Neoadjuvant Docetaxel Chemotherapy Research Articles

Does resection after neoadjuvant chemotherapy of docetaxel, oxaliplatin, and S-1 (DOS regimen) benefit for gastric cancer patients with single non-curable factor? a multicenter, prospective cohort study (Neo-REGATTA)

BackgroundThe Neo-REGATTA study evaluated the effectiveness and safety of Docetaxel, oxaliplatin, and S-1 (DOS regimen) followed by radical resection vs. chemotherapy in advanced gastric adenocarcinoma patients with single non-curable factor.MethodsThis cohort study prospectively enrolled advanced gastric adenocarcinoma patients with single non-curable factor between November 2017 and June 2021. Patients without progression after four cycles of DOS were divided into resection group and chemotherapy group. The outcomes included overall survival (OS), progression-free survival (PFS) and safety. Effectiveness analysis was also performed by propensity score matching (PSM).ResultsA total of 73 patients were enrolled and 13 patients were withdrawn due to disease progression after 4 cycles of DOS. Afterwards, 35 and 25 participants were in the resection and chemotherapy groups, respectively. After a median follow-up time of 30.0 months, the median PFS and OS were 9.0 months, and 18.0 months for the chemotherapy group, but not reached in the resection group. After PSM, 19 matched participants were in each group, and the median PFS and OS were longer in resection group than that in chemotherapy group. The most common grade 3 or 4 adverse events both in the resection group and chemotherapy groups were neutropenia (5.7%, 8.0%) and leukopenia (5.7%, 8.0%).ConclusionsRadical resection might provide survival benefit compared with continuous chemotherapy alone in advanced gastric adenocarcinoma patients who had a disease control after DOS, with a good safety profile.Trial registrationThe study protocol was registered on ClinicalTrial.gov (NCT03001726, 23/12/2016).

Pathological outcomes of HER2-positive early breast cancer patients treated with neoadjuvant trastuzumab or dual anti-HER2 therapy and carboplatin with docetaxel: A Maria Sklodowska-Curie National Research Institute of Oncology experience.

e12655 Background: Pathological complete response (pCR) after neoadjuvant chemotherapy (NACT) for breast cancer predicts the risk of recurrence and increasingly may indicate the need for additional therapy postoperatively. Methods: A retrospective analysis was performed in two cohorts of patients (pts) treated with docetaxel, trastuzumab and carboplatin (TCH) or with docetaxel, carboplatin and dual blockade (TCH-P) in the neoadjuvant setting in patients with early breast cancer (tumor size < 50 mm and > 10 mm and cN0 or cN1) in our Clinic, and who had definitive surgery was conducted. Demographic data, size, grade, tumor type, receptor status prior to neoadjuvant treatment, pathological complete response (pCR) rates, and adverse effects were analyzed. The pCR was defined as ypT0 ypN0. Results: Patient in cohort A (n = 58) received TCH x 6 cycles and in cohort B (n = 25) TCH-P x 6 cycles. Median age was 51 (range 23 to 76 years) in cohort A and 46 (range: 30-68) in cohort B. In cohort A 37 (64%) of pts was HR-positive, in cohort B only 9 (36%) pts . The most common adverse events in both groups were neutropenia, diarrhea, chemotherapy induced polyneuropathy and febrile neutropenia. There are no significant differences in the frequency of adverse events in two cohorts. There was no symptomatic heart failure, but 6 pts (10%) in cohort A and 5 pts (16%) in cohort B had > 10% asymptomatic decrease in LVEF. All patients were evaluable for pCR. Higher rates of pCR were achieved in the HER2pos/HRneg pts: 66% (n = 14) in cohort A, and 87% (n = 14) in cohort B. In group HER2pos/HRpos pts, the pCR rate was 48% (n = 18) vs 55% (n = 5) respectively. Conclusions: In HER2positive early breast cancer, a dual blockade (trastuzumab and pertuzumab) together with carboplatin and docetaxel neoadjuvant chemotherapy achieved higher rates of pCR ( 76%) compared with pts treated with trastuzumab, carboplatin and docetaxel (56%). However, a much higher percentage of pCR was observed in the group of patients with non-luminal cancers, who received a double blockade (87% vs 66%).

