Taxane Group Research Articles

Self-assembled nanoparticles of alginate and paclitaxel-triphenylphosphonium for mitochondrial apoptosis targeting.

Paclitaxel (PTX), an antimitotic drug from the taxanes group, prevents the proliferation of breast cancer cells through mitosis arrest and activation by a cascade of signaling pathways that lead to apoptosis. Mitochondria is one of the important signaling routes for inducing apoptosis. For mitochondria targeting, triphenylphosphonium (TPP) with a delocalized charge and hydrophobic nature was utilized as a moiety to facilitate penetration through a phospholipid membrane of mitochondria. PTX-TPP was synthesized via pH-sensitive ester bond between hydroxyl groups of PTX and carboxylic acid of (4-carboxybutyl) TPP. Then PTX-TPP prodrug encapsulated in alginate nanoparticles, which were self-assembled by the ionotropic complexation technique for enhancement of mitochondrial apoptosis in breast cancer cells. The loading of PTX-TPP conjugation in self-assembled alginate nanoparticles was 16.5% and the particle size of nanoparticles was 123nm with zeta potential around -25.8 Mv. The in vitro cytotoxicity and IC50 of PTX-TPP nanoparticles in the growth of MCF7 cancer cell increased 6.3-fold higher than free PTX. The early apoptotic cells and the late apoptotic/necrotic cells for PTX-TPP nanoparticles were 11.6 and 3.9-fold higher than free PTX. This study indicated this mitochondrial-targeted self-assembled nanoparticles can inhibit the tumor cell growth of breast cancer.

Pyrotinib plus taxanes or vinorelbine for human epidermal growth factor receptor 2-positive metastatic breast cancer: A prospective study.

e13004 Background: Pyrotinib in combination with capecitabine is recommended as the second-line treatment for human epidermal growth factor 2 (HER2)-positive metastatic breast cancer (MBC) in China. The efficacy and safety of pyrotinib combined with non-capecitabine chemotherapy regimens remain unclear. Thus, we conducted this study to evaluate the efficacy and safety of pyrotinib combined with taxanes or vinorelbine in HER2-positive MBC. Methods: Patients with HER2-positive MBC were included to receive pyrotinib combined with taxanes or vinorelbine in Jiangsu Cancer Hospital. Patients received pyrotinib 400mg orally once daily plus taxanes (docetaxel 75-100 mg/m2 on day1, or nab-paclitaxel 125 mg/m2 on days 1 and 8, paclitaxel 80 mg/m2 on days 1 and 8, every 3 week) or vinorelbine 25 mg/m2 on days 1 and 8, every 3 weeks. The primary endpoint was progression-free survival (PFS), and the secondary endpoints were objective response rate (ORR), disease control rate (DCR), clinical benefit rate (CBR), overall survival (OS) and safety. Results: Between Nov 20, 2018, and Jan 11, 2023, a total of 101 patients were assigned to pyrotinib plus taxanes group (n=83) and pyrotinib plus vinorelbine group (n=18). The median number of pyrotinib therapy lines was 2 (IQR 1-7), the first line accounted for 23.8%, the second line, and third line and above was 34.6%, 41.6%, respectively. As of May 24, 2023, the median PFS in the total was 11.5 months (95% confidence interval [CI], 8.8-15.7). The median PFS was significantly longer in the pyrotinib plus taxanes group than in the pyrotinib plus vinorelbine group, with median PFS being 12.2 months (95% CI, 9.2-18.6) and 8.4 months (95% CI, 5.5-13.7) (HR=2.2 [95% CI, 1.2-3.9]; P=0.005), respectively. The median PFS in the first-line, second-line, and third-line and above treatment was 28.6 (95% CI, 10.6-NA), 12.2 (95% CI, 8.5-16.3), and 8.3 months (95% CI, 6.3-14.5), respectively. The most common grade 3 or 4 adverse events were diarrhea (22.8%), leukopenia (19.5%), and neutropenia (18.2%). Conclusions: The median PFS of pyrotinib plus taxanes or vinorelbine, especially taxanes, was not inferior even superior to that of pyrotinib combined capecitabine. No increase treatment-related side effects was reported. Thus, the combination of pyrotinib and taxanes or vinorelbine regimen can be an option for HER2-positive MBC. Clinical trial information: ChiCTR2000041217.

