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We conducted a double-randomised phase III trial to evaluate a concomitant taxane-anthracycline regimen in node-positive breast cancer and the efficacy of trastuzumab in the human epidermal growth factor receptor 2 (HER2)–positive subpopulation. A total of 3010 patients with node-positive breast cancer were randomly assigned to receive 6 cycles of 500 mg/m2 of fluorouracil, 100 mg/m2 of epirubicin and 500 mg/m2 of cyclophosphamide (FEC) or 75 mg/m2 of epirubicin and 75 mg/m2 of docetaxel (ED). Patients with HER2-positive tumours were secondary randomly assigned to either trastuzumab or observation. The primary end-point was disease-free survival (DFS) in the two chemotherapy arms. After a 115-month median follow-up, DFS was not significantly better in the ED arm (DFS: 70%, 95% confidence interval [CI]: 67–72) than in the FEC arm (DFS: 68%, 95% CI: 65–70; hazard ratio [HR] = 0.88, 95% CI: 0.77–1.01; p = 0.064). The OS was not different between FEC (OS: 80%, 95% CI: 78–83) and ED (OS: 81%, 95% CI: 79–83); HR = 0.97, 95% CI: 0.81–1.16; p = 0.729). ED appeared more toxic. In the 528 HER2-positive subset, there was trend for a higher DFS, in the intention-to-treat population, in the trastuzumab arm (DFS: 68%, 95% CI: 61–74) than in the observation arm (DFS: 60%, 95% CI: 54–66; HR = 0.77, 95% CI: 0.57–1.03; p = 0.079). In the per-protocol population, DFS was significantly higher in the trastuzumab arm (DFS: 70%, 95% CI: 63–76) than in the observation arm (DFS: 59%, 95% CI: 53–65; HR = 0.69, 95% CI: 0.51–0.94; p = 0.0156). The OS was not different between these 2 arms. This study did not show superiority of the concomitant anthracycline-taxane arm which was more toxic in high-risk node-positive breast cancer patients. Long-term results of the HER2-positive subpopulation are in line with those of the other adjuvant trastuzumab trials but quantitatively less pronounced mostly because of lack of power. • Long-term outcome was not different between the anthracycline and the concomitant taxane and anthracycline regimens. • In the human epidermal growth factor receptor-2 population, long-term results are in line with those of the other adjuvant trials. [ABSTRACT FROM AUTHOR]

Aims and Objectives: To study the effect of induction chemotherapy (CT) in locally advanced head-and-neck squamous cell carcinoma (LAHNSCC) and to compare the two commonly used regimens of CT, including paclitaxel and cisplatin (CDDP) in one arm and CDDP, methotrexate (MTX), and bleomycin in the other arm as induction CT. Materials and Methods: It is a retrospective study, including 100 histopathologically proven cases of LAHNSCC who received treatment at a government medical college and hospital in Central India between November 2015 and June 2016. All the patients were randomly divided into two arms: arm A received paclitaxel + cisplatin (TP) and arm B received cisplatin + MTX + bleomycin as induction CT had adequate hematologic, hepatic, and renal functions, and their response to treatment was evaluated clinically after each cycle up to three cycles before external beam radiotherapy. Results: The present study showed beneficial effects of induction CT in HNSCC as 82% of the patients showed response or T-downstaging. Among the patients responding to induction CT, 34% showed complete and 48% showed partial response at the primary tumor site according to Response Evaluation Criteria in Solid Tumors. The difference in response between the two arms was statistically significant (P = 0.037). Conclusion: The current study shows the beneficial effects of induction CT in LAHNSCC. No statistically significant difference was seen in the response of both regimens of induction CT in terms of overall survival, but significant disease-free survival and progression-free survival were obtained in the TP arm. [ABSTRACT FROM AUTHOR]

Abstract The need for high-throughput quality control of pharmaceuticals after compounding is often required before the treatment of the patients. Ultra-fast analysis using flow injection analysis coupled to UV spectroscopy and least square matching was assessed for the simultaneous quantification and identification of three therapeutic taxanes after dilution in physiological saline (cabazitaxel, docetaxel, and paclitaxel). In-depth preliminary analysis of the zero and first order UV spectra of the taxanes using principal component analysis (PCA) allowed us focusing on relevant spectral range with very low formulation influence. Least square-matching algorithm available on basic HPLC software was applied to these spectra yielding very high match scores (>999) with significant difference ( P < 0.0001). The approach was qualitatively assessed through specificity and sensitivity which were excellent for the three taxanes (100%, n = 378), irrespective of their formulation. In terms of quantification, satisfactory linearity and accuracy were achieved for each of the taxanes according to their therapeutic range (0.05 to 1.02 mg·mL−1). The RSD (%) of the precision was satisfactory (<3%). Finally, the suitability of the approach for the taxanes QC has been demonstrated under routine application. Graphical abstract Unlabelled Image [ABSTRACT FROM AUTHOR]

Abstract This study identified chemotherapeutic agents that up-regulate programmed cell death ligand-1 (PD-L1) and galectin-9 (Gal-9) in breast cancer cells. Immunohistochemical (IHC) staining was used to evaluate changes in PD-L1 and Gal-9 expression in the tumor tissue of triple-negative breast cancer (TNBC) patients who received anthracycline- and taxane-based neoadjuvant chemotherapy. To determine whether PD-L1 and Gal-9 expression changes were attributable directly to chemotherapeutics, MDA-MB-231 cells and HS578T cells were treated with different concentrations of anthracycline and taxane. Expression levels of PD-L1 and Gal-9 were evaluated and the activation status of NFκB in MDA-MB-231 and HS578T cells was determined to identify the PD-L1 and Gal-9 up-regulation mechanism. Three cases of increased PD-L1 expression and two of increased Gal-9 expression were observed among the TNBC patients. PD-L1 and Gal-9 expression were up-regulated by anthracycline and taxane in MDA-MB-231 cells, but not in HS578T cells. Increased nuclear levels of NFκB were observed in MDA-MB-231 cells treated with 0.5 μM epirubicin. Anthracycline and taxane up-regulated PD-L1 and Gal-9 expression in some subtypes of TNBC. This study provides useful reference data for clinical trials investigating combination treatments with immune checkpoint inhibitors and chemotherapy. [ABSTRACT FROM AUTHOR]

Abstract: Aim: This multicenter, observational study aimed to investigate the survival benefit of eribulin as well as that of taxane‐based regimens in Japanese patients with metastatic breast cancer (MBC) in a real‐world setting. Methods: This study enrolled women with MBC who received eribulin or taxane‐based regimens with or without bevacizumab in routine clinical practice from July 2011 to March 2014. Patients were followed until September 2015. The primary endpoint was overall survival (OS). Secondary endpoints included progression‐free survival (PFS), post‐progression survival (PPS) and adverse events. Efficacy findings were adjusted according to demographics. Results: In total, 216 patients receiving eribulin monotherapy (n = 101), taxane monotherapy (n = 73) or taxane plus bevacizumab (n = 42) were followed for a median time of 15.4 months. Median OS, PFS and PPS were 22.3, 8.1 and 14 months in the eribulin monotherapy group; 13.2, 3.6 and 7.6 months in the taxane monotherapy group; and 12.9, 5.7 and 6.3 months, in the taxane plus bevacizumab group, respectively. The incidence of neutropenia was 67.3, 41.1 and 16.7%, and the incidence of grade 4 neutropenia was 1.0, 8.2 and 7.1% in the eribulin monotherapy, taxane monotherapy and taxane plus bevacizumab groups, respectively. One patient (1.0%) discontinued eribulin and 18 patients (15.7%) discontinued taxane‐based regimens because of adverse events. Conclusion: In Japanese MBC patients in a real‐world setting, eribulin showed a survival benefit and tolerability similar to that in previous reports. [ABSTRACT FROM AUTHOR]

Taxanes are chemotherapeutic drugs employed in the clinic to treat a variety of malignancies. Despite their overall efficacy, cancer cells often display resistance to taxanes. Therefore, new strategies to increase the effectiveness of taxane-based chemotherapeutics are urgently needed. Multiple molecular players are linked to taxane resistance; these include efflux pumps, DNA repair mechanisms, and hypoxia-related pathways. In addition, emerging evidence indicates that both non-coding RNAs and epigenetic effectors might also be implicated in taxane resistance. Here we focus on the causes of taxane resistance, with the aim to envisage an integrated model of the ‘taxane resistance phenome’. This model could help the development of novel therapeutic strategies to treat taxane-resistant neoplasms. [ABSTRACT FROM AUTHOR]