Abstract P2-16-03: Neoadjuvant treatment of triple negative breast cancer patients with docetaxel and carboplatin to assess anti-tumor activity

Abstract Background: Anthracycline- and taxane-based neoadjuvant chemotherapy (NAT) in triple negative breast cancer (TNBC) patients yields a pathological complete response (pCR) rate of approximately 45%. Anthracyclines can lead to long-term toxicities including congestive heart failure and leukemia. TNBC patients achieving pCR have excellent long-term outcomes irrespective of NAT regimen. This study was designed to evaluate the efficacy of a non-anthracycline NAT regimen with carboplatin and docetaxel in TNBC. Correlative studies include detecting and tracking plasma circulating tumor DNA (ctDNA) to determine if it will predict clinical outcomes, and whole exome sequencing (WES) on tissue samples to decipher the genomic architecture of those who achieve pCR versus those who do not. Methods: This is a joint analysis of two identical multicenter trials. Eligible patients with AJCC 7 clinical stages II and III TNBC received docetaxel 75mg/m2 and carboplatin AUC 6 every 3 weeks X 6 cycles. Following NAT, all patients underwent definitive surgery. The primary endpoint is pCR (no invasive tumor in the breast and axilla). Secondary objectives include evaluating ctDNA as a prognostic biomarker that may be used in identifying TNBC patients at a high risk of disease relapse, and evaluating differences in the genomic architecture between pCR and non-pCR patients. Patients have a research biopsy at baseline, cycle 1 day 3 (optional), and at definitive surgery for those with residual disease. Plasma for ctDNA is collected at baseline, cycle 1 day 3, at definitive surgery, and every 6 months for 5 years. Results: Between 2014 and 2019, 103 patients have been registered. Median age is 53 years (range 25-74), 27.2%: African-American, 77.7%: clinical stage II. Ninety-nine have completed NAT and have had surgery. In the intent to treat population, the preliminary pCR rate is 46.5% (95% CI 36.9% - 56.2%). Nine (8.7%) have developed recurrent disease, and 7 (6.8%) have died. Preliminary ctDNA results from 6 patients (4 non-pCR, 2 pCR) show that ctDNA is detectable in 67%. We identified 627 somatic variants by exome analysis. Of these, 10 variants overlapped with the Swift panel (Accel-Amplicon™ 56G Oncology Panel v2) used for ctDNA sequencing and variant detection. TP53 variants were identified in all 6 patients’ tumor tissue samples. At least one TP53 variant was identified in 4 patients’ baseline pre-chemotherapy ctDNA. Both pCR patients had either no detectable ctDNA TP53 mutations, or clearance of ctDNA following chemotherapy. Three non-PCR patients had persistent TP53 mutations in ctDNA during the treatment course. WES and ctDNA analysis on all patients is currently ongoing. Conclusions: We report a very encouraging pCR rate of 46.5% in TNBC patients with carboplatin and docetaxel NAT. This rate is similar to observed rates with anthracycline- and taxane-based NAT and may represent an option for treatment for TNBC patients. Correlative genomic and ctDNA studies are ongoing. Clinical trial information: NCT02124902 & NCT02547987. Citation Format: FOLUSO O ADEMUYIWA, Mothaffar F Rimawi, Tracy Summa, Jingqin Luo, Tao Wang, Rama Suresh, Lindsay Peterson, Michael Naughton, Ashley Frith, Leonel Hernandez-Aya, Katherine Weilbaecher, Cynthia Ma, Aadel A Chaudhuri, Yang-Yang Feng, Zachary L Skidmore, Obi L Griffith, Malachi Griffith, Matthew Ellis. Neoadjuvant treatment of triple negative breast cancer patients with docetaxel and carboplatin to assess anti-tumor activity [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P2-16-03.

Over-expression of FSIP1 promotes breast cancer progression and confers resistance to docetaxel via MRP1 stabilization

Fibrous sheath-interacting protein 1 (FSIP1) functions centrally in breast carcinogenesis and progression, although its exact role remains to be clarified. Therefore, we sought to establish a correlation between the clinico-pathological features of breast cancer and FSIP1 expression in breast cancer tissues, as well as to validate its role in tumor progression and chemo-resistance. We analyzed FSIP1 expression in the breast cancer and para-tumor tissues by immunohistochemistry. We performed MTT, Caspase-Glo 3/7 Assay, Annexin V staining, wound healing and trans-well assays to evaluate cellular apoptosis, proliferation, migration and invasion in FSIP1 knockout and wild-type breast cancer cell lines. Additionally, we examined the effects of FSIP1 on docetaxel sensitivity in a nude mice model transplanted with control or FSIP1 knockout breast cancer cells, and also evaluate its role in tumor metastasis. FSIP1 and MRP1 interaction was determined by co-immunoprecipitation and mass spectrometry. We found that breast cancer cells and tissues consistently demonstrated elevated FSIP1 expressions, which correlated with poor overall survival. Notably, patients with high FSIP1 expression in their tumors undergoing docetaxel neoadjuvant chemotherapy had shorter disease-free survival. FSIP1 knockout in breast cancer cells significantly increased their sensitivity to docetaxel both in vitro and in vivo. Mechanistically, FSIP1 bound to the multidrug resistance protein 1 (MRP1) and stabilized it, and knocking out FSIP1 decreased MRP1 expression and increased cellular docetaxel accumulation. In sum, FSIP1 promotes breast carcinogenesis and mediates docetaxel resistance, and may serve as a novel target in the development of breast cancer therapies.