Abstract PO3-28-05: Therapeutic Plasmapheresis as a Symptomatic Treatment for Paclitaxel-Associated Peripheral Polyneuropathy

Abstract Relevance: Paclitaxel-associated peripheral polyneuropathy (PIPN) is one of the most common side effects that develop during treatment with drugs of the taxane group. In the treatment of early breast cancer with paclitaxel 80 mg/m2 weekly, 12 injections, PINP develops in 90% of patients of varying severity. The main symptoms are pain and numbness in the arms and legs, which is associated with the accumulation of paclitaxel in the ganglia of the spinal cord, as well as increased expression in the ganglia of the spinal cord of chemokines and cytokines, such as IL-1β, IL-8 and TNF-α, as well as CXCR4, RAGE, CXCL1, CXCL12, CX3CL1 and C3. We hypothesized that the severity of PIPN symptoms can be reduced by lowering the concentration of chemokines and cytokines in the blood by performing plasmapheresis sessions. Research methods: An open prospective study was carried out, the protocol of which was approved by the ethical committee. The study included 30 patients (100% women) aged 30 to 60 years (mean age 45 years) who developed PIPN during paclitaxel therapy 80 mg/m2, weekly, 12 injections. The severity of PIPN symptoms was assessed using a “visual analogue scale” (VAS). The results of the VAS evaluation varied from 6 to 8 points. Patients underwent 5 courses of membrane plasmapheresis with exfusion of 400-500 ml of plasma per session (20 ml per 1 kg of body weight), plasma loss was compensated with saline. Repeated procedures were performed once every two months for 6 months. Results: 30 patients underwent 15 procedures of therapeutic plasmapheresis within 6 months. In 21 patients (70%) there was a pronounced decrease in PIPN symptoms (VAS - 2-3 points), in 3 patients (10%) a moderate decrease in symptoms (VAS -5-6 points), in 6 (20%) no effect of plasmapheresis (VAS - 7-8 points). Approximately 15% of procedures were associated with adverse events, the most common of which were vasovagal reactions; 20% of patients had at least one adverse event. Conclusions: Given the subjective reduction in the severity of PIPN symptoms during courses of therapeutic plasmapheresis in more than 70% of cases, therapeutic plasmapheresis can be used as a symptomatic therapy for PIPN, however, taking into account the subjective assessment of the results by patients, there may be a risk of developing cognitive errors. Therefore, this method of therapy requires more thorough study. Citation Format: Sardor Abdugafforov, Vladimir Vorotnikov, Alexander Soynov, Tornike Mchedlidze, Igor Kopytich, Sofia Kim. Therapeutic Plasmapheresis as a Symptomatic Treatment for Paclitaxel-Associated Peripheral Polyneuropathy [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO3-28-05.

Outcome and response rate in post neoadjuvant chemotherapy for breast cancer in a tertiary hospital in Malaysia

Background: The use of preoperative chemotherapy also increased the rate of breast conserving surgery in breast cancer. This study aims to assess the type of chemotherapy and biological markers that associated with pathological complete response in our population. Methods: This is a data analysis involving breast cancer patients confirmed pathologically that underwent neoadjuvant chemotherapy in Hospital Raja Perempuan Zainab II from January 2018 to December 2021. Retrospective sampling was done using Sistem Pengurusan Pesakit (SPP) which is a hospital-generated database. All patients were given standard chemotherapy regimens. Results: A total of 59 patients enrolled in this study. Half of the patients were luminal A (48%), luminal B and triple negative breast cancer (TNBC) were both 23%. All patients received antracyclin as neoadjuvant regime and 54% had a combination with Docetaxel. Only 1 patient achieved pCR which was TNBC, given Antracyclin + Taxane regime. Tumour reduction >90% highest in TNBC group and using FEC regime. Factors associated with survival were age and miller payne grade. The only pCR was achieved in triple negative breast cancer as being showed by previous study. Tumour loss with more than 30% is equal comparing Antracyline only group and Antracyline + Taxane group. Conclusions: Antracyline + Taxane regime chemotherapy is still the regime of choice for neoadjuvant chemotherapy in breast cancer. Triple negative breast cancer patients should receive preoperative chemotherapy as they will have a higher rate of pCR.

