Topoisomerase II alpha (TopoIIa) and MAPtau: Potential predictive markers of response in locally advanced breast cancer (LABC) treated with epirubicin and docetaxel (ET) in neoadjuvant setting.

2011 ◽  
Vol 29 (27_suppl) ◽  
pp. 57-57
Author(s):  
A. Cristofano ◽  
A. Inno ◽  
V. Arena ◽  
L. Nicosia ◽  
G. Jocollè ◽  
...  
Keyword(s):  
Neoadjuvant Chemotherapy ◽  
Response Rate ◽  
Pathological Complete Response ◽  
Objective Response ◽  
Locally Advanced ◽  
Breast Conservation ◽  
Complete Response ◽  
Over Expression ◽  
Short Period ◽  
Normal Expression

57 Background: Neoadjuvant chemotherapy can achieve a high objective response rate in patients with LABC. This allows breast conservation surgery in those patients who are initially not suitable for this procedure. The patients who mainly benefit from neoadjuvant chemotherapy are those who achieve a pathological complete response (pCR) with no residual microscopic tumour. This occurs in only 3–16% of patients, who have substantially improved disease-free survival (DFS) and OS compared to those with pathological evidence of residual cancer. In order to identify patients most likely to achieve benefit from neoadjuvant chemotherapy, it would be useful to identify predictors of pCR. ET is a valid doublet therapy in the neoadjuvant setting; Topo-IIa and MAP-Tau are the principal targets of anthracyclines and taxanes, respectively. We evaluated a possible role of the two proteins in predicting a pathological response rate in LABC. Methods: TopoIIa and MAPtau expression was evaluated by immunohistochemistry (IHC) in tumour biopsy from 22 women with LABC treated with ET as neoadjuvant chemotherapy, and protein levels were correlated to the outcome. Results: TopoIIa over-expression was significantly associated with ductal histology (58.3% in ductal carcinoma vs 0% in other hystotypes, p=.038) and hormone receptors (HRs) expression (63.6% in HR+ vs 0% in HR- tumours), whereas no significant correlation was observed with HER2 expression. MAP-tau did not correlate with histology, grading, HRs and HER2 status. Pathological complete response (pCR) rate was higher in tumours with MAPtau low/normal expression compare to those over-expressing the protein (36.4% vs. 14.3%), although not significantly. Pts with TopoIIa over-expression achieved a significantly higher pCR rate than those with a low/normal expression (57.1% vs. 9.1%; p=.047). Data on the RFS are not available because of the short period of follow-up. Conclusions: IHC evaluation of TopoIIa might be useful in identifying pts potentially responsive to neoadjuvant chemotherapy with anthracyclines and taxanes. Data on RFS will be available later.

scholarly journals Efficacy of dose-intensive platinum-containing neoadjuvant chemotherapy in the combination treatment for locally advanced cervical cancer

2019 ◽  
Vol 14 (4) ◽  
pp. 56-64
Author(s):  
O. A. Smirnova ◽  
N. E. Bondarev ◽  
E. A. Ulrikh ◽  
N. A. Mikaya ◽  
A. S. Petrova ◽  
...  
Keyword(s):  
Cervical Cancer ◽  
Neoadjuvant Chemotherapy ◽  
Pathological Complete Response ◽  
Objective Response ◽  
Locally Advanced ◽  
Complete Response ◽  
Small Sample ◽  
Pathological Response ◽  
Advanced Cervical Cancer ◽  
Locally Advanced Cervical Cancer