Background Treatment option in patients with metastatic castration-resistant prostate cancer (mCRPC) previously treated with docetaxel (DOC), cabazitaxel (CABA) and new hormone therapy (NHT) is limited. Rechallenge with DOC is limited because of cumulative toxicities. This study investigated the activity and safety of CABA rechallenge in mCRPC. Patients and methods Clinical data were collected retrospectively in 17 centres in Europe. Eligible patients had undergone rechallenge with cabazitaxel after three previous lines of treatment (DOC, NHT and CABA, in any order). Overall survival (OS) and progression-free survival (PFS) were estimated by the Kaplan–Meier method. Data on toxicities were collected. Results A total of 69 of 562 patients (Eastern Cooperative Oncology Group performance status 0–1 69%) were rechallenged with CABA (25 mg/m 2 q3w, 58%; 20 mg/m 2 q3w, 27.5%; other, 14.5%) for 1–10 (median 6) cycles; 76.8% received prophylactic granulocyte colony-stimulating factor. Median radiological or clinical PFS with CABA rechallenge was 7.8 months and 11.9 months with initial CABA therapy. OS was 13.7 months (95% confidence interval [CI]: 9.3–15.7) from the first CABA rechallenge cycle, 59.9 months (47.8–67.1) from the first life-extending therapy in mCRPC and 78.3 months (66.4–90.7) from mCRPC diagnosis. Best clinical benefit was improved (34.3%) or stable (47.8%). Lack of response to rechallenge occurred in 17.9% of patients (3.1% with initial CABA). The level of prostate-specific antigen decreased by ≥ 50% in 24% of patients at rechallenge (71% with initial CABA). There was no grade ≥III peripheral neuropathy or nail disorders. Conclusions CABA rechallenge may be a treatment option without cumulative toxicity in heavily pretreated patients with mCRPC who are still fit and had a progression >3 months after the last CABA injections. [ABSTRACT FROM AUTHOR]

Background: The primary side effect of adjuvant chemotherapy with taxanes is the taxane-induced peripheral neuropathy (TIPN), which may have substantial negative impacts on patients' quality of life (QOL). We investigated the effect of pregabalin and duloxetine on QOL of breast cancer patients who experienced TIPN. Materials and Methods: This was a randomized, double-blind clinical trial conducted at a chemotherapy center of Mazandaran University of Medical Sciences, Sari, Iran. Breast cancer patients 18 or more years old were included if they received paclitaxel or docetaxel and experienced neuropathy grade one or higher; and neuropathic pain score of four or more. Patients were treated with pregabalin or duloxetine until 6 weeks. Assessment of sensory neuropathy and QOL was performed at baseline, and 6 weeks after the initiation of the treatment. Results: At baseline, the mean score of global health status/QOL scale for pregabalin and duloxetine groups were 61 (standard deviation [SD]; 5.11) and 60.28 (SD; 5.44), respectively (P = 0.54). After 6 weeks, both interventions were associated with improvement of global QOL compared to baseline. The global health status/QOL score was not different between two groups after 6 weeks. While the emotional functioning was improved more favorably with duloxetine (P < 0.001); pregabalin was associated with more improvement in insomnia and pain scores (P = 0.05 and P < 0.001, respectively). Conclusion: Pregabalin as well as duloxetine improve the global QOL of breast cancer patients with TIPN. Different effects of treatments on subscale of QLQ-C30 could help clinicians to select the appropriate agent individually. [ABSTRACT FROM AUTHOR]

Purpose: The primary aim of this study was to determine cabazitaxel's affinity for the ABCB1/P-glycoprotein (P-gp) transporter compared to first-generation taxanes.Methods: We determined the kinetics of drug accumulation and retention using [14C]-labeled taxanes in multidrug-resistant (MDR) cells. In addition, membrane-enriched fractions isolated from doxorubicin-selected MES-SA/Dx5 cells were used to determine sodium orthovanadate-sensitive ATPase stimulation after exposure to taxanes. Custom [3H]-azido-taxane analogues were synthesized for the photoaffinity labeling of P-gp.Results: The maximum intracellular drug concentration was achieved faster with [14C]-cabazitaxel (5 min) than [14C]-docetaxel (15-30 min). MDR cells accumulated twice as much cabazitaxel than docetaxel, and these levels could be restored to parental levels in the presence of the P-gp inhibitor PSC-833 (valspodar). Efflux in drug-free medium confirmed that MDR cells retained twice as much cabazitaxel than docetaxel. There was a strong association (r2 = 0.91) between the degree of taxane resistance conferred by P-gp expression and the accumulation differences observed with the two taxanes. One cell model expressing low levels of P-gp was not cross-resistant to cabazitaxel while demonstrating modest resistance to docetaxel. Furthermore, there was a 1.9 × reduction in sodium orthovanadate-sensitive ATPase stimulation resulting from treatment with cabazitaxel compared to docetaxel. We calculated a dissociation constant (Kd) value of 1.7 µM for [3H]-azido-docetaxel and ~ 7.5 µM for [3H]-azido-cabazitaxel resulting in a 4.4 × difference in P-gp labeling, and cold docetaxel was a more effective competitor than cabazitaxel.Conclusion: Our studies confirm that cabazitaxel is more active in ABCB1(+) cell models due to its reduced affinity for P-gp compared to docetaxel. [ABSTRACT FROM AUTHOR]

Purpose: The benefit of adding docetaxel, cisplatin and 5-fluorouracil (TPF) induction chemotherapy to chemoradiotherapy (CRT) in head and neck squamous cell carcinoma (HNSCC) remains uncertain. We aimed to investigate whether ICT is well tolerated when given with prophylactic treatment against predicted adverse effects and which patients benefit most.Methods: A single-centre audit identified 132 HNSCC patients with stage IVa/b neck node-positive disease, prescribed TPF followed by CRT. TPF involved three cycles of docetaxel (75 mg/m2 IV) and cisplatin (75 mg/m2 IV) on day 1 plus 5-FU (750 mg/m2 IV) on days 2–5. Planned CRT was 66 Gy in 30 fractions of intensity-modulated radiotherapy with concurrent cisplatin (100 mg/m2 IV) at the beginning of week 1 and 4 (days 1 and 22). All patients received prophylactic antibiotics and granulocyte colony-stimulating factor.Results: Median follow-up was 39.5 months. 92.4% of patients completed three cycles of TPF; 95.5% of patients started chemoradiotherapy. Grade 3/4 adverse events were low (febrile neutropenia 3.0%), with no toxicity-related deaths. 3-year overall survival was 67.2%; disease-specific survival was 78.7%; locoregional control was 78.3%. Distant metastases rate was 9.8% (3.0% in those without locoregional recurrence). Good performance status (p = 0.002) and poor tumour differentiation (p = 0.018) were associated with improved overall survival on multivariate analysis.Conclusion: With prophylactic antibiotics and granulocyte colony-stimulating factor TPF was well tolerated with good survival outcomes. TPF should remain a treatment option for stage IV neck node-positive patients with a good performance status. The use of tumour grade to aid patient selection for TPF warrants investigation. [ABSTRACT FROM AUTHOR]

Purpose: Multidrug resistance mediated by ABCB1 has been perceived to be one of the obstacles for cancer chemotherapy. This meta-analysis was performed to verify the effect of the ABCB1 rs1045642 and rs1128503 polymorphisms on the response to Taxane-containing chemotherapy.Methods: Pooled odds ratios (ORs) and corresponding 95% confidence intervals (CIs) were employed to evaluate the impact of these two ABCB1 polymorphisms. R scripts were developed to perform the meta-analysis.Results: A total of nine articles (including nine studies for rs1045642 and five for rs1128503) were collected in our systematic review. However, our meta-analysis showed no significant effect of these two ABCB1 polymorphisms on the response to Taxane-containing regimens.Conclusions: This study highlights the unsuitability of relying on the ABCB1 rs1045642 and rs1128503 polymorphisms as therapeutic response biomarkers of Taxane-containing chemotherapy. Further polycentric studies in larger and multiracial populations are needed to validate the conclusions. [ABSTRACT FROM AUTHOR]

Paclitaxel (PTX) and docetaxel (DTX) are highly effective chemotherapeutic agents against breast cancer cells. Existing PTX and DTX formulations, however, contain excipients that result in a multitude of side-effects. The objective of the present study was to develop novel self-microemulsifying formulations of PTX and DTX with significantly lower excipient content by utilizing the high solubility of taxanes in sulforaphane (SFN). SFN-enabled microemulsions were developed by a screening process in which optical microscopy and absorbance data were used to monitor the physical stability of the dispersions. Optimized formulations contained vitamin E TPGS and transcutol to aid in taxane dissolution in water and the formation of transparent microemulsions (< 20 nm). SFN microemulsions were stable in different dilution media and storage temperatures and had no hemolytic effect on RBCs. When tested in vitro against MDA-MB-231 and MCF7 cancer cells by IncuCyte ® live cell analysis and CellTiter-Blue ® assay, taxanes/SFN microemulsions showed similar activity as the commercial taxanes injection solutions. SFN was only found to potentiate the activity of taxanes when used at high concentrations. This study highlighted the unique properties of SFN and its potential use in reformulating taxanes with high drug load and significantly lower excipient content than the commercial products. [ABSTRACT FROM AUTHOR]