Pathological Response and Survival in Triple-Negative Breast Cancer Following Neoadjuvant Carboplatin plus Docetaxel.

Prognostic value of pathologic complete response (pCR) and extent of pathologic response attained with anthracycline-free platinum plus taxane neoadjuvant chemotherapy (NAC) in triple-negative breast cancer (TNBC) is unknown. We report recurrence-free survival (RFS) and overall survival (OS) according to degree of pathologic response in patients treated with carboplatin plus docetaxel NAC. One-hundred and ninety patients with stage I-III TNBC were treated with neoadjuvant carboplatin (AUC6) plus docetaxel (75 mg/m2) every 21 days × 6 cycles. pCR (no evidence of invasive tumor in breast and axilla) and Residual cancer burden (RCB) were evaluated. Patients were followed for recurrence and survival. Extent of pathologic response was associated with RFS and OS using the Kaplan-Meier method. Median age was 51 years, and 52% were node-positive. pCR and RCB I rates were 55% and 13%, respectively. Five percent of pCR patients, 0% of RCB I patients, and 58% of RCB II/III patients received adjuvant anthracyclines. Three-year RFS and OS were 79% and 87%, respectively. Three-year RFS was 90% in patients with pCR and 66% in those without pCR [HR = 0.30; 95% confidence interval (CI), 0.14-0.62; P = 0.0001]. Three-year OS was 94% in patients with pCR and 79% in those without pCR (HR = 0.25; 95% CI, 0.10-0.63; P = 0.001). Patients with RCB I demonstrated 3-year RFS (93%) and OS (100%) similar to those with pCR. On multivariable analysis, higher tumor stage, node positivity, and RCB II/III were associated with worse RFS. Neoadjuvant carboplatin plus docetaxel yields encouraging efficacy in TNBC. Patients achieving pCR or RCB I with this regimen demonstrate excellent 3-year RFS and OS without adjuvant anthracycline.

11C]Choline PET/CT in therapy response assessment of a neoadjuvant therapy in locally advanced and high risk prostate cancer before radical prostatectomy

PurposeRecent studies have shown promising results of neoadjuvant therapy in prostate cancer (PC). The aim of this study was to evaluate the potential of [11C]Choline PET/CT in therapy response monitoring after combined neoadjuvant docetaxel chemotherapy and complete androgen blockade in locally advanced and high risk PC patients.ResultsIn [11C]Choline PET/CT there was a significant decrease of SUVmax and SUVmean (p = 0.004, each), prostate volume (p = 0.005) and PSA value (p = 0.003) after combined neoadjuvant therapy. MRI showed a significant prostate and tumor volume reduction (p = 0.003 and 0.005, respectively). Number of apoptotic cells was significantly higher in prostatectomy specimens of the therapy group compared to pretherapeutic biopsies and the control group (p = 0.02 and 0.003, respectively).Methods11 patients received two [11C]Choline PET/CT and MRI scans before and after combined neoadjuvant therapy followed by radical prostatectomy and pelvic lymph node dissection. [11C]Choline uptake, prostate and tumor volume, PSA value (before/after neoadjuvant therapy) and apoptosis (of pretherapeutic biopsy/posttherapeutic prostatectomy specimens of the therapy group and prostatectomy specimens of a matched control group without neoadjuvant therapy) were assessed and tested for differences and correlation using SPSS.ConclusionsThe results showing a decrease in choline uptake after combined neoadjuvant therapy (paralleled by regressive and apoptotic changes in histopathology) confirm the potential of [11C]Choline PET/CT to monitor effects of neoadjuvant therapy in locally advanced and high risk PC patients. Further studies are recommended to evaluate its use during the course of neoadjuvant therapy for early response assessment.

Association between the expression of IGF1R and estrogen receptor and efficacy of neoadjuvant chemotherapy in beast cancer patients