Objective:to assess the efficacy of dose-intensive platinum-containing neoadjuvant chemotherapy in patients with FIGO stage IB2–IIB locally advanced cervical cancer.Materials and methods.We evaluated the efficacy and toxicity of 3 cycles of intravenous dose-intensive neoadjuvant chemotherapy with either AP regimen (cisplatin 75 mg/m2 and doxorubicin 35 mg/m2) or TP regimen (cisplatin 60 mg/m2 and paclitaxel 60 mg/m2).Results.The study included 105 patients (75 in the AP group and 30 in the TP group) aged between 27 and 63 years (mean age 44 years) with primary verified cervical cancer (T1–2B0–2Nx–0M0). Surgery was performed in 66 patients (88 %) from the AP group and 24 patients (80 %) from the TP group. Six patients (8 %) receiving AP regimen and 1 patient (3.3 %) receiving TP regimen developed disease progression. Four women (2.8 %) from the AP group developed relapses, whereas none of the patients from the TP group had relapses. Dose-intensive chemotherapy did not cause any significant complications at both chemotherapeutic and surgical stages. Our findings suggest that dose-intensive neoadjuvant chemotherapy is an effective method with an objective response rate of 84 % (63 cases) and 56.7 % (17 cases) in groups AP and TP respectively. Fifty-nine patients (78.7 %) receiving AP regimen had pathological response; of them, 7 participants (9.4 %) demonstrated pathological complete response (ypCR). In the TP group, 19 patients (63.3 %) had pathological response and 4 patients (13.4 %) had pathological complete response. Median follow-up time was 16.7 months (range: 3–29 months) in the AP group and 9.1 months (range: 2.8–12.7 months) in the TP group.Conclusion.Dose-intensive neoadjuvant chemotherapy can be considered as an alternative to standard treatment of locally advanced cervical cancer; however, further studies are needed due to the small sample size in this study.

scholarly journals CAIX is a predictor of pathological complete response and is associated with higher survival in locally advanced breast cancer submitted to neoadjuvant chemotherapy

BMC Cancer ◽  
2019 ◽  
Vol 19 (1) ◽  
Author(s):  
Wilson Eduardo Furlan Matos Alves ◽  
Murilo Bonatelli ◽  
Rozany Dufloth ◽  
Lígia Maria Kerr ◽  
Guilherme Freire Angotti Carrara ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Neoadjuvant Chemotherapy ◽  
Advanced Breast Cancer ◽  
Pathological Complete Response ◽  
Locally Advanced Breast Cancer ◽  
Locally Advanced ◽  
Complete Response ◽  
Advanced Breast ◽  
Metabolic Reprogramming ◽  
Caix Expression

Abstract Background Locally advanced breast cancer often undergoes neoadjuvant chemotherapy (NAC), which allows in vivo evaluation of the therapeutic response. The determination of the pathological complete response (pCR) is one way to evaluate the response to neoadjuvant chemotherapy. However, the rate of pCR differs significantly between molecular subtypes and the cause is not yet determined. Recently, the metabolic reprogramming of cancer cells and its implications for tumor growth and dissemination has gained increasing prominence and could contribute to a better understanding of NAC. Thus, this study proposed to evaluate the expression of metabolism-related proteins and its association with pCR and survival rates. Methods The expression of monocarboxylate transporters 1 and 4 (MCT1 and MCT4, respectively), cluster of differentiation 147 (CD147), glucose transporter-1 (GLUT1) and carbonic anhydrase IX (CAIX) was analyzed in 196 locally advanced breast cancer samples prior to NAC. The results were associated with clinical-pathological characteristics, occurrence of pCR, disease-free survival (DFS), disease-specific survival (DSS) and overall survival (OS). Results The occurrence of pCR was higher in the group of patients whith tumors expressing GLUT1 and CAIX than in the group without expression (27.8% versus 13.1%, p = 0.030 and 46.2% versus 13.5%, p = 0.007, respectively). Together with regional lymph nodes staging and mitotic staging, CAIX expression was considered an independent predictor of pCR. In addition, CAIX expression was associated with DFS and DSS (p = 0.005 and p = 0.012, respectively). Conclusions CAIX expression was a predictor of pCR and was associated with higher DFS and DSS in locally advanced breast cancer patients subjected to NAC.

scholarly journals Pooled analysis of 115 patients from updated data of Epitopes-HPV01 and Epitopes-HPV02 studies in first-line advanced anal squamous cell carcinoma

2020 ◽  
Vol 12 ◽  
pp. 175883592097535 ◽  
Author(s):  
Stefano Kim ◽  
Aurélia Meurisse ◽  
Laurie Spehner ◽  
Morgane Stouvenot ◽  
Eric François ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Squamous Cell ◽  
Response Rate ◽  
Objective Response ◽  
Locally Advanced ◽  
Complete Response ◽  
Pooled Analysis ◽  
Term Survival ◽  
Anal Squamous Cell Carcinoma