The clinicopathological significance and prognostic value of the expression of proteins associated with autophagy, beclin 1 (BECN1), 1A/1B-light chain 3 (LC3) and high mobility group box-1 protein (HMGB-1), were investigated in patients with ovarian carcinoma, receiving combination chemotherapy with a platinum agent and a taxane. Immunohistochemical staining was performed for autophagy-associated proteins in tumor tissues from 141 patients with ovarian carcinoma. Clinical data were collected retrospectively by reviewing medical charts, and the association between protein expression, clinicopathological features and survival was investigated. Amongst 141 ovarian carcinoma samples, the loss of BECN1, LC3, and HMGB-1 expression was identified in 59 (41.8%), 35 (24.8%), and 66 (46.8%) samples, respectively. Clinicopathological factors were not significantly associated with the loss of BECN1 expression. However, significant associations were demonstrated between the expression of BECN1, LC3, and HMGB-1. In addition, loss of BECN1 expression demonstrated a significant association with poor progression-free and poor overall survival. Multivariate analysis demonstrated that loss of BECN1 expression and postoperative residual tumor were significant independent predictors of poor progression-free survival and poor overall survival. These results indicated that loss of BECN1 expression in ovarian carcinoma is a negative prognosticator in patients receiving platinum-based chemotherapy. Assessment of BECN1 expression may be useful for predicting an unfavorable response to platinum-based chemotherapy in ovarian carcinoma. [ABSTRACT FROM AUTHOR]

Objective To examine survival after recurrence (SAR) among women with recurrent uterine carcinosarcoma who received a taxane/platinum doublet as the first-line salvage chemotherapy. Methods We retrospectively examined 148 women with recurrent uterine carcinosarcoma who received salvage chemotherapy within a cohort of 906 uterine carcinosarcomas. An independent association of salvage chemotherapy type and SAR was examined with multivariate analysis. Results There were 71 (48.0%) women who received a taxane/platinum regimen. On univariate analysis, women who received a taxane/platinum doublet had a higher 2-year SAR rate compared to women who received non-taxane/platinum regimens (55.5% versus 34.8%, P < 0.001). On multivariate analysis, use of taxane/platinum regimen was independently associated with improved SAR compared to the non-taxane/platinum regimens (adjusted-hazard ratio [HR] 0.56, 95% confidence interval [CI] 0.35 to 0.91, P = 0.02). When stratified by disease-free interval, women with a disease-free interval ≥ 6 months who received a taxane/platinum doublet had a higher 2-year SAR rate compared to those who received non-taxane/platinum regimens (61.9% versus 40.0%, HR 0.46, 95% CI 0.28 to 0.75, P = 0.002); conversely, in women with a disease-free interval < 6 months, 2-year SAR rates were similar between the two groups (20.5% versus 18.4%, HR 0.80, 95% CI 0.33 to 1.90, P = 0.61). Among women who received a taxane/platinum doublet as adjuvant chemotherapy, re-treatment with taxane/platinum doublet as salvage chemotherapy remained beneficial (2-year SAR rate, 62.1% versus 39.7%, HR 0.40, 95% CI 0.18 to 0.86, P = 0.019). Conclusion Our study suggests that taxane/platinum doublet may be a more effective chemotherapy regimen compared to other regimens among women with recurrent uterine carcinosarcoma, especially for those who had a disease-free interval of ≥ 6 months. [ABSTRACT FROM AUTHOR]

S-1 and irinotecan combination is attractive for breast cancer refractory to anthracyclines and taxanes. Patients with advanced human epidermal growth factor receptor 2 ( HER2)-negative breast cancer previously treated with anthracyclines and taxanes were eligible. Patients with brain metastases and homozygous for UGT1A1 *6 or *28 or compound heterozygous (* 6/ *28) were excluded. A dose-escalation design was chosen for the phase I portion (level 1: irinotecan 80 mg/m2 days 1-8 and S-1 80 mg/m2 days 1-14 every 3 weeks; level 2: irinotecan 100 mg/m2 and S-1 80 mg/m2). Study objectives included determination of the recommended dose for phase II, response rate, progression-free survival ( PFS), and safety. Pharmacokinetics and CD34+ circulating endothelial cells ( CECs) as pharmacodynamics were also analyzed. Thirty-seven patients were included. One patient at each level developed dose-limiting toxicities; therefore, level 2 was the recommended dose for phase II. Diarrhea was more common in patients possessing a *6 or *28 allele compared with wild-type homozygous patients (46% and 25%). Among 29 patients treated at level 2, PFS was longer for UGT1A1 wt/*6 and wt/*28 patients than for wt/ wt patients (12 vs. 8 months, P = 0.06). PFS was significantly longer in patients with a larger-than-median SN-38 area under the curve ( AUC) than in those with a smaller AUC ( P = 0.039). There was an association between clinical benefit and reduction in baseline CD34+ CECs by S-1 ( P = 0.047). The combination of irinotecan and S-1 is effective and warrants further investigation. [ABSTRACT FROM AUTHOR]

Background: This study evaluated the cost-effectiveness of replacing standard intravenous therapy (taxane) with oral S-1 therapy for first-line metastatic breast cancer treatment.Methods: This cost-effectiveness analysis was based on data from a randomized phase III trial (SELECT BC). As cost-effectiveness was a secondary endpoint of the SELECT BC trial, some of the randomized patients participated in an EQ-5D survey (N = 391) and health economic survey (N = 146). The EQ-5D responses, claims, and prescription data were collected for as long as possible until death. The expected quality-adjusted life years (QALY) obtained from each treatment were calculated using patient-level EQ-5D data, and the expected cost was calculated using patient-level claim data. The analysis was performed from the perspective of public healthcare payers.Results: The estimated EQ-5D least-square means and 95% CI up to 48 months were 0.764 (95% CI, 0.741-0.782) and 0.742 (95% CI, 0.720-0.764) in the S-1 and taxane arms, respectively. The expected QALY was 2.11 for the S-1 arm and 2.04 for the taxane arm, with expected costs of JPY 5.13 million (USD 46,600) and JPY 5.56 million (USD 50,500), respectively. These results show that S-1 is cost-saving. According to probabilistic sensitivity analysis, S-1 was dominant with a probability of 63%. When the willingness to pay (WTP) value was JPY 5 million (USD 45,500) per QALY, the probability of being cost-effective was 92%.Conclusions: Our results show that the introduction of oral S-1 therapy for metastatic breast cancer is highly likely to be cost-effective.Trial Registration: UMIN CTR C000000416 . Registered on May 10, 2006. [ABSTRACT FROM AUTHOR]

Objectives: The efficacy of various chemotherapy regimens in nasopharyngeal carcinoma (NPC) remains under debate. We compared the efficacy and toxicity of a taxane-based regimen and regimen including fluorouracil in NPC.Materials and Methods: Eight-hundred and six patients with stage II-IVB NPC from four institutions in China were pair-matched (1:1 ratio) to the cisplatin plus fluorouracil (PF) group or cisplatin plus taxanes (TP) group using eight clinical factors. Overall survival (OS), disease-free survival (DFS), locoregional relapse-free survival (LRRFS) and distant metastasis-free survival (DMFS) were assessed using the Kaplan-Meier method and Cox regression model. Toxicities were assessed in all patients.Results: Three-year DFS was significantly better in the TP group than PF group (82.5% vs. 72.7%, P=0.002), with no significant difference in OS, LRRFS or DMFS. TP led to significantly better DFS compared to PF in the subgroups advanced stage NPC, patients aged ≤45-years-old and female patients. In multivariate analysis, chemotherapy regimen was an independent prognostic factor for DFS [hazard ratio, 0.591, 95% CI 0.444-0.786, P=0.000]. Grade 3-4 leukopenia, neutropenia and anemia were significantly more common in the TP group; grade 3-4 mucositis, vomiting, vasculitis and diarrhea were more common in the PF group.Conclusion: Taxane-based regimens have a higher efficacy in NPC than regimens including fluorouracil, especially in patients with advanced stage, patients aged≤45-years-old and female patients. [ABSTRACT FROM AUTHOR]

Purpose The purpose of this study was to evaluate the impact of postmastectomy radiotherapy (PMRT) on loco-regional recurrence-free survival (LRRFS), disease-free survival (DFS), and overall survival (OS) in pT1-2N1 patients treated with taxane-based chemotherapy. Materials and Methods We retrospectively reviewed the medical data of pathological N1 patients who were treated with modified radical mastectomy and adjuvant taxane-based chemotherapy in 12 hospitals between January 2006 and December 2010. Results We identified 714 consecutive patients. The median follow-up duration was 69 months (range, 1 to 114 months) and the 5-year LRRFS, DFS, and OS rates were 97%, 94%, and 98%, respectively, in patients who received PMRT (PMRT [+]). The corresponding figures were 96%, 90%, and 96%, respectively, in patients who did not receive PMRT (PMRT [-]). PMRT had no significant impact on survival. Upon multivariable analysis, only the histological grade (HG) was statistically significant as a prognostic factor for LRRFS and DFS. In a subgroup analysis of HG 3 patients, PMRT (+) showed better DFS (p=0.081). Conclusion PMRT had no significant impact on LRRFS, DFS, or OS in pT1-2N1 patients treated with taxane- based chemotherapy. PMRT showed a marginal benefit for DFS in HG 3 patients. Randomized studies are needed to confirm the benefit of PMRT in high risk patients, such as those with HG 3. [ABSTRACT FROM AUTHOR]

