). Both responded to medical treatment and recovered. One pt had G2 hand-foot skin reaction (HFS) and another had G2 mucositis. The HER2- cohort was also prematurely closed with only 11 pts because of high rates of mucocutaneous toxicity (G3 HFS in 36%, G3 rash in 9%) and also due to the recent SWOG0221 negative results. There were 2 (18%) cases of FN and 3 (27%) of G4 neutropenia in this cohort, but no cases of pneumonitis. 1/11(9%) HER2- and 5/9HER2+(55%) pts had a pCR. VEGF pathway-related biomarkers were collected and will be presented at a later date. Conclusions: The proposed MC schedules proved too toxic to be considered for further clinical development. In addition, MC resulted in unexpectedly high rates of severe pulmonary toxicity when given in combination with trastuzumab. HER2+ but not HER2- pts had an impressively high pCR rate.

Metronomic chemotherapy (MC): Results of two feasibility trials in patients (pts) with HER2 positive (HER2+) and negative (HER2-) locally advanced breast cancer (LABC).

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. e11513-e11513
Author(s):  
Vanessa Petry ◽  
Alessandro Leal ◽  
Roberto J. Arai ◽  
Jose R. Piato ◽  
Felipe Andrade ◽  
...  
Keyword(s):  
Locally Advanced Breast Cancer ◽  
Phase 1 ◽  
Objective Response ◽  
Locally Advanced ◽  
Pathologic Complete Response ◽  
Metronomic Chemotherapy ◽  
Complete Response ◽  
Primary Objective ◽  
Her2 Positive ◽  
Negative Results

e11513 Background: In SWOG0012, MC improved pathologic complete response (pCR) compared to standard neoadjuvant chemotherapy (NC). We evaluated the feasibility of MC with a taxane→anthracycline schedule, which has also been shown potentially superior to the inverse sequence. We also evaluated the feasibility of MC in combination with trastuzumab. Methods: The primary objective was feasibility (defined as a febrile neutropenia (FN) rate ≤10%). Secondary objectives were cardiac safety, tolerability and efficacy as measured by objective response and pCR. The original accrual goal was 25 Her2+ pts and 40 Her2- pts. Her2- pts received paclitaxel (100mg/m2) x8 weeks followed by doxorubicin (24mg/m2) x9 weeks combined with oral cyclophosphamide (100mg/day), without G-CSF. Her2+ pts also received weekly trastuzumab (4 mg/kg followed by 2mg/kg) concurrently with the entire CT. Results: Most pts were stage III (Her+: 8/9; Her-: 4/11). The Her2+ cohort was prematurely closed after 2(22%) pts developed G3 pneumonitis (both during the MC phase). Both recovered completely. There was 1 case of asymptomatic LVEF drop to below 50% (during the taxane phase); 1 pt had G2 hand-foot skin reaction (HFS) and another had G2 mucositis. The Her2- cohort was also prematurely closed with only 11 pts due to high rates of mucocutaneous toxicity (G3 HFS in 36%, G3 rash in 9%) and also because of SWOG0221 negative results. There were 2(18%) cases of FN, but no cases of pneumonitis. 1/11(9%) Her2- and 5/9(55%) Her2 + pts had a pCR. VEGF-related biomarkers were collected and will be presented at a later date. Conclusions: The proposed MC schedules proved too toxic to be considered for further clinical development. In addition, MC resulted in unexpectedly high rates of severe pulmonary toxicity when given in combination with trastuzumab. Her2+ but not Her2- pts had an impressively high pCR rate.

Phase II open clinical trial to evaluate efficacy and safety of neoadjuvant trastuzumab in HER2-positive locally advanced breast cancer (LABC)

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. 592-592
Author(s):  
C. H. Arce-Salinas ◽  
F. U. Lara ◽  
E. Leon
Keyword(s):  
Breast Cancer ◽  
Locally Advanced Breast Cancer ◽  
Locally Advanced ◽  
Pathologic Complete Response ◽  
Disease Free Survival ◽  
Complete Response ◽  
Her2 Positive ◽  
Primary Systemic Therapy ◽  
Her 2 ◽  
Grade 3