To detect the expression of IGF1R and estrogen receptor, and to explore the relationship between their expression and the pathological complete response (pCR) rate of neoadjuvant chemotherapy (docetaxel plus epirubicin) in breast cancer patients. We selected 139 women with breast cancer who underwent neoadjuvant chemotherapy (docetaxel plus epirubicin), and detected the expression of IGF1R and estrogen receptor in the samples taken before chemotherapy by Immunohistochemistry. The association between their expression and pCR rate of neoadjuvant chemotherapy was analyzed. Among the 139 cases, IGF1R was highly expressed in 45.3% (63/139) cases, and ER was positively expressed in 62.6% (87/139) cases. IGF1R was highly expressed in 54.0% (47/87) of the ER+ cases, significantly higher than that of ER- cases (30.8%, P<0.01). The overall pCR rate of all the 139 patients who received docetaxel plus epirubicin as neoadjuvant chemotherapy was 10.1% (14/139). The pCR rate was 19.2% (10/52) of the ER- patients and 4.6% (4/87) of the ER+ patients (P<0.05). The pCR rate was 10.5% (8/76) in the patients with low IGF1R expression and 9.5% (6/63) in the patients with high IGF1R expression (P>0.05). The patients with negative expression of ER and high expression of IGF1R showed the highest pCR rate (31.2%, P<0.01). Breast cancer patients with negative expression of ER and high expression of IGF1R are more sensitive to neoadjuvant chemotherapy of docetaxel plus epirubicin, and their pCR rate is significantly higher than that of other patients.

MP82-18 EFFECT OF NEOADJUVANT DOCETAXEL CHEMOTHERAPY COMBINED WITH ADJUVANT CHEMOTHERAPY COMPARED WITH RADICAL PROSTATECTOMY ALONE IN PATIENTS WITH HIGH RISK PROSTATE CANCER

You have accessJournal of UrologyProstate Cancer: Advanced II1 Apr 2015MP82-18 EFFECT OF NEOADJUVANT DOCETAXEL CHEMOTHERAPY COMBINED WITH ADJUVANT CHEMOTHERAPY COMPARED WITH RADICAL PROSTATECTOMY ALONE IN PATIENTS WITH HIGH RISK PROSTATE CANCER Wansuk Kim, Cheryn Song, and Hanjong Ahn Wansuk KimWansuk Kim More articles by this author , Cheryn SongCheryn Song More articles by this author , and Hanjong AhnHanjong Ahn More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2015.02.537AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Preoperative chemotherapy with androgen deprivation therapy is under investigation, some with promising results. However, the definitive value of preoperative and postoperative chemotherapy-only therapy remains unevaluated for high risk prostate cancer. We investigated the efficacy of docetaxel treatment before and after radical prostatectomy (RP) in patients with high risk prostate cancer. METHODS Patients with high risk prostate cancer according to D'Amico criteria were prospectively randomized to one of two treatment groups: neoadjuvant chemotherapy (three cycles) followed by RP (arm A, n=27); or RP alone (arm B, n=21). Patients in arm A were treated with 75 mg/m2 IV docetaxel every three weeks following premedication with 8 mg of dexamethasone; they then underwent RP two weeks later. After RP, 17 patients in group A were treated with docetaxel with same schedule. The median observation time was 50.74 months in both arms. RESULTS There were no differences in the age (66.6 and 64.2 years, p=0.080), pretreatment PSA levels (23.9 and 16.2 ng/mL, p=0.052), clinical stage and Gleason score between the patients in arm A and B, respectively. Grade 1-2 non-hematologic toxicities occurred in 13 patients (81.3%), none with grade 3-4 toxicities. The pathological stages were: T2 in 4(23.5%), T3a in 8(47.1%), and T3b in 5 (29.4%) in arm A; T2 in 5(23.8%), T3a in 8(38.1%), and T3b in 8(38.1%) in arm B (p=0.914). Positive margin rate was similar between the arms in pT2 patients while in pT3 patients it was lower in arm A (37.5% vs. 90.9%, p=0.008). PSA response (> 25% reduction) after chemotherapy was observed in 8 patients (50.0%), but pathological downstaging was noted in 2 (12.5%). After RP, 6 and 7 from each group failed to reach undetectable PSA. PSA failure rate was 27.3%, 50.0% in arm A and B respectively (p=0.414). CONCLUSIONS Docetaxel neoadjuvant chemotherapy lowers positive resection margin in patients with high risk prostate cancer. However, pathological downstaging or immediate oncological result was observed only in a limited number of patients who demonstrated substantial PSA response. But there was no difference in biochemical recurrence free survival. © 2015 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 193Issue 4SApril 2015Page: e1044 Advertisement Copyright & Permissions© 2015 by American Urological Association Education and Research, Inc.MetricsAuthor Information Wansuk Kim More articles by this author Cheryn Song More articles by this author Hanjong Ahn More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...