Luminal and basal subtyping of circulating tumor cells and influence on outcomes in patients with metastatic castration-resistant prostate cancer.

e17034 Background: Luminal and basal subtyping using PAM50 classifier and the prostate cancer classification system (PCS) have been shown to predict outcomes and treatment response in prostate cancer (PCa). However, these genomic classifiers rely on the acquisition of tumor samples, which are usually not available in patients with metastatic castration resistant PCa (mCRPC). Circulating tumor cells (CTC) are tumors cells shed into bloodstream and can serve as surrogates of tumor. In this study, we aimed to subtype circulating tumor cells with PAM50 and PCS classifiers and evaluate their prognostic performance in mCRPC patients. Methods: A CTC RNA assay was developed by combining NanoVelcro microfluidic system for enriching CTCs and Nanostring nCounter system for PAM50 and PCS profiling of CTCs. The PAM50 and PCS genes were refined through a bioinformatic pipeline to ensure the specific profiling of CTCs. The classification and prognostic performance of the refined CTC-PAM50 and CTC-PCS gene panels were validated in GenomeDx GRID database. For the clinical study, 50 blood samples from mCRPC patients before the initiation of androgen receptor signaling inhibitors (ARSI) (n = 34) or taxanes (n = 16) were analyzed with the CTC RNA assay. Kaplan-Meier analysis and log-rank test were used to evaluate the association between CTC-PAM50/PCS subtypes and survival. Results: The refined CTC-PAM50 (36 genes) and CTC-PCS (40 genes) classifiers retained their original classification and prognostic performance in the GenomeDx GRID cohort. In the clinical study, the CTC RNA assay classified the 50 mCRPC patients into luminal A (n = 14), luminal B (n = 22), and basal (n = 14) by CTC-PAM50 classifier; and PCS1 (n = 5), PCS2 (n = 24), and PCS3 (n = 21) by CTC-PCS classifier. Overall, patients assigned as PCS1 subtype had shorter overall survival than other subtypes (hazard ratio [HR] = 4.8). In addition, basal or PCS1 subtype showed worse biochemical progression free survival than other subtypes (ARSI group: Basal: HR = 2.5; PCS1: HR = 6.9. Taxanes group: Basal: HR = 5.0; PCS1: HR = 7.2). Conclusions: Luminal and basal subtyping of CTCs is prognostic and provides a noninvasive method for molecular profiling mCRPC patients.

Platinum/taxane/pembrolizumab vs platinum/5FU/pembrolizumab in patients with recurrent/metastatic (r/m) head and neck squamous cell carcinoma (HNSCC).

6039 Background: Pembrolizumab +/- chemotherapy is standard of care for patients (pts) with r/m HNSCC. Despite approval of platinum/5FU/pembrolizumab based upon the KN-048 study, a taxane is often substituted for 5FU due to ease of administration and tolerability. No studies have directly compared these approaches. We describe nationwide patterns of taxane vs 5FU chemoimmunotherapy in r/m HNSCC and compare survival and time on treatment between the two. Methods: This study used the nationwide Flatiron Health electronic health record (EHR)-derived de-identified database, and included pts treated with frontline pembrolizumab plus platinum-based chemotherapy (either taxane or 5FU) for r/m HNSCC. Demographic, cancer, and clinical outcomes were summarized. Categorical variables were compared using Pearson’s chi-square test; continuous variables were compared using T-test. Overall survival (OS) was estimated using Kaplan Meier methodology, and compared using log-rank test. Multivariable Cox regression for overall survival adjusting for age, sex, race, year of diagnosis, ECOG performance status (PS), smoking history, primary tumor site, PD-L1, HPV status, cisplatin use, socioeconomic status, insurance, and practice type was performed, with multiple imputation by chained equations for missing variables. Results: Of 444 pts, 321 (72%) received 5FU and 123 (28%) received taxane (108 paclitaxel, 15 docetaxel). Use of cisplatin rather than carboplatin was higher in the 5FU group than the taxane group (16.8% vs 4.9%, p=0.001). Taxane use was higher in academic vs community practices (50.7% vs 23.9%, p<0.001); within community sites, Northeast states had highest taxane use (27.5%) and Western states had lowest taxane use (16.7%). Pts with Medicare or Medicaid were more likely to receive taxane (35.5%) vs commercial (23.6%) or other (26.7%) insurance. OS did not differ between taxane and 5FU groups (mOS 12.7 vs 13.5 months, p=0.743). On multivariable Cox regression, HR for death associated with taxane vs 5FU was 1.01 (95%CI 0.73-1.41). HPV positive status was associated with improved survival (HR 0.58, 95%CI 0.40-0.83). PS>1 (HR 1.38, 95%CI 0.96-1.98) and cisplatin use (HR 1.37, 95%CI 0.95-1.98) showed non-significant trends towards worse survival. Taxane-treated pts received more treatment cycles (mean 11.3 vs 8.8 cycles, p=0.015) and were on treatment slightly longer (mean 6.9 vs 6.0 months, p=0.289) than 5FU-treated pts. Conclusions: In US pts with r/m HNSCC undergoing chemoimmunotherapy, rates of taxane vs 5FU use vary by academic setting, geographic region, and insurance status. There was no difference in survival between 5FU and taxane, and taxane-treated pts received more cycles of therapy. Platinum-taxane appears to be a non-inferior alternative to platinum-5FU with pembrolizumab for r/m HNSCC, and should be allowed in clinical trials.