Purpose: Taxane monotherapy is widely used for advanced gastric cancer (AGC) after failure of standard first-line chemotherapy with fluoropyrimidine and cisplatin. Triplet chemotherapy with docetaxel, cisplatin, and S-1 (DCS) is a promising regimen for first-line chemotherapy of AGC. The aim of this study was to evaluate the efficacy of taxane monotherapy in patients refractory to DCS.Methods: We retrospectively evaluated the efficacy and safety of taxane monotherapy in patients with AGC refractory to first-line therapy with DCS between January 2010 and April 2015. Selection criteria were as follows: ECOG PS of 0-2, treatment with taxane monotherapy in second-line or third-line therapy after failure of second-line irinotecan, absence of massive ascites, and adequate organ function.Results: A total of 30 patients were included in this study. Of these, 15 patients received paclitaxel while another 15 received nanoparticle albumin-bound paclitaxel in either second- or third-line treatment. Median age for the second/third-line group was 64.0/62.0 (range 27-75/42-75); 14/13 (93.3/86.7%) had ECOG PS of 0 or 1. No patients achieved complete or partial response and stable disease was observed in 37.5/35.7% of the patients in the second/third line. Median progression-free survival and overall survival were 3.4 and 5.8 months in the second-line group, and 2.0 and 4.5 months in the third-line group, respectively. The incidences of any grade ≥3 adverse events in the second-line group and the third-line group were 60.0 and 33.3%, respectively. There was no treatment-related death.Conclusions: Taxane monotherapy after DCS failure had acceptable toxicities but was ineffective in AGC patients. [ABSTRACT FROM AUTHOR]

Class III β-tubulin (TUBB3) and Topoisomerase-II (topo-II) are considered to be the predictors of therapeutic efficacy and outcome in several types of human neoplasm. However, whether TUBB3 or topo-II may predict the response to combination chemotherapy and prognosis in patients with advanced thymic carcinoma (ATC) remains unclear. The aim of the present study was to investigate the prognostic significance of TUBB3 and topo-II expression levels in ATC. A total of 34 patients with ATC who received combination chemotherapy were enrolled in the present study. Immunohistochemical analysis was used to examine the expression of TUBB3, topo-II and Ki-67 in tumor specimens obtained by surgical resection or biopsy. TUBB3 and topo-II were highly expressed in 38 and 53% of the tumors, respectively. Progression-free survival (PFS) was significantly shorter in patients with high levels of TUBB3 compared with those with low levels of TUBB3 (P<0.01), whereas no significant difference in PFS between patients with high and low topo-II expression levels was observed (P=0.31). Patients with overexpression of TUBB3 or topo-II exhibited significantly shorter overall survival rates (OS) compared with those patients with low levels of expression of these proteins (TUBB3; P=0.01, topo-II; P=0.01). Multivariate analysis demonstrated that a high level of TUBB3 expression was an independent unfavorable prognostic factor for OS, and a high level of topo-II expression tended to correlate with poor prognosis without statistical significance. Additionally, a subset analysis demonstrated that the treatment with taxanes, but not topo-II inhibitors, tended to prolong OS in patients with TUBB3 overexpression and there was significant survival advantage of chemoradiotherapy over chemotherapy in patients with topo-II overexpression. It was revealed that an enhanced expression of TUBB3 or topo-II was clearly associated with clinical outcomes in patients with ATC who received combination chemotherapy, including taxanes or topo-II inhibitors, suggesting the prognostic significance of these markers. [ABSTRACT FROM AUTHOR]

Background: Because standard chemotherapy for advanced gastric cancer consists of oral fluoropyrimidines plus platinum as first-line therapy, with paclitaxel plus ramucirumab as the second line, irinotecan is usually positioned as third-line chemotherapy in clinical practice in Japan. Methods: A retrospective evaluation was conducted to determine the efficacy and safety of irinotecan as third-line chemotherapy for advanced gastric cancer in patients refractory or intolerant to fluoropyrimidines, platinum, and taxanes. Results: Between February 2008 and December 2013, 52 patients received third-line irinotecan monotherapy. Among the 32 patients with measurable lesions, 1 patient achieved a confirmed partial response and 6 patients had stable disease. The overall response rate was 3% and the disease control rate was 22%. Median progression-free survival was 2.3 months [95% confidence interval (CI), 1.8-2.8] and median overall survival was 4.0 months (95% CI, 2.6-5.3). The most common adverse events of grade 3 severity or higher were neutropenia (27%), febrile neutropenia (12%), anorexia (12%), and diarrhea (6%). Although no treatment-related deaths occurred, 2 patients (4%) died of disease progression within 30 days after the last administration of irinotecan. Conclusion: Irinotecan monotherapy appears to be tolerated but was shown to have modest activity as third-line chemotherapy for advanced gastric cancer. [ABSTRACT FROM AUTHOR]

Objective: Several pathways are known to be activated during metastasis and treatment of cancer. We investigated the role of osteopontin (OPN) and stathmin-1 (STHMN1) in metastatic castrate-resistant (mCRPC). Methods: We included 30 patients who received at least 6 cycles of taxane regimen for metastatic mPC in the present study. For this study retrospective data was taken from Firat University, Faculty of Medicine, Medical Oncology Department between 2009 and 2015. OPN expression and STHMN1 expression were retrospectively evaluated by immunohistochemical staining in biopsy specimens. The relationship between the expression levels of OPN and STMN1 and the response to taxane based regimen and survival was analyzed. Results: There was mild or strong overexpression of OPN and STHMN1 in all the patients. STHMN1 expression was mildly positive (+2) in four of the cases (13.2%) while it was strongly positive (+3) in 25 (83.4%) cases. Similarly, OPN expression was mildly positive (+2) and strongly positive (+3) in five (16.6%) and 25 (87.4%) patients, respectively. There was no significant correlation between the expression levels of STHMN1 and OPN, survival and response to taxane based regimen (p>0.05); however, OPN overexpression showed a significant correlation with lower Gleason scores (GS) (p:0.032). Conclusions: STHMN1 and OPN may be prognostic markers although they are not predictive markers of response to treatment in mCRPC. The overexpression of OPN may help identifying patients with lower GS. [ABSTRACT FROM AUTHOR]

Anthracyclines are used in breast cancer both in early and advanced stages and their recommendation together with taxanes, either concurrently or sequentially, is debatable and individualized by phenotype. Circulating biomarkers have already been introduced in clinical practice for metastatic disease monitoring. We questioned whether it might be a role for these markers in neoadjuvant and adjuvant settings too and a general review was conducted. CK18 and CTC were found predictive for anthracycline related response in preoperative setting. Soluble E-cadherin is promising, a retrospective analysis showing a direct correlation with clinical response. CEA, CA 15-3 and HER2 ECD are not of interest for their predictive role. [ABSTRACT FROM AUTHOR]

Background: Taxanes are drugs used in various chemotherapeutical protocols to treat solid tumors. They have multiple systemic adverse effects, such as bone marrow suppression, alopecia, nausea, and vomiting, and may rarely cause ocular symptoms. In the past decade, a few reported cases have shown the occurrence of a cystoid macular edema with significant visual loss after the use of a taxane-based chemotherapy. The aim of this study was to compare the central macular thickness (CMT) before and after the initiation of a taxane-based therapy in visually asymptomatic patients and to elucidate the possible impact of these drugs on the vision of cancer patients. Methods: Patients with a confirmed diagnosis of a solid tumor were screened for any ophthalmic disease before inclusion and had a baseline macular spectral domain optical coherence tomography (OCT; RTVue-100; Optovue Inc., Fremont, CA, USA) before the initiation of a taxane-based chemotherapy according to different protocols, such as 4EC-4T, 3FEC/3T, or 4TC. OCT was repeated after 4 cycles (or 3 months) of treatment, and CMT was compared to baseline. Patients presenting diabetic retinopathy, age-related macular degeneration or any condition that causes macular edema confirmed by ophthalmic examination were excluded. Results: Fifty eyes of 25 patients were included; 92% of the subjects were female with a mean age of 48.52 years, 88% were diagnosed with breast cancer, 8% with esophageal cancer, and 4% with ovarian cancer. Docetaxel was the taxane administered to 92% of the patients. The received dose of docetaxel ranged between 110 and 160 mg. The other patients had paclitaxel in their protocols. No significant macular edema or drop in visual acuity were noted in any patient. Nevertheless, the mean CMT was found to be increased, particularly in the parafoveal and perifoveal areas (mean difference of +2.22 µm; p = 0.001). Conclusion: Taxane-based chemotherapy regimens seem to increase macular thickness, with a relative sparing of the fovea, in patients without significant macular edema. Further research is required to better explain the pathophysiology and possible impact of this phenomenon. [ABSTRACT FROM AUTHOR]

Background. Adjuvant chemotherapy for high-risk early-stage breast cancer patients significantly improves longterm treatment results. The decision to administer chemotherapy is made based primarily on prognostic factors (defined by the pathological characteristics of the primary tumour and regional lymph nodes) and also on patientrelated factors, such as age, menopausal status and comorbidities. The guidelines on adjuvant chemotherapy have been established and reviewed for many years by several medical societies (NCCN, ESMO, PTOK, PUO) and experts of St. Gallen International Breast Cancer Conference. The aim of this study was to assess the pattern of adjuvant chemotherapy administration that had been routinely prescribed in four cancer centres in various regions of Poland (Opole, Kraków, Białystok, Poznań). Methods. 218 early-stage breast cancer patients treated in selected cancer centres during 3 consecutive months of 2014 have been included in the analysis. The medical charts of the patients have been carefully evaluated. Data on the adjuvant chemotherapy administration have been reviewed retrospectively. Results. The percentage of IHC tests in the analysed group was satisfactory. As much as 8 different chemotherapy regimens have been recorded. 98% of patients received anthracycline-based chemotherapy. Almost half of the patients (48.6%; 106/218) received taxanes. However, up to 27% (30/111) of patients with involved lymph nodes (pN+) did not received taxanes in the adjuvant setting. Trastuzumab was most frequently administered sequentially, which may be considered suboptimal. [ABSTRACT FROM AUTHOR]