Long-term survival of patients with locally advanced prostate cancer managed with neoadjuvant docetaxel and radical prostatectomy

BackgroundPatients with locally advanced prostate cancer (PCa) have worse outcomes after radical prostatectomy (RP) than patients with more favorable parameters. We conducted a phase II study of neoadjuvant chemotherapy with docetaxel before RP during 2000 to 2003 in patients with locally advanced disease. We report an updated long-term survival analysis of these patients. Material and methodsOverall, 28 patients with locally advanced PCa (defined as serum preoperative [initial] prostate-specific antigen level≥15ng/ml, clinical≥T2b disease, or biopsy Gleason score ≥8) and no evidence of metastatic disease received 6 weekly doses of intravenous docetaxel (40mg/m2) followed by RP. Disease status was assessed by shared medical records or followed by phone and fax. Biochemical recurrence (BCR) was defined as 2 consecutive prostate-specific antigen level readings≥0.2ng/ml. A Social Security Death Index search was conducted on all patients to ascertain date of death if unavailable in records. ResultsIn total, 28 patients completed chemotherapy and underwent RP. At a median follow-up of 130 months (range: 37–166mo), 10 patients (36%) remained alive and disease free clinically and biochemically with no additional therapy, whereas 18 patients (64%) had BCR. The estimated 10-year BCR-free survival is 33.5%, metastasis-free survival is 68.7%, PCa-specific survival is 92.2%, and overall survival is 79.7%. ConclusionsThe use of neoadjuvant docetaxel chemotherapy in patients with locally advanced PCa undergoing RP remains undefined. Results from this study are informative but only hypothesis generating given the study was not powered for survival. Mature data from the ongoing CALGB 90203 and GETUG-12 studies will shed light on this clinical question.

P075 Is neoadjuvant docetaxel chemotherapy and androgen blockage before curative treatment feasible in locally advanced high-risk prostate cancer?

P075 Is neoadjuvant docetaxel chemotherapy and androgen blockage before curative treatment feasible in locally advanced high-risk prostate cancer?

B59 - Safety, objective response rate and long-term oncologic outcomes of docetaxel neoadjuvant chemotherapy followed by radical prostatectomy for patients with intermediate- and high-risk prostate cancer: a retrospective singlecenter study

B59 - Safety, objective response rate and long-term oncologic outcomes of docetaxel neoadjuvant chemotherapy followed by radical prostatectomy for patients with intermediate- and high-risk prostate cancer: a retrospective singlecenter study

Long-term results of a phase II study with neoadjuvant docetaxel chemotherapy and complete androgen blockade in locally advanced and high-risk prostate cancer

BackgroundPatients with locally advanced and high-risk prostate cancer (LAPC) are prone to experience biochemical recurrence despite radical prostatectomy (RP). We evaluated feasibility, safety and activity of a neoadjuvant chemohormonal therapy (NCHT) with 3-weekly full dose docetaxel and complete androgen blockade (CAB) in locally advanced and high-risk prostate cancer patients (LAPC) undergoing RP.MethodsPatients (n = 30) were selected by Kattans’ preoperative score and received trimestral buserelin 9,45 mg, bicalutamide 50 mg/day and 3 cycles docetaxel (75 mg/m2) followed by RP. Primary endpoints were biochemical (PSA) and local downstaging. Secondary endpoints included toxicity and operability assessments, pathological complete response (pCR), time to PSA progression, 5-year biochemical recurrence free survival (bRFS) and overall survival (OS).ResultsMedian baseline PSA was 25.8 ng/ml (2.1–293), and the predicted probability of 5-year bRFS was 10% (0–55). NCHT induced PSA-reduction was 97.3% (81.3-99.9%; p < 0.001) and post-RP 96.7% of patients were therapy responders, with undetectable PSA-values. Post- vs. pretreatment MRI indicated a median tumor volume reduction of 46.4% (−31.3-82.8; p < 0.001). A pathological downstaging was observed in 48.3%. Severe hematologic toxicities (≥CTC3) were frequent with 53.8% leucopenia, 90% neutropenia and 13.3% febrile neutropenia. RP was performed in all patients. While resectability was hindered in 26.7%, continence was achieved in 96.7%. Pathologic analyses revealed no pCR. Lymph node- and extracapsular involvement was observed in 36.7% and 56.7% with 33.3% positive surgical margins. After a median of 48.6 (19.9-87.8) months, 55.2% of therapy responders experienced PSA-recurrence. The estimated median time to PSA-progression was 38.6 months (95%CI 30.9-46.4) and 85.3 months (95%CI 39.3–131.3) for OS. The 5-year bRFS was improved to 40%, but limiting for interpretation adjuvant treatment was individualized.ConclusionsNCHT is feasible despite high hematotoxicity, with excellent functional results. Significant downstaging was observed without pCR. NCHT seems to improve the cohort adjusted 5-year bRFS, but clinical value needs further investigation in randomized trials.

PIK3CA mutations are a predictor of docetaxel plus epirubicin neoadjuvant chemotherapy clinical efficacy in breast cancer.