Secondary Metabolism in Taxus spp. Plant Cell Culture In Vitro

The genus Taxus (yew) is a source of a number of high-value medicinal substances, particularly, paclitaxel (taxol)—a complex diterpenoid compound with a powerful antitumor action (trade name of Taxol®). Paclitaxel is one of the most efficient drugs in chemotherapy owing to its specific ability to suppress proliferation of tumor cells via stabilization of their microtubules. The world-wide demand for taxol is 800–1000 kg a year and these figures annually rise by 20%. The growing need for paclitaxel and its derivatives and the shortage of plant resources necessary for their production made compounds of the taxane group one of the most important objects for development of biotechnological methods of their production. Out of all the possible ways of taxol production (isolation from wild or plantation trees, total chemical synthesis or semisynthesis, use of yew cell cultures, techniques of metabolic engineering, and use of yew endophytic fungi), the most promising is industrial cultivation of Taxus spp. cell cultures. This review examines the papers dealing with investigation of secondary metabolism in dedifferentiated cells in vitro of various yew species and feasibility of industrial use of cell cultures for production of taxoids. We revealed a number of specificity of Taxus spp. cell cultures: (1) from a cytophysiological aspect—difficult initiation of cell cultures, their low growth characteristics, specific media and culturing conditions; (2) from a phytochemical aspect—distinction from intact plants in qualitative composition and content of secondary metabolites accounted for by specificity of cell culture as a biological system; predominant formation of С14-hydroxylated rather than of С13-hydroxylated taxoids; an opportunity for elevation of the content of taxoids—including commercially valuable ones (paclitaxel and baccatin III) with the aid of different tools (elicitation, stress exposures, two-phase cultivation and some others); (3) from a biotechnological aspect—possibility of industrial cultivation of yew cell cultures; existence of several successful industries (Germany and the Republic of Korea).

Secondary metabolism in <i>Taxus</i> spp. plant cell culture in vitro

The genus Taxus (yew) is a source of a number of high-value medicinal substances, particularly, paclitaxel (taxol)a complex diterpenoid compound with a powerful antitumor action (trade name of Taxol). Paclitaxel is one of the most efficient drugs in chemotherapy owing to its specific ability to suppress proliferation of tumor cells via stabilization of their microtubules. The world-wide demand for taxol is 8001000 kg a year and these figures annually rise by 20%. The growing need for paclitaxel and its derivatives and the shortage of plant resources necessary for their production made compounds of the taxane group one of the most important objects for development of biotechnological methods of their production. Out of all the possible ways of taxol production (isolation from wild or plantation trees, total chemical synthesis or semisynthesis, use of yew cell cultures, techniques of metabolic engineering, and use of yew endophytic fungi), the most promising is industrial cultivation of Taxus spp. cell cultures. This review examines the papers dealing with investigation of secondary metabolism in dedifferentiated cells in vitro of various yew species and feasibility of industrial use of cell cultures for production of taxoids. We revealed a number of specificity of Taxus spp. Cell cultures: (1) from a cytophysiological aspectdifficult initiation of cell cultures, their low growth characteristics, specific media and culturing conditions; (2) from a phytochemical aspectdistinction from intact plants in qualitative composition and content of secondary metabolites accounted for by specificity of cell culture as a biological system; predominant formation of С14-hydroxylated rather than of С13-hydroxylated taxoids; an opportunity for elevation of the content of taxoidsincluding commercially valuable ones (paclitaxel and baccatin III) with the aid of different tools (elicitation, stress exposures, two-phase cultivation and some others); (3) from a biotechnological aspectpossibility of industrial cultivation of yew cell cultures; existence of several successful industries (Germany and the Republic of Korea).