592 Background: LABC in Mexico represents between 50–60% of the new diagnosed cases, and 25–30% of those cancers are HER-2/neu positive. Primary systemic therapy trastuzumab-based combination chemotherapy (ChT) has shown clinical benefit and pathologic complete response rates are obtained between 17%-67%. The aim of this study was evaluate the complete pathologic response (pR) rate with the combination of four cyles of FAC (5FU/Doxorubicin/Cyclophosphamide) followed by weekly paclitaxel (PTX) and trastuzumab. As secondary endpoint was evaluate cardiac safety. Methods: All patients with LABC HER-2 positive (IHC 3+ or FISH amplification) with stages IIb-IIIc were included, patients with palpable nodes underwent fine needle aspiration to confirm metastatic nodal disease (MND), other inclusion criteria was FEVI ≥55% determined by MUGA, hematologic, renal and hepatic function normal. We exclude inflammatory breast cancer. All patients received 4 cycles of FAC followed by weekly PTX (80 mg/m2) concomitantly with trastuzumab, 2 mg/kg, at the end of treatment surgery was performed, and pR was evaluable. Complete pR was defined as the absence of tumor cells in breast and axillary nodes. Disease free survival (DFS) was calculated with Kaplan-Meier method. Protocol was approved by local ethical committee. NCT 00533936. Results: We included 92 patients, median age was 48 (27–68) yrs. Median tumor size was 6 (5.4–6.5) cm, 84.9% had MND. Efficacy analysis was made in 71 patients; 21 patients are still under treatment. Overall clinical response was reached in 71% (complete 37% and partial 42%). Eleven patients were considered inoperable (skin affection, larger size > 5 cm or fixed to chest wall and received radiotherapy 50 Gy). Complete pR was reported in 48% of cases. Median follow-up was 17.4 (CI95% 14.9, 17.6) mo and media of DFS was 25.1 (CI95% 23.5, 26.7) mo. We found cardiac toxicity (CT) grade 3 in 1.1%, and grade 2 in 3.2%. Conclusions: Combination of PTX and trastuzumab after 4 cycles of FAC is highly active in terms of complete pR. This scheme was tolerated, with CT grade 3–4 in less than 2%. No significant financial relationships to disclose.

scholarly journals The Prognostic Impact of Body Composition for Locally Advanced Breast Cancer Patients Who Received Neoadjuvant Chemotherapy

Cancers ◽  
2021 ◽  
Vol 13 (4) ◽  
pp. 608
Author(s):  
Toshiaki Iwase ◽  
Aaroh Parikh ◽  
Seyedeh S. Dibaj ◽  
Yu Shen ◽  
Tushaar Vishal Shrimanker ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Body Composition ◽  
Adipose Tissue ◽  
Neoadjuvant Chemotherapy ◽  
Advanced Breast Cancer ◽  
Locally Advanced Breast Cancer ◽  
Locally Advanced ◽  
Pathologic Complete Response ◽  
Complete Response ◽  
Advanced Breast

Our previous study indicated that a high amount of visceral adipose tissue was associated with poor survival outcomes in patients with early breast cancer who received neoadjuvant chemotherapy. However, inconsistency was observed in the prognostic role of body composition in breast cancer treatment outcomes. In the present study, we aimed to validate our previous research by performing a comprehensive body composition analysis in patients with a standardized clinical background. We included 198 patients with stage III breast cancer who underwent neoadjuvant chemotherapy between January 2007 and June 2015. The impact of body composition on pathologic complete response and survival outcomes was determined. Body composition measurements had no significant effect on pathologic complete response. Survival analysis showed a low ratio of total visceral adipose tissue to subcutaneous adipose tissue (V/S ratio ≤ 34) was associated with shorter overall survival. A changepoint method determined that a V/S ratio cutoff of 34 maximized the difference in overall survival. Our study indicated the prognostic effect of body composition measurements in patients with locally advanced breast cancer compared to those with early breast cancer. Further investigation will be needed to clarify the biological mechanism underlying the association of V/S ratio with prognosis in locally advanced breast cancer.

Predictors of pathologic response to preoperative chemotherapy and concurrent radiotherapy for locally advanced breast cancer