This study proposed to investigate the relationship of PIK3CA somatic mutations, the most common activating mutations in human breast cancer (BC), and the efficacy of neoadjuvant chemotherapy (NCT).Using a novel liquid chip technology,PIK3CA DNA somatic mutations and HER2, PTEN, EGFR mRNA expression profiles were analyzed in formalin fixed paraffin embedded samples of 93 BC patients treated with epirubicin plus docetaxel NCT.PIK3CA mutations were found in 30 patients (32.3%), in which the point mutations of E542K, E545K, H1047L and H1047R were 4.3, 9.7, 4.3 and 14.0%respectively. The PIK3CA mutations were significantly associated with patients' clinical response; 27 of 30 PIK3CA mutated patients had either a partial or complete response (p=0.002). Multivariate analysis further confirmed that, after adjustments for age, disease stages and NCT cycles, PIK3CA was associated with clinical response (Odds Ration 0.126, 95% CI [0.029,0.691]). However, there was no significant difference between PIK3CA mutations in pathological complete response (pCR,7 /92) and non-pCR group. Furthermore, no EGFR, KRAS and BRAF mutations were detected in any of the 93 samples. Our data for the first time suggested that PIK3CA mutation status may be a predictor for better understanding clinical response to the combination of epirubicin and docetaxel NCT in patients with BC.

PIK3CA as a predictor of the clinical efficacy for epirubicin plus docetaxel neoadjuvant chemotherapy in breast cancer.

113 Background: PIK3CAgene mutations are the most common activating mutations in human breast cancer (BC). Its association with the resistance to herceptin in HER2-positive BC was reported, but whether it’s related to the efficacy of neoadjuvant chemotherapy is unknown. Methods: We reviewed records of 108 patients with BC treated with epirubicin plus docetaxel neoadjuvant chemotherapy between June 2005 and April 2011. 92 patients’ clinical and pathologic objective response data were collected. FFPE tumor biopsies obtained at the time of diagnoses (and before treatment) were collected. EGFR, KRAS, BRAF, PIK3CA mutations and HER2, PTEN, EGFR mRNA expression were analyzed by liquidchip technology. Chi-square test and Fisher’s exact test were used in statistical analysis. A p value less than 0.05 was considered statistically significant. Results: No mutation was detected in EGFR, KRAS and BRAF. The mutation rate of PIK3CA was 35.1% (38/108), and mutation rates of E542K, E545K, H1047L and H1047R were 3.7, 10.2, 3.7 and 17.6% respectively. More PIK3CA mutations were detected in HER2 high expression tumors (p=0.018). No correlation was found between PIK3CA mutations and PTEN, EGFR expression. Clinical response (CR+PR, 63/92) was associated with PIK3CA mutations (p=0.002). However, PIK3CA mutations rate between pathologic complete release (pCR, 7/92) and non-pCR group was not significantly different (p=0.422). Conclusions: PIK3CA mutation may predict better clinical response in BC patients treated with epirubicin plus docetaxel neoadjuvant chemotherapy. More studies are needed to validate these results and the correlation between PIK3CA mutations and pCR.

Neoadjuvant chemotherapy of docetaxel and carboplatin in patients with stage Ib2 to IIb nonsquamous cervix cancer of the uterus.

5103 Background: Non-squamous carcinoma of the uterine cervix has a resistance to radiation therapy and chemotherapy, and this is associated with worse prognosis compared with squamous carcinoma. This is a phase II study to assess an efficacy and safety of neoadjuvant chemotherapy of docetaxel and carboplatin (DC therapy) in patients with stage Ib2 to II non-squamous cervix cancer of the uterus. Methods: Patients with histologically confirmed, stage Ib2-II non-squamous uterine cervix cancer were received DC therapy prior to type III radical hysterectomy. IV doceaxel was administered at 60 mg/m2 followed by IV carboplatin administration based on AUC=6. The treatment was repeated every 21 days for a total of 1 to 3 cycles. Surgery was performed as soon as sufficient response was obtained. Results: Fifty-three women with non-squamous cervical carcinoma (FIGO stage Ib2,15; IIa, 7; IIb, 31) received DC therapy. Median age and tumor size were 49 years old (range: 27-71) and 52mm (range: 10-92), respectively. Fourty of 47 patients (74%) received 2 cycles of chemotherapy. Clinical response occurred in 69.8% of patients (complete response, 5; partial response, 32; stable disease, 15; disease progression, 1), and 96% (52/54) of patients completed the surgery. Incidences of grade 3/4 hematological toxicities were 98% (53/54) for neutrocytopenia, 4% (2/54) for thrombocytopenia, and 9% (5/54) for anemia. Febrile neutropenia was observed in three patients. Observed grade 3/4 non-hematological toxicities included were 5 for nausea, 2 for vomiting, 3 for constipation, 4 for allergic reaction. Median follow-up duration was 860 days with a range of 147- 1635 days. The 2-years progression-free survival rate and 2-years overall survival rate were 63% and 79% in stage IB2, 71% and 86% in stage IIA2, and 67% and 86% in stage IIB, respectively.Twenty patients recurred and twelve patients died. Conclusions: Neoadjuvant chemotherapy using DC therapy was well tolerated and had good response. It seems to be benefical in patients with satge Ib2 to II nonsquamous cervical cancer.