Purpose: The goal of chemotherapy for metastatic breast cancer (MBC) is to prolong survival and maintain health-related quality of life. This study aimed to evaluate long-term health status of patients with MBC who participated in the phase III randomized SELECT BC trial.Methods: In the SELECT BC trial, patients were randomly allocated to the S-1 or taxane (paclitaxel or docetaxel) arm. Health status was assessed by EQ-5D at pre-treatment, 3 and 6 months after randomization, and every 6 months thereafter to the extent possible. Least square mean scores were assessed to compare EQ-5D index values between groups. Time to deterioration analysis was also performed by defining the minimally important difference of EQ-5D as 0.05 or 0.1.Results: The number of patients for EQ-5D analysis was 175 and 208 in the taxane and S-1 arms, respectively. Least square mean EQ-5D index values up to 60 months were 0.741 (95 % CI [0.713-0.769]) in the taxane arm and 0.748 [0.722-0.775] in the S-1 arm. The EQ-5D index value during PFS up to 12 months in the S-1 was superior to the corresponding index value in the taxane (0.812 [0.789-0.834] vs. 0.772 [0.751-0.792], P = 0.009). Time to deterioration analysis also revealed that S-1 significantly delayed the deterioration of EQ-5D index value during the period before progression (P = 0.002 and 0.003).Conclusions: Our findings suggest that the EQ-5D index value was higher in patients treated with S-1 during first-line chemotherapy. Considering non-inferiority of S-1 in terms of OS, obtained quality-adjusted life years may be greater in the S-1 arm. [ABSTRACT FROM AUTHOR]

Objective: Rhenium-188-HEDP is an effective radiopharmaceutical for the treatment of painful bone metastases from prostate cancer. The effectiveness of the β-radiation emitted by 188Re might be enhanced by combination with chemotherapy, using the radiosensitization concept. Therefore, the authors investigated the combined treatment of the taxanes, docetaxel and cabazitaxel, with 188Re in prostate carcinoma cell lines.Materials and Methods: The cytotoxic effects of single and combined treatment with taxanes and 188Re were investigated in three human prostate carcinoma cell lines (PC-3, DU 145, and LNCaP), using the colony-forming assay. The half maximal effective concentration (EC50) of all individual agents was determined. The combined treatment was studied at 0.25, 0.5, 1, 2, and 4 times the EC50 of each agent. The interaction was investigated with a regression model.Results: The survival curves showed dose-dependent cell growth inhibition for both the taxanes and 188Re. The regression model showed a good capability of explaining the data. It proved additivity in all combination experiments and confirmed a general trend to a slight subadditive effect.Conclusions: This proof-of-mechanism study exploring radiosensitization by combining 188Re and taxanes showed no synergism, but significant additivity. This encourages the design of in vivo studies. Future research should explore the potential added value of concomitant treatment of bone metastases with chemotherapy and 188Re-HEDP. [ABSTRACT FROM AUTHOR]

In this study, callus cultures from leaves and young shoots of Taxus baccata L.were established in Gamborg's B5 medium supplemented with 2,4-dichlorophenoxiacetic acid (2 mg/L), kinetin (0.5 mg/L) and gibberellic acid (0.25 mg/L). Callus growth and taxane production were evaluated using two culture media: Woody Plant Medium and Gamborg's B5 supplemented with picloram (2 mg/L), kinetin (0.1 mg/L) and gibberellic acid (0.5 mg/L). The effect of the inoculum size (50, 100 and 150 g FW/L) and culture media (Woody Plant Medium and Gamborg's B5) with and without the presence of methyl jasmonate (100 μM) on T. baccata cell suspensions was assessed. Taxane analysis revealed that the calus in Gamborg's B5 produced taxol (50 μg/g DW), baccatin III, 10-deacetyl baccatin III and 10- deacetyl taxol. Woody Plant Medium also induced the production of taxol, although to a lesser extent. The optimum inoculum size was 50 g FW/L. In cell suspension cultures, both media had a significant effect on taxane production when supplemented with methyl jasmonate. In WPM, at day 14, a total concentration of 185.35 μg/L of taxol, 172.98 μg/L of baccatin III, 658.97 μg/L of 10-deacetyl baccatin III and 259.75 μg/L 10-deacetyl taxol were obtained, with total excretion of baccatin III and 10-deacetyl taxol to the culture medium. The best culture conditions for producing taxol were found to be WPM supplemented with MeJ. The taxol level achieved in these conditions was 3.4 higher than in the same medium without elicitation and over 9 times higher than in the cultures grown in B5, elicited or not. [ABSTRACT FROM AUTHOR]

To target taxanes to castration-resistant prostate cancer cells, glycol-chitosan nanobubbles loaded with paclitaxel and docetaxel were constructed. The loaded nanobubbles were then combined with Extracorporeal Shock Waves, acoustic waves widely used in urology and orthopedics, with no side effects. Nanobubbles, with an average diameter of 353.3 ± 15.5 nm, entered two different castration-resistant prostate cancer cells (PC3 and DU145) as demonstrated by flow cytometry and immunofluorescence. The shock waves applied increased the amount of intracellular nanobubbles. Loading nanobubbles with paclitaxel and docetaxel and combining them with shock waves generated the highest cytotoxic effects, resulting in a paclitaxel GI50 reduction of about 55% and in a docetaxel GI50 reduction of about 45% respectively. Combined treatment also affected cell migration. Paclitaxel-loaded nanobubbles and shock waves reduced cell migration by more than 85% with respect to paclitaxel alone; whereas docetaxel-loaded nanobubbles and shock waves reduced cell migration by more than 82% with respect to docetaxel alone. The present data suggest that nanobubbles can act as a stable taxane reservoir in castration-resistant prostate cancer cells and shock waves can further increase drug release from nanobubbles leading to higher cytotoxic and anti-migration effect. [ABSTRACT FROM AUTHOR]

Background: Triple negative breast cancer (TNBC) is a highly heterogeneous and aggressive disease, and although no effective targeted therapies are available to date, about one-third of patients with TNBC achieve pathologic complete response (pCR) from standard-of-care anthracycline/taxane (ACT) chemotherapy. The heterogeneity of these tumors, however, has hindered the discovery of effective biomarkers to identify such patients.Methods and Findings: We performed whole exome sequencing on 29 TNBC cases from the MD Anderson Cancer Center (MDACC) selected because they had either pCR (n = 18) or extensive residual disease (n = 11) after neoadjuvant chemotherapy, with cases from The Cancer Genome Atlas (TCGA; n = 144) and METABRIC (n = 278) cohorts serving as validation cohorts. Our analysis revealed that mutations in the AR- and FOXA1-regulated networks, in which BRCA1 plays a key role, are associated with significantly higher sensitivity to ACT chemotherapy in the MDACC cohort (pCR rate of 94.1% compared to 16.6% in tumors without mutations in AR/FOXA1 pathway, adjusted p = 0.02) and significantly better survival outcome in the TCGA TNBC cohort (log-rank test, p = 0.05). Combined analysis of DNA sequencing, DNA methylation, and RNA sequencing identified tumors of a distinct BRCA-deficient (BRCA-D) TNBC subtype characterized by low levels of wild-type BRCA1/2 expression. Patients with functionally BRCA-D tumors had significantly better survival with standard-of-care chemotherapy than patients whose tumors were not BRCA-D (log-rank test, p = 0.021), and they had significantly higher mutation burden (p < 0.001) and presented clonal neoantigens that were associated with increased immune cell activity. A transcriptional signature of BRCA-D TNBC tumors was independently validated to be significantly associated with improved survival in the METABRIC dataset (log-rank test, p = 0.009). As a retrospective study, limitations include the small size and potential selection bias in the discovery cohort.Conclusions: The comprehensive molecular analysis presented in this study directly links BRCA deficiency with increased clonal mutation burden and significantly enhanced chemosensitivity in TNBC and suggests that functional RNA-based BRCA deficiency needs to be further examined in TNBC. [ABSTRACT FROM AUTHOR]