The Potential of Expression of Cyclin-D1 on Neoadjuvant Chemotherapy in Invasive Breast Carcinoma.

Patients undergoing neoadjuvant chemotherapy (NC) for invasive breast cancer (IBC) need indicators to track their progress during treatment. The goal of this research is to learn how cyclin D1 works in conjunction with taxane and non-taxane therapy for people with IBC. There were 31 examples divided into two groups, based on: those using a different type of NC (taxane- or non-taxane-based), and NC administration time (before or after). Tumor grade, age, PR, ER, Ki-67, HER2, and Cyclin D1 expression were among the factors considered. Using immunohistochemical labeling, we were able to categorize cyclin D1 levels according to a threshold value, and we supplemented this with data we found in our databases. To analyze the data, we used a modified linear model. The expression of Cyclin D1 decreased after NC delivery (p=0.086). Cyclin D1 expression was reduced in the taxane group (p=0.792). The non-taxane group also saw no differences in outcomes (p = 0.065). There was a larger decrease in Cyclin D1 expression in the non-taxane group compared to the taxane group, but the difference was not statistically significant (p=0.200). Cyclin D1 expression, even if the differences are not statistically significant, may be a prognostic indicator of NC reaction in IBC. The involvement of Cyclin D1 in NC warrants more research with bigger IBC sample sizes.

Anthracycline-containing and taxane-containing chemotherapy for early-stage operable breast cancer: a patient-level meta-analysis of 100 000 women from 86 randomised trials

Anthracycline-taxane chemotherapy for early-stage breast cancer substantially improves survival compared with no chemotherapy. However, concerns about short-term and long-term side-effects of anthracyclines have led to increased use of taxane chemotherapy without anthracycline, which could compromise efficacy. We aimed to better characterise the benefits and risks of including anthracycline, and the comparative benefits of different anthracycline-taxane regimens. We did an individual patient-level meta-analysis of randomised trials comparing taxane regimens with versus without anthracycline, and updated our previous meta-analysis of anthracycline regimens with versus without taxane, as well as analysing 44 trials in six related comparisons. We searched databases, including MEDLINE, Embase, the Cochrane Library, and meeting abstracts to identify trials assessing anthracycline and taxane chemotherapy. Adjuvant or neoadjuvant trials were eligible if they began before Jan 1, 2012. Primary outcomes were breast cancer recurrence and cause-specific mortality. Log-rank analyses yielded first-event rate ratios (RRs) and CIs. 28 trials of taxane regimens with or without anthracycline were identified, of which 23 were deemed eligible, and 15 provided data on 18 103 women. Across all 15 trials that provided individual data, recurrence rates were 14% lower on average (RR 0·86, 95% CI 0·79-0·93; p=0·0004) with taxane regimens including anthracycline than those without. Non-breast cancer deaths were not increased but there was one additional acute myeloid leukaemia case per 700 women treated. The clearest reductions in recurrence were found when anthracycline was added concurrently to docetaxel plus cyclophosphamide versus the same dose of docetaxel plus cyclophosphamide (10-year recurrence risk 12·3% vs 21·0%; risk difference 8·7%, 95% CI 4·5-12·9; RR 0·58, 0·47-0·73; p<0·0001). 10-year breast cancer mortality in this group was reduced by 4·2% (0·4-8·1; p=0·0034). No significant reduction in recurrence risk was found for sequential schedules of taxane plus anthracycline when compared with docetaxel plus cyclophosphamide (RR 0·94, 0·83-1·06; p=0·30). For the analysis of anthracycline regimens with versus without taxane, 35 trials (n=52 976) provided individual patient data. Larger recurrence reductions were seen from adding taxane to anthracycline regimens when the cumulative dose of anthracycline was the same in each group (RR 0·87, 0·82-0·93; p<0·0001; n=11 167) than in trials with two-fold higher cumulative doses of non-taxane (mostly anthracycline) in the control group than in the taxane group (RR 0·96, 0·90-1·03; p=0·27; n=14 620). Direct comparisons between anthracycline and taxane regimens showed that a higher cumulative dose and more dose-intense schedules were more efficacious. The proportional reductions in recurrence for taxane plus anthracycline were similar in oestrogen receptor-positive and oestrogen receptor-negative disease, and did not differ by age, nodal status, or tumour size or grade. Anthracycline plus taxane regimens are most efficacious at reducing breast cancer recurrence and death. Regimens with higher cumulative doses of anthracycline plus taxane provide the greatest benefits, challenging the current trend in clinical practice and guidelines towards non-anthracycline chemotherapy, particularly shorter regimens, such as four cycles of docetaxel-cyclophosphamide. By bringing together data from almost all relevant trials, this meta-analysis provides a reliable evidence base to inform individual treatment decisions, clinical guidelines, and the design of future clinical trials. Cancer Research UK, UK Medical Research Council.