Comparison of Doxorubicin Plus Docetaxel Neoadjuvant Chemotherapy with Doxorubicin Plus Vinorelbine in Primary Breast Cancer

PurposeThis study was performed to compare the therapeutic efficacy and toxicity of doxorubicin plus docetaxel neoadjuvant chemotherapy (NC) with doxorubicin plus vinorelbine NC.MethodsFifty-three patients underwent 4 cycles of NC consisted of intravenous injection of doxorubicin (50 mg/m2) plus docetaxel (75 mg/m2) administered every 3 weeks (AD), while 49 patients underwent 4 cycles of NC consisted of intravenous injection of doxorubicin (50 mg/m2) and vinorelbine (25 mg/m2) administered every 3 weeks (AN). Response rate and treatment-related toxicities were analyzed by administered chemotherapeutics. Response to NC was also analyzed according to clinicobiological characteristics of the primary tumors.ResultsClinical response was observed in 66% with AN and 81.6% with AD chemotherapy. A complete pathologic response (pCR) was confirmed in 6 patients (11.3%) with AN and in 7 patients (14.3%) with AD after the surgery. Response rate was significantly higher in AD compared with AN (p=0.038), but there was no significant difference between the two group regard to pCR rate. Breast conserving surgery (BCS) was performed in 35.8% of AN group, whereas 20 patients (40.8%) of AD group underwent BCS. The patients with HER2-amplified tumor showed significantly increased response to both types of NC. Pathologic complete response was confirmed in 9 (39.1%) out of 23 HER2-amplified tumors, whereas only 4 (5.1%) of 79 HER2-nonamplified tumors showed pathologic complete response. Febrile neutropenia occurred in 22.6% of total 212 cycles in AN and 38.8% of total 196 cycles in AD. Grade 3/4 neutropenia was observed in 39.6% in AN and 43.9% in AD. Grade 3 mucositis was observed in 26.4% with AN and in 40.8% with AD.ConclusionThere was no significant increase of pCR by AD compared with AN. Long-term follow-up results of our study indicate that clinical outcome after NC was significantly associated with initial response to NC regardless of therapeutic regimens.

Greater Anti-Angiogenic Effects with Docetaxel Compared with Anthracyclines in the Neoadjuvant Treatment of Breast Cancer.

Abstract Background: Dynamic contrast-enhanced MRI (DCE-MRI) allows for the functional assessment of tumour permeability and perfusion and has been previously shown to predict for clinical and pathologic response in women with breast cancer undergoing neoadjuvant anthracycline based chemotherapy1. Changes in DCE-MRI kinetic parameters after 2 cycles of neoadjuvant chemotherapy (NAC) predicts clinical and pathological benefit, with transfer constant Ktrans being the best predictive biomarker. This study examines (1) whether DCE-MRI can predict for final clinical response in women undergoing neoadjuvant docetaxel and (2) whether taxanes demonstrate greater anti-angiogenic activity over anthracyclines in the NAC setting.Methods: 30 patients with histologically proven primary breast cancer (T2-4, N0-1, M0) due to receive neoadjuvant docetaxel chemotherapy underwent DCE-MRI before and after 2 cycles of NAC as part of a prospective study. Whole tumour regions of interest were outlined and values for inflow transfer constant (Ktrans), outflow rate constant (kep), leakage space (ve), initial area under gadolinium-time curve (IAUGC60), relative blood volume (rBV), Mean Transit Time (MTT) and relative blood flow (rBF) calculated. Both baseline and changes in DCE-MRI kinetic parameters were correlated with final clinical response using the Mann-Whitney U test. DCE-MRI results of the docetaxel NAC cohort were compared with a previously analysed cohort of 28 patients who received neoadjuvant FEC chemotherapy1. MRI data acquisition and pharmacokinetic modelling analysis for both cohorts were identical.Results: 25 docetaxel patients were assessable (median age 42, range 26-62; docetaxel 100mg/m2; median number of cycles 4, range 2-6). 1 patient received 1 cycle of docetaxel only and 4 were not able to complete their imaging. There were 21 clinical responders (CR)(9 complete and 12 partial responders) and 4 non-responders (NR)(3 with SD, 1 with PD). There was no significant difference in pretreatment parameters between CR and NR. The median reduction in Ktrans in CR was -58.1% vs -8.9% in NR (95% CI -81.1 to -19.8, p=0.011) and in IAUGC60, -57.6% vs -3.7% (95% CI -79.9 to -14.7, p=0.011). ROC analysis revealed that both Ktrans and IAUGC60 changes were good predictors of clinical response (Ktrans: sensitivity 81%, specificity 100%, area under ROC curve 0.89; IAUGC60: sensitivity 76%, specificity 100%, area under ROC curve 0.89). Comparison of docetaxel versus FEC cohorts showed greater reductions in kinetic parameters in clinical responders in the docetaxel group (Ktrans: -58.1% vs -29.5%, p=0.022; IAUGC60 values: -57.5% vs -20.4%, p=0.006).Discussion: Early changes in DCE-MRI biomarkers depicting tumour vascularity can predict clinical benefit from docetaxel NAC in breast cancer, similar to a finding previously shown for anthracyclines. Significantly larger changes in DCE-MRI biomarkers related to tumour perfusion and permeability in responding patients suggest a greater anti-angiogenic effect with docetaxel.