To report the results of the DECT trial, a phase II study of locally advanced or operable HER2-positive breast cancer (BC) treated with taxanes and concurrent anthracyclines and trastuzumab. Eligible patients (stage IIA-IIIB HER2-positive BC, 18-75 years, normal organ functions, ECOG ≤1, and left ventricular ejection fraction (LVEF) ≥55%) received four cycles of neoadjuvant docetaxel, 100 mg/m2 intravenously, plus trastuzumab 6 mg/kg (loading dose 8 mg/kg) every 3 weeks, followed by four 3-weekly cycles of epirubicin 120 mg/m2 and cyclophosphamide, 600 mg/m2, plus trastuzumab. Primary objective was pathologic complete response (pCR) rate, defined as ypT0/is ypN0 at definitive surgery. We enrolled 45 consecutive patients. All but six patients (13.3%) completed chemotherapy and all underwent surgery. pCR was observed in 28 patients (62.2%) overall and in 6 (66.7%) from the inflammatory subgroup. The classification and regression tree analysis showed a 100% pCR rate in patients with BMI ≥25 and with hormone negative disease. The median follow up was 46 months (8-78). Four-year recurrence-free survival was 74.7% (95%CI, 58.2-91.2). Seven patients (15.6%) recurred and one died. Treatment was well tolerated, with limiting toxicity being neutropenia. No clinical cardiotoxicity was observed. Six patients (13.4%) showed a transient LVEF decrease (<10%). In one patient we observed a ≥10% asymptomatic LVEF decrease persisting after surgery. Notwithstanding their limited applicability due to the current guidelines, our findings support the efficacy of the regimen of interest in the neoadjuvant setting along with a fairly acceptable toxicity profile, including cardiotoxicity. Results on BMI may invite further assessment in future studies. J. Cell. Physiol. 231: 2541-2547, 2016. © 2016 The Authors. Journal of Cellular Physiology Published by Wiley Periodicals, Inc. [ABSTRACT FROM AUTHOR]

Aim: To perform a systematic review and meta-analysis of randomized controlled trials to compare the efficacy and safety of doublet versus single agent as salvage treatment for pretreated metastatic breast cancer.Methods: A comprehensive literature search was performed to identify relevant randomized controlled trials (RCTs). All clinical studies were independently identified by two authors for inclusion. Demographic data, treatment regimens, objective response rate (ORR), and progression-free survival (PFS) and overall survival (OS) were extracted and analyzed using Comprehensive MetaAnalysis software (Version 2.0).Results: Thirteen RCTs involving 4878 pretreated metastatic breast cancer patients were ultimately identified. The pooled results demonstrated that doublet combination therapy significantly improved ORR (RR 1.13, 95% CI: 1.01-1.27, p < .001) and PFS (hazard ration [HR] 0.83, 95% CI: 0.73-0.96, p = .011), but not OS (HR 0.93, 95% CI: 0.86-1.01, p = .065). Similar results were observed in sub-group analysis according to treatment regimens. Additionally, more incidences of grade 3 or 4 myelosuppression toxicities nausea and fatigue were observed in doublet combination therapy.Conclusions: In comparison with a single agent alone, doublet combination therapy as salvage treatment for pretreated metastatic breast cancer patients significantly improves ORR and PFS, but not OS. Further studies are recommended to identify patients who will most likely benefit from the appropriate doublet combination therapy. [ABSTRACT FROM AUTHOR]

The inhibitory effect of 13 taxanes isolated from the Chinese yew (Taxus chinensisvar.mairei) on the proliferation of human cervical cancer HeLa cells were examined using an MTT assay. Four compounds having a hydrophobic cinnamate side chain showed antiproliferative activity, which may be due to increased cell permeability. [ABSTRACT FROM PUBLISHER]

Background: Sequential administration of anthracycline and taxane is the current standard of care adjuvant regimen for node-positive early breast cancer. Due to long-term toxicity concerns, anthracycline-free regimens have been developed. We compared a sequential dose-dense anthracycline and taxane regimen with the anthracycline-free regimen of docetaxel and cyclophosphamide. Patients and methods: In this randomized, non-inferiority, phase III trial, women with HER2-negative invasive breast cancer and at least one positive axillary lymph node were randomized to receive either epirubicin (75 mg/m²), 5-fluorouracil (500 mg/m²) and cyclophosphamide (500 mg/m²) every 2 weeks for four cycles, followed by four cycles of docetaxel (75 mg/m²) every 2 weeks with prophylactic G-CSF support (FEC→D) or docetaxel (75 mg/m²) and cyclophosphamide (600 mg/m²) every 21 days for six cycles (TC). The primary end point of the study was the 3-year disease-free survival (DFS) rate. Results: Six hundred and fifty women were randomized to either FEC→D (n = 326) or TC (n = 324). After a median follow-up of 46 and 47 months, the 3-year DFS rate was 89.5% and 91.1% for the FEC→D and TC arm, respectively (hazard ratio = 1.147, 95% confidence interval 0.716-1.839, P = 0.568). Grade 3-4 neutropenia was higher in the TC arm (32.4% versus 10.5%, P = 0.0001). The incidence of neutropenic fever was low (<1%). Nausea, vomiting, hand-foot syndrome and fatigue (grade 3-4) were more common with FEC→D. Acute cardiotoxicity was rare (1 event in each group). There were no toxic deaths. Conclusions: This trial did not clearly demonstrate that TC is non-inferior to dose-dense FEC→D. However, 3-year DFS rates were excellent in both arms for women with node-positive, HER2-negative early breast cancer. [ABSTRACT FROM AUTHOR]

Background Chemo-radiotherapy is standard of care in the treatment of unresectable stage III NSCLC. We aimed at assessing whether the addition of concurrent taxane-chemotherapy to thoracic irradiation following chemotherapy was able to improve treatment outcome. Material and methods In PITCAP trial, patients with unresectable stage III NSCLC were randomized to receive 2 cycles of platinum-paclitaxel followed by 60–61.2 Gy thoracic irradiation (control arm) or by same radiotherapy with concomitant weekly paclitaxel (experimental arm). A literature-based meta-analysis including all studies with same design was also performed. Results At the time of the second interim analysis, when 151 patients were randomized, accrual was terminated. With a median follow-up of 6.1 years, median survival was 13.2 vs 15.1 months, with a 3-year survival rate of 19.5 vs 21.2% in the control and experimental arm, respectively (HR: 0.97; 95% CI 0.69–1.36; p = 0.845). Treatment toxicity was manageable in both arms. The meta-analysis of 5 trials (n = 866) confirmed the lack of a meaningful effect on 1-year overall survival of a taxane added concurrently to radiotherapy. Conclusions These results do not support a meaningful survival benefit with the addition of single agent taxane given concurrently to radiotherapy after platinum-based induction in locally advanced NSCLC. [ABSTRACT FROM AUTHOR]

Purpose: The purpose of this study is to identify risk factors for transient lymphedema (TLE) and persistent lymphedema (PLE) following treatment for breast cancer. Materials and Methods: A total of 1,073 patients who underwent curative breast surgery were analyzed. TLE was defined as one episode of arm swelling that had resolved spontaneously by the next followup; arm swelling that persisted over two consecutive examinations was considered PLE. Results: At a median follow-up period of 5.1 years, 370 cases of lymphedema were reported, including 120 TLE (11.2%) and 250 PLE (23.3%). Initial grade 1 swelling was observed in 351 patients, of which 120 were limited to TLE (34%), while the other 231 progressed to PLE (66%). All initial swelling observed in TLE patients was classified as grade 1. In multivariate analysis, chemotherapy with taxane and supraclavicular radiation therapy (SCRT) were associated with development of TLE, whereas SCRT, stage III cancer and chemotherapy with taxane were identified as risk factors for PLE (p < 0.05). The estimated incidence of TLE among initial grade 1 patients was calculated using up to three treatment-related risk factors (number of dissected axillary lymph nodes, SCRT, and taxane chemotherapy). The approximate ratios of TLE and PLE based on the number of risk factors were 7:1 (no factor), 1:1 (one factor), 1:2 (two factors), and 1:3 (three factors). Conclusion: One-third of initial swelling events were transient, whereas the other two-thirds of patients experienced PLE. Estimation of TLE and PLE based on known treatment factors could facilitate prediction of this life-long complication. [ABSTRACT FROM AUTHOR]

Four novel taxane derivatives, N-debenzoyl-N-methyl-N-heptanoyl-taxol ( 1), N-debenzoyl-N-me-thyl-N-octanoyl-taxol ( 2), N-debenzoyl-N-methyl-N-(4-methylhexanoyl)-taxol ( 3), and N-debenzoyl-N-methyl-N-[(4Z)-1-oxo-4-tenenoyl]-taxol ( 4), were isolated from the ethanol extract of the whole plant of Taxus wallichiana.var.mairer. These structures were identified on the basis of extensive spectroscopic analysis, and their antitumor activity was evaluated against MCF-7, A549, and 3- AO cancer cell lines by the MTT method. Compound 3, the most promising one, exhibited encouraging effect with IC50 of 77 n m in MCF-7 cells, which was almost matching that of positive control Taxol. In further mechanism study, the tubulin polymerization assay demonstrated that four compounds caused shifts from the soluble tubulin (depolymerized tubulin) to the particulate tubulin fraction (polymerized) which was similar to Taxol. These results revealed novel natural products with paclitaxel-likemicrotu-bule-stabilizing activity owned their major importance in the clinical treatment of cancer. [ABSTRACT FROM AUTHOR]