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. e11545-e11545
Author(s):  
R. Venkitaraman ◽  
S. G. Ramanan ◽  
K. R. Rajalekshmy ◽  
T. G. Sagar ◽  
V. Shanta
Keyword(s):  
Breast Cancer ◽  
Advanced Breast Cancer ◽  
Locally Advanced Breast Cancer ◽  
Locally Advanced ◽  
Pathologic Complete Response ◽  
Neoadjuvant Chemoradiotherapy ◽  
Complete Response ◽  
Pathologic Response ◽  
Advanced Breast ◽  
Concurrent Radiotherapy

e11545 Background: Combined modality treatment is essential for acheiving optimal results in the management of locally advanced breast cancer (LABC). Neoadjuvant chemoradiotherapy is considered a promising approach for LABC. Pathologic complete response to neoadjuvant treatment for LABC predicts prolonged survival. Aim: To determine the rate of pathologic complete response (pCR) after neoadjuvant chemotherapy and radiotherapy for locally advanced breast cancer and to identify the predictors of pCR. Methods: Female patients with noninflammatory LABC received neo-adjuvant chemotherapy with concurrent radiotherapy, and then underwent mastectomy and axillary clearance. The pathologic response was analysed with respect to the baseline clinical factors and the receptor status on immunohistochemical studies of the initial biopsy specimen. Results: Of the 296 patients included in the study, 286 underwent mastectomy. Ninety-two (31 %) patients achieved a pCR. The significant predictor of a pCR was Oestrogen receptor negative status (p = 0.025), while progesterone receptor negative status (p=0.069 ), HER2 status (p= 0.62), age (p= 0.074), stage (p=0.6), grade (p=0.86), type of chemotherapy (p=0.37) and number of cycles of chemotherapy (p = 0.23) did not predict for pathologic response. Clinical complete response predicted for a pathologic complete response (p=0.0001). Conclusions: Neoadjuvant concurrent chemoradiotherapy results in good pathologic complete response rates in LABC. High pathologic compete response rates are achieved in patients with endocrine receptor negative disease, with neoadjuvant chemoradiotherapy, which might result in improved outcome in this high risk subset of patients. No significant financial relationships to disclose.

Results of the East Carolina Breast Center phase II trial of neoadjuvant metronomic chemotherapy in triple-negative breast cancer (NCT00542191).

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. e11550-e11550
Author(s):  
Stephen Tiley ◽  
Rachel Elizabeth Raab ◽  
Lisa Sheri Bellin ◽  
Jan H. Wong ◽  
Jackie Unger ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Inflammatory Breast Cancer ◽  
Triple Negative ◽  
Locally Advanced ◽  
Pathologic Complete Response ◽  
Metronomic Chemotherapy ◽  
Complete Response ◽  
Weekly Paclitaxel ◽  
Breast Cancers ◽  
Grade 3

e11550 Background: Triple negative (ER negative, PR negative and HER 2 negative) breast cancers (TNBC) lack effective targeted therapy. We sought to determine the benefit of metronomic neoadjuvant chemotherapy utilizing doxorubicin with cyclophosphamide followed by paclitaxel with carboplatin in women with TNBC. Methods: Patients (pts) with TNBC>2cm were eligible (including locally advanced or inflammatory breast cancer). Pretreatment sentinel node biopsy (SLNB) was performed in patients with clinically N0 disease. Treatment consisted of weekly doxorubicin 24 mg/m2 + daily oral cyclophosphamide 60 mg/m2 x 12 weeks followed by weekly paclitaxel 80 mg/m2 + weekly carboplatin AUC 2 x 12 weeks. Granulocyte colony stimulating factor was added for ANC<= 1000. Pts received standard surgery and radiation therapy as indicated. The primary endpoint was pathologic response. Results: Between 2006 and 2011, 17 pts with infiltrating ductal TNBC were enrolled and 15 were analyzed. Age ranged from 25 to 83 (mean age 45yrs), primary tumor size ranged from 2cm to 7cm (mean 3.5cm). Three pts presented with inflammatory breast cancer, 4 had clinical N1 disease and 2 had clinical N0 disease that did not receive SLNB. Six pts underwent SLNB; 3 were pN0 and 3 were pN positive. Two pts came off study due to prolonged neutopenia. Three pts died during therapy-one of MI, one of PE and one had progressive pulmonary disease. No deaths were therapy related. Ten pts completed therapy. One experienced grade 3 (G3) thrombocytopenia, five patients had G4 neutropenia and one developed G3 neuropathy. Ten pts had a clinical complete response (cCR), four had a clinical partial response (cPR) and one progressed on therapy. The rate of pathologic complete response (pCR) was 46.6% (40% pCR, 6.6% CR with foci of DCIS). One patient had a 0.7cm focus of residual invasive carcinoma. Positive nodes were identified in 13.3%-one patient who progressed on therapy and one who experienced a cPR. Conclusions: Neoadjuvant metronomic chemotherapy with weekly doxorubicin plus daily oral cyclophosamide followed by weekly paclitaxel plus carboplatin revealed high rates of pCR with toxicities limited to marrow suppression.

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