Aims: The addition of docetaxel to cisplatin and 5-fluorouracil (DCF) has shown promising efficacy in advanced squamous cell carcinoma of the anus (SCCA). Preliminary results of Epitopes-HPV01 study showed a high rate of long-lasting complete response to DCF. The prospective, multicenter, Epitopes-HPV02 trial then confirmed the high efficacy of the modified DCF (mDCF) regimen in terms of complete response rate and long-term survival in metastatic or non-resectable locally advanced recurrent SCCA. Here, we present updated results of the Epitopes-HPV01 and Epitopes-HPV02 studies. Patients & methods: Epitopes-HPV01 is a prospective study performed by the regional cancer network of Franche-Comté, France. Epitopes-HPV02 is a phase II study supported by two French collaborative oncological groups, performed in 25 centers. Both studies included patients with metastatic, or with unresectable local recurrent SCCA, treated with DCF regimen. Results: In Epitopes-HPV01, 51 patients were enrolled between September 2012 and January 2019, and 49 patients were included for analysis; while 69 patients were included between September 2014 and December 2016 in Epitopes-HPV02, and 66 patients for analysis. Pooled analysis of 115 patients showed a median progression-free survival of 12.2 months [95% confidence interval (CI) 10.6–16.1] [11.0 months (9.3–16.0) in -HPV02, and 15.6 months (11.2–34.5) in -HPV01, ( p = 0.06)]. The median overall survival was 39.2 months (26.0–109.1) [36.3 in -HPV02 (25.2–NR), and 61.1 months (21.4–120.0) in -HPV01 ( p = 0.62)]. Objective response rate was 87.7% (90.9% in -HPV02 and 83.3% in -HPV01) with 40.3% of complete response (45.5% in -HPV02 and 33.3% in -HPV01). No differences were observed between standard DCF ( n = 54) and mDCF ( n = 58) in terms of OS ( p = 0.57) and PFS ( p = 0.99). 5-years PFS and OS rates were 24.5% and 44.4%, respectively, in the whole population. No treatment-related death was observed. Conclusion: Updated results of Epitopes-HPV01 and 02 studies, as well as the pooled analysis, confirm mDCF as a standard treatment in patients with advanced SCCA.

Nimotuzumab in combination with preoperative concurrent chemoradiotherapy for locally advanced esophageal squamous cell carcinoma: A prospective trial.

2016 ◽  
Vol 34 (4_suppl) ◽  
pp. 101-101
Author(s):  
Xiaoyuan Wu ◽  
Yongshun Chen ◽  
Yuanyuan Yang ◽  
Daxuan Hao ◽  
Xue Li ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Esophageal Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Concurrent Chemoradiotherapy ◽  
Response Rate ◽  
Pathological Complete Response ◽  
Complete Response Rate ◽  
Locally Advanced ◽  
Complete Response ◽  
Clinical Response Rate

101 Background: Preoperative chemoradiotherapy is an accepted standard treatment for patients with locally advanced esophageal cancer. Nimotuzumab is a monoclonal antihuman EGFR IgG1 antibody that has demonstrated synergistic activity with both radiotherapy and platinum-based chemotherapy in some solid tumors. The aim of this study is to investigate the safety and efficacy of nimotuzumab in combination with preoperative concurrent chemoradiotherapy for locally advanced esophageal squamous cell carcinoma (ESCC). Methods: Previously untreated patients with stage II-III ESCC received nimotuzumab (200mg per week in weeks1-5), paclitaxel(45 mg/m2 per week in weeks 2-5), cisplatin(20 mg/m2 per week in weeks 2-5) and radiotherapy at a total dose of 40 Gy (2.0Gy/d,5 days per week in weeks 2-5). Esophagectomy was performed 4 weeks after the completion of preoperative strategies. Results: Eighteen eligible patients were enrolled. All patients completed the preoperative regimen, and seventeen patients underwent surgery. The clinical response rate was 94.4% (17/18). The most frequent Grade 1/2 toxicities were esophagitis(12/17), leukocytopenia(14/17), nausea/vomiting(8/17) and fatigue(4/17). Grade 3 leukocytopenia was observed in 11.8 % of patients (3/17). The rate of radical resection was 100%, and the pathological complete response rate was 41.2%(7/17). Downstaging occurred in 15/17 (88.2 %) patients by T stage and 8/17 (47.1%) by N stage. The incidences of postoperative anastomotic leak, pulmonary infection, hoarseness and arrhythmia were 11.8%, 11.8%, 5.9%, and 5.9%, respectively. No perioperative deaths occurred in the study. Conclusions: The regimen of nimotuzumab in combination with preoperative concurrent chemoradiotherapy is safe for locally advanced ESCC. The preoperative strategy is able to achieve substantially high clinical response rate and pathological complete response rate.

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