Purpose: Although irinotecan monotherapy is often used in third-line treatment after the failure of taxanes in Japanese clinical practice, its survival benefit is still unclear. The aim of this study is to investigate the efficacy and safety of irinotecan monotherapy as third-line treatment.Methods: Clinical data from consecutive patients in whom irinotecan had been initiated as third-line treatment between December 2003 and July 2015 in Shizuoka Cancer Center were retrospectively analyzed. Patients who were refractory or intolerant to fluoropyrimidine with or without platinum in first-line treatment and subsequent therapy with taxanes were included in this study. Irinotecan was administered at 150 mg/m(2) every 2 weeks.Results: The data of 50 patients who met the inclusion criteria were analyzed. The overall response rate was 18.4 % (7/38) among the patients with measurable disease. The median progression-free survival time was 66 days, and the median survival time was 180 days from the initiation of irinotecan therapy. The major grade 3 or 4 adverse events including neutropenia, fatigue, and anorexia were observed in 12 (24 %), 8 (16 %), and 7 (14 %), respectively. No treatment-related deaths occurred. Thirteen patients (26 %) required a dose reduction to 120 mg/m(2) or less from the initiation of irinotecan.Conclusions: This study suggests that irinotecan as third-line treatment has an anti-tumor effect and is feasible with optimal dose modification for advanced gastric cancer. [ABSTRACT FROM AUTHOR]

Background: Taxane acute pain syndrome (TAPS) is characterized by myalgias and arthralgias starting 24-48 h after taxane-based chemotherapy and lasting for 5-7 days. Relatively little is known about its incidence and impact on quality of life.Objectives: A systematic review was conducted evaluating the incidence of TAPS in breast cancer patients receiving taxane-based chemotherapy.Methods: Embase, Cochrane, and Ovid MEDLINE were searched from 1947 to July 2015. Data was sought from randomized controlled trials (RCTs), prospective and retrospective observational studies. Two reviewers independently screened citations and full text articles. Outcomes of interest were the incidence of TAPS and its impact on quality of life.Results: Of 980 citations identified, 51 relevant studies (27,007 patients) were included. Data came from RCTs (12,357 patients), retrospective (6566 patients) and prospective observational studies (6210 patients). Study sample sizes ranged from 14 to 4149 patients (median 152). Given the significance between study heterogeneity, a meta-analysis was not performed. The incidence of TAPS varied between taxanes: paclitaxel (median 13.1 %, range 0.9-86 %), docetaxel (median 10.5 %, range 3.6-70 %), and nab-paclitaxel (26 %, range 14-43 %). In the metastatic setting, median incidence was 30 % (range 5.4-73 %), compared with 11.3 % (range 0.9-86 %) in the adjuvant setting. Three out of eight studies assessing quality of life demonstrated pain interference with daily activities.Conclusions: The incidence of TAPS varies between taxanes, regimens, and disease settings. In order to identify patients at the greatest risk of TAPS, and hence optimize its prevention and management, standardized methods of diagnosing and measuring TAPS are needed. [ABSTRACT FROM AUTHOR]

The article presents a study which compares rates of febrile neutropenia (FN), overall survival (OS), hormone adherence rates (HA) and disease-free survival (DFS) in women under age 50 and women over 50 years old undergoing 5-flurouracil +epirubicin+cyclophosphamide (FEC-T). Topics discussed include choice of endpoints to assess nausea and vomiting, acute pain syndrome with taxanes, and carcinoid heart disease.

Background: Interindividual variability of pharmacogenetics may account for unpredictable neurotoxicities of taxanes. Methods: From March 2011 to June 2015, female patients with operable breast cancer who had received docetaxel-or paclitaxel-containing adjuvant chemotherapy were included in this study. All patients were treated with single-agent paclitaxel intravenously (IV) 175 mg/m² every 3 weeks for four cycles, or IV 80 mg/m² weekly for 12 cycles, and IV 100 mg/m² docetaxel for four cycles as adjuvant treatment. We evaluated the relationship between neurotoxicity of taxanes and single-nucleotide polymorphisms of ABCB1, CYP3A4, ERCC1, ERCC2, FGFR4, TP53, ERBB2, and CYP2C8 genes. Taxane-induced neurotoxicity during the treatment was evaluated according to the National Cancer Institute Common Toxicity Criteria version 4.03 prior to each cycle. Chi-squared tests were used to compare the two groups, and multivariate binary logistic regression models were used for determining possible risk factors of neuropathy. Results: Pharmacogenetic analysis was performed in 219 females. ABCB1 3435 TT genotype had significantly higher risk for grade ≥2 neurotoxicity (odds ratio [OR]: 2.759, 95% confidence interval [CI]: 1.172-6.493, P: 0.017) compared to TC and CC genotype, and also CYP3A4 392 AA and AG genotype had significantly higher risk for grade ≥2 neurotoxicity (OR: 2.259, 95% CI: 1.033-4.941, P: 0.038) compared to GG genotype. For FDGF4 gene with AG and GG genotype, OR was 1.879 (95% CI: 1.001-3.525, P: 0.048) compared to AA genotype with regard to any grade of neuropathy risk. We could not find any other association of other genotypes with neurotoxicity grades. Conclusion: ABCB1 3435 TT genotype and CYP3A4 392 AA/AG genotypes may be used as predictors of neurotoxicity during taxane chemotherapy. [ABSTRACT FROM AUTHOR]

Over 230,000 new cases of breast cancer are expected to be diagnosed in the United States in 2015. Taxane-based chemotherapy is often an effective treatment, but can also cause adverse symptoms in patients due to neurotoxicity. These side effects can impair postural control in patients; however, this instability has scarcely been quantified. The purpose of this pilot study was to gain insight into the natural history of postural instability in breast cancer patients being treated with taxane-based chemotherapy. Thirty-two breast cancer patients (31 female/1 male; 47.6±11.2 year; 16 stage II/16 stage III) completed eyes open and eyes closed quiet standing trials in the oncology clinic where they were being treated. These trials were collected at five timepoints throughout their chemotherapy treatment: (1) before initiating chemotherapy to provide a baseline, (2-4) before starting subsequent chemotherapy cycles, and (5) 1-3 months after receiving their last taxane infusion. After the first chemotherapy cycle, patients demonstrated increases in 95% confidence ellipse area of center of pressure (CoP) [45.2%, p=0.01] and root mean squared CoP excursion [18%, p=0.006] compared to baseline values for the eyes closed condition. These balance deficiencies progressed with cumulative taxane exposure. Postural instability persisted 1-3 months after completing chemotherapy with increases in 95% CoP ellipse area [86.8%, p=0.002], root mean squared CoP excursion [32.6%, p=0.001], and mean CoP velocity [30.4%, p=0.024]. The balance impairments demonstrated by patients in this study appear to be clinically relevant when compared to balance impairments previously reported in other patient populations. [ABSTRACT FROM AUTHOR]

Objective We compared tolerability, toxicity, response, and interval debulking surgery (IDS) outcomes between patients who received weekly dose-dense paclitaxel (DDP) and every three-week platinum to standard every three-week taxane plus platinum neoadjuvant chemotherapy (NACT) for advanced epithelial ovarian cancer (EOC). Methods We conducted a retrospective study of patients receiving NACT at our center between June 1, 2012 and July 31, 2015. Patients with stage III/IV EOC who received at least one cycle of DDP (weekly paclitaxel plus every three-week carboplatin) or standard taxane (every three-week paclitaxel or docetaxel plus carboplatin) therapy were included. Abstracted data included demographics, tolerability, grade 3/4 toxicity, response, and IDS outcomes. Fisher's exact and student t -test were used for statistical significance. Results Twenty-one patients received DDP and 40 received standard taxane. Tolerability was comparable. More patients receiving DDP experienced grade 3 or 4 toxicity when considered in aggregate (86% vs. 40%; p = 0.001). Pathologic complete response (pCR) was achieved in 14% of DDP patients versus 3% of standard (p = 0.11). 48% of patients in the DDP group were debulked to no residual disease (NRD) versus 28% in the standard group (p = 0.16). Conclusions While associated with an increase in severe toxicity compared to standard three-week taxane, DDP appears to facilitate higher rates of pCR and NRD for patients receiving NACT in this preliminary study. These results warrant further investigation of DDP for patients with advanced EOC and assessment of impact on long-term survival outcomes. [ABSTRACT FROM AUTHOR]

Background: Maintenance strategies beyond response or tumor stabilization with first-line chemotherapy in metastatic breast cancer (MBC) have not been extensively studied. Endocrine therapy combined with continued bevacizumab may be a helpful option for estrogen receptor (ER)-positive MBC. Patients and methods: In this prospective, open-label, phase III study, patients with histologically confirmed ERpositive, HER2-negative MBC and non-progressive disease after 16-24 weeks of taxane plus bevacizumab (T + BEV) were randomized to continuation of T + BEV or maintenance bevacizumab plus exemestane (E + BEV). The primary end point was progression-free survival (PFS) from randomization. To have 80% power to detect an improvement in the 6-month PFS rate (PFS6m) from 50% to 65%, 186 assessable patients were needed for a total of 141 PFS events. An interim analysis was planned after 40% of the required events. Results: The interim analysis with 98 patients showed that the probability of reaching a statistically significant improvement in PFS by the end of the study was only 7%. This led the Independent Data and Monitoring Committee to recommend termination of patient enrollment. After a median of 21-month follow-up of all randomized patients (117 in total), PFS6m from randomization was 67.2% [95% confidence interval (CI) 53.6-77.7] with T + BEV and 55.2% (95% CI 41.5- 66.9) with E + BEV [hazard ratio (HR): 1.0, 95% CI 0.7-1.5, P = 0.998]. Median PFS from BEV initiation was 12.5 and 12.3 months in the T + BEV and E + BEV arms, respectively. In the T + BEV arm, taxane was prematurely stopped for the majority of patients (94.9%), mainly due to toxicity (49.2%). Updated data after 35 months' median follow-up showed death rates of 44% and 55% in T + BEV and E + BEV arms, respectively. Conclusion: In this trial, maintenance therapy with E + BEV in ER-positive, HER2-negative MBC patients with no evidence of progression after first-line T + BEV did not achieve longer PFS compared with continuation of T + BEV. [ABSTRACT FROM AUTHOR]