Pathological lymph node involvement at surgery is a significant predictive factor of recurrence in locally advanced breast cancer treated with concomitant epirubicin–docetaxel neoadjuvant chemotherapy: a cohort study

Neoadjuvant chemotherapy (NAC) is the standard therapy for locally advanced breast cancer. Recently, several studies have revealed that clearance of axillary lymph node involvement is an independent factor for survival irrespective of the response of the primary lesion. However, in daily practice, it is difficult to fully examine every lymph node that has been surgically sampled, in view of pathology laboratory workload and cost. Therefore, in the present study, we adopted the more clinically relevant categorization of evaluating postoperative axillary lymph node status and retrospectively studied its significance in predicting patients' survival. The study cohort consisted of 35 locally advanced breast cancer patients who are treated with concomitant epirubicin-docetaxel. The clinicopathological factors used for analysis were as follows: ERalpha, PgR, p53, HER2, pathological response (in the primary tumor), and axillary lymph node status at surgery. With regard to axillary lymph node status, we categorized patients into two groups: those with pathological lymph node involvement at surgery (pLNI) and those without. Using multivariate analysis, we evaluated the significance of these factors in predicting disease-free survival after surgery. The median follow-up period was 23.4 months (range 4.3-45.4). Multivariate analysis showed significantly reduced disease-free survival associated with pLNI (P = 0.005). pLNI is an excellent prognostic factor for locally advanced breast cancer patients treated with concomitant epirubicin-docetaxel. Use of our criteria may enable large numbers of oncologists to participate in new studies of high-risk cohorts who are refractory to NAC.

Combination epirubicin plus docetaxel neoadjuvant chemotherapy is highly active against breast cancer,

Combination epirubicin plus docetaxel neoadjuvant chemotherapy is highly active against breast cancer,

Neoadjuvant Docetaxel before Radical Prostatectomy in Patients with High-Risk Localized Prostate Cancer

To determine the clinical, pathologic, and molecular effects of neoadjuvant docetaxel chemotherapy in high-risk localized prostate cancer. Patients with biopsy Gleason scores of 8 to 10, serum prostate-specific antigen levels >20 ng/mL, and/or clinical stage T3 disease received weekly docetaxel (36 mg/m2) for 6 months, followed by radical prostatectomy, and were monitored with weekly visits, serum prostate-specific antigen measurements, and endorectal magnetic resonance imaging (MRI). Frozen tumor specimens were collected for microarray analysis. The 19 patients enrolled received 82% of the planned chemotherapy. Toxicity was mild to moderate; fatigue and taste disturbance were common. Prostate-specific antigen declines of >50% were seen in 11 of 19 patients (58%; 95% confidence interval, 33-80%) and endorectal MRI showed maximum tumor volume reduction of at least 25% in 13 of 19 patients (68%; 95% confidence interval, 47-85%) and at least 50% in 4 patients (21%; 95% confidence interval, 6-46%). Sixteen patients completed chemotherapy and had radical prostatectomy; none achieved pathologic complete response. Microarray analysis identified coordinate up-regulation of genes involved in androgen metabolism associated with docetaxel therapy. Specifically, RNA expression for genes that decrease cellular levels of bioactive androgens was coordinately increased in response to chemotherapy. Neoadjuvant docetaxel administered for 6 months before radical prostatectomy is feasible, well tolerated, and often results in prostate-specific antigen declines of >50% and decreased tumor volume on endorectal MRI. No pathologic complete responses were observed. Altered androgen metabolism may partially account for the noted declines in prostate-specific antigen and be a mechanism for chemotherapy resistance.