Background: For men with advanced castration-resistant prostate cancer (CRPC), several treatment options are available, including androgen receptor (AR) pathway inhibitors (abiraterone acetate, enzalutamide), taxanes (docetaxel, cabazitaxel) and the radionuclide (radium-223). However, cross-resistance is a clinically relevant problem. Platinum compounds have been tested in a number of clinical trials in molecularly unselected prostate cancer patients. Advances in CRPC molecular profiling have shown that a significant proportion of patients harbour DNA repair defects, which may serve as predictive markers for sensitivity to platinum agents. Objective: To systematically identify and analyse clinical trials that have evaluated platinum agents in advanced prostate cancer patients. Methods: PubMed was searched to identify published clinical trials of platinum agents in advanced prostate cancer. The PRIMSA statement was followed for the systematic review process. Identified trials are analysed for study design, statistical plan, assessments of anti-tumour activity and the potential value of predictive biomarkers. Results: A total of 163 references were identified by the literature search and 72 publications that met the selection criteria were included in this review; of these 33 used carboplatin, 27 cisplatin, 6 satraplatin, 4 oxaliplatin and 2 other platinum compounds. Overall, anti-tumour activity varies in the range of 10%-40% for objective response and 20%-70% for PSA decline ≥50%. Response seemed highest for the combinations of carboplatin with taxanes or oxaliplatin with gemcitabine. The interpretation of the clinical data is limited by differences in response criteria used and patient populations studied. Conclusion: Platinum compounds have moderate anti-tumour activity in molecularly unselected patients with advanced prostate cancer. Translational evidence of DNA repair deficiency should be leveraged in future studies to select prostate cancer patients most likely to benefit from platinum-based therapy. [ABSTRACT FROM AUTHOR]

Background: In recurrent head and neck squamous cell carcinoma ineligible for resection or irradiation, treatment aims primarily at symptom control and quality of life enhancement with an expected outcome of 6-12 months. Methods: In 2005, a male patient, born in 1944, with a second local recurrence of human papillomavirus negative tonsil cancer was enrolled in the EXTREME trial, and randomized to platinum/5-fluorouracil/cetuximab arm resulting in partial remission with progression-free survival of 12 months. The second-line systemic therapy comprised 5 cycles of 3-weekly docetaxel/cisplatin/5-fluorouracil regimen plus weekly cetuximab. Results: As confirmed on imaging and repeated biopsies, complete response was achieved with disease-free survival of 8 years and follow-up period of 12 years. Severe acute toxicities during the taxane-based chemotherapy plus cetuximab included grade 4 anorexia and grade 3 febrile neutropenia. Conclusions: Poor tumor differentiation, no weight loss, oropharyngeal location, white race, and particularly the induced complete response were most likely the key favorable prognostic factors in the reported patient. The possibility of a synergistic interaction between taxanes and cetuximab should be further explored. [ABSTRACT FROM AUTHOR]

Currently, the clinical utility of taxane-based drug formulations in castration-resistant prostate cancer (CRPC) is severely limited by acquired chemotherapy resistance, dose-limiting toxicities, and nonresponders. Therefore, approaches to improve taxane-based chemotherapy are desperately required. In this review, we highlight the strategies that aim to overcome these limitations, such as bypassing therapy resistance, targeted drug delivery, and adequate prediction of therapy response. The involvement of the apoptotic pathway, ABC transporters, the glucocorticoid receptor (GR) axis, androgen receptor (AR) splicing, epithelial plasticity, and cancer stem cells in mediating taxane-resistance are outlined. Furthermore, passive and active targeted nanomedicinal drug delivery strategies and the use of circulating tumor cells in predicting docetaxel responses are discussed. Finally, recent advances towards clinical translation of these approaches in CRPC are reviewed. [ABSTRACT FROM AUTHOR]

Aim To acquire patient characteristics, safety, relapse and survival outcomes of early-stage breast cancer patients receiving docetaxel (Taxotere(R))-based regimen in adjuvant setting from the Asia-Pacific region. Methods This was an open-label, international, longitudinal, multicenter, observational, prospective cohort of consecutive early breast cancer (EBC) patients with a high risk of recurrence being treated with various docetaxel-containing anthracycline and non-anthracycline adjuvant regimens during 2006−2013. Results In this study, 1542 patients were enrolled. Anthracycline-containing regimens were administered in 92% of patients, while 8% of patients received non-anthracycline-containing docetaxel-based regimens. The mean dose intensity of docetaxel was 25.8, 22.4 and 25.4 mg/m2/week among patients receiving docetaxel-based monotherapy, combination and sequential therapy, respectively. Adverse events were reported in 94.9% of patients (anthracycline vs non-anthracycline regimen; 95.1% vs 93.5%). Serious adverse events were reported in 12.6% of patients (12.4% vs 14.6%). Grade 4 neutropenia was reported in 25.2% of patients (24.7% vs 30.9%) and febrile neutropenia in 1.9% of patients (2% vs 0.8%). Only 7% of patients had a relapse or a second primary malignancy. At 5-year follow-up, there were 127 (8.3%) deaths (8.4% vs 6.5%). Conclusion The Asia-Pacific Breast Initiative-I registry highlights the important patient and treatment characteristics of EBC patients treated with adjuvant docetaxel chemotherapy from the Asia-Pacific region that will help physicians to understand the impact of different docetaxel treatments on the clinical outcomes in this population. [ABSTRACT FROM AUTHOR]

Background: Oxaliplatin and taxane-induced neurosensory toxicity is dose-limiting and mostly presents with acute symptoms that affect the activities of daily living and overall quality of life. The objective of the present study is to assess the relief of acute neuropathy with venlafaxine treatment during the chemotherapy period.Patients and Methods: In this retrospective case-control study, from January 2010 to February 2015, patients who experienced treatment with oxaliplatin and taxane-induced acute neurotoxicity were evaluated according to the NCI-CTCAE v. 4.03 grading scale. Neurotoxicity was evaluated using a numeric rating scale (NRS) for pain intensity and experienced relief under the treatment of venlafaxine and using a neuropathic pain symptom inventory scale (NPSI) for the style of complaints. Patients who were diagnosed as mildly depressed according to the HOST anxiety and depression scale and who had grade 1 to 3 sensory neurotoxicity based on the NCI-CTCAE v. 4.03 grading scale, and who also reported ≥ 4/10 on a NRS were eligible. The primary end point was the rate of more than 75 % symptomatic relief under venlafaxine treatment.Results: Two hundred six patients were included (82 % female, median age: 52.7 years). Most patients had breast, gynecologic, and colon cancer (93.4 %). Ninety-one patients who received venlafaxine and 115 patients as the control group were assessed for neurotoxicity every 3 weeks. Based on the NRS, a rate of more than 75 % symptomatic relief was 53.5, 58.3, and 45.2 % in venlafaxine arm versus 0, 0, and 0 % in the control arm in the first, second, and third visits, respectively. Side-effects of venlafaxine (n = 7) were grade 1-2 nausea/vomiting (3.2 %) and asthenia/somnolence (3.2 %) without grade 3-4 events.Conclusion: Venlafaxine has a significant clinical activity against taxane-oxaliplatin-induced acute neurosensory toxicity. [ABSTRACT FROM AUTHOR]

Objective Prognoses of ovarian cancer (OC) have improved with the paclitaxel-carboplatin regimen. However, it remains unclear which cases exhibit a genuine benefit from taxane or from platinum. We aimed to predict taxane and platinum sensitivity in OC via gene expression. Methods We identified differentially expressed genes in responsive and resistant cases from advanced OC biopsy expression dataset GSE15622, containing responses to paclitaxel or carboplatin monotherapy. These genes generated a scoring system for prediction of drug response by applying single-sample gene set enrichment analysis. Discriminative metrics termed the T-score and C-score were derived. Results High C-score levels were significant in responders compared to non-responders in a separate cisplatin treatment dataset (GSE18864, p = 0.043). High C-score groups also had significantly better progression-free survival in three OC datasets (The Cancer Genome Atlas, TCGA: p = 0.02; GSE9891: p = 0.03; GSE30161: p = 0.001). In two additional datasets of advanced OC, high T-scores could associate taxane and platinum regimens with better survival than non-taxane and platinum regimens (GSE9891: p < 0.0001; GSE3149: p = 0.045), whereas in cases with low T-scores, different chemotherapeutic regimens did not result in a significant difference. Assessing TCGA and GSE9891, T-scores were elevated in the C1/Mesenchymal subtype, whereas C-scores were elevated in the C5/Proliferative subtype and were lower in the C1/Mesenchymal subtype (p < 0.0001, respectively). C- and T-scores negatively correlated with each other, suggesting complementary roles of taxane and platinum. Conclusions Our proposal and finding of a scoring system that could predict platinum or taxane response could be useful to develop individualized treatments to ovarian cancer. [ABSTRACT FROM AUTHOR]