Microsatellite instability and sex-specific differences of survival in gastric cancer after neoadjuvant chemotherapy without and with taxane: An observational study in real world patients

PurposeTo investigate the prognostic role of microsatellite instability (MSI) in association with sex of patients treated with platinum/fluoropyrimidine neoadjuvant chemotherapy (CTx) with or without a taxane-containing compound.MethodsOf the 505 retrospectively analyzed patients with gastric or gastroesophageal adenocarcinoma, 411 patients were treated without taxane and 94 patients with a taxane-containing compound. MSI was determined using standard assays.ResultsFemales demonstrated a better overall survival (OS) than males in the non-taxane group (HR, 0.59; 95% CI 0.41–0.86; p = 0.005), whereas no significant difference was found in the taxane group (HR 1.22; 95% CI 0.55–2.73, p = 0.630). MSI-High (-H) was associated with a better prognosis in both groups (without taxane: HR 0.56; 95% CI 0.33–0.97; p = 0.038; with taxane: HR 0.28; 95% CI 0.04–2.02, p = 0.204). In the non-taxane group, female MSI-H patients showed the best OS (HR 0.18, 95% CI 0.05–0.73; p = 0.016), followed by the female microsatellite stable (MSS) (HR 0.67, 95% CI 0.46–0.98, p = 0.040) and the male MSI-H group (HR 0.76; 95% CI 0.42–1.37, p = 0.760) taken the male MSS group as reference. In the taxane group, female and male MSI-H patients demonstrated the best OS (female MSI-H: HR 0.05, 95% CI 0.00–240.46; male MSI-H: HR 0.45, 95% CI 0.61–3.63, p = 0.438), whereas the female MSS group showed a decreased OS (HR 1.39 95% CI 0.62–3.12, p = 0.420) compared to male MSS patients.ConclusionOS in gastric/gastroesophageal cancer after CTx might depend on sex and MSI status and may differ between patients treated with or without a taxane compound in the chemotherapeutic regimen.

Efficacy and safety of nanoparticle-albumin-bound paclitaxel compared with conventional taxanes in women with breast cancer: a systematic review and meta-analysis

Long-term benefit of nanoparticle-albumin-bound paclitaxel (Nab-P) over conventional taxanes in breast cancer patients is still controversial. We conducted a systematic review of studies to identify the optimal taxanes for selection in clinical practice. We enrolled studies if they enrolled adults (age ≥18) with breast cancer, compared Nab-P (at any dose) to conventional paclitaxel or docetaxel, provided information on survival data, the response rate, or adverse events, were randomized controlled trials, case-control studies, or cohort studies, and were published in English (including those published online, ahead of the print publication). Cochrane Collaboration tool and Newcastle-Ottawa scale were used for bias-risk assessment. Grading of recommendations assessment, development, and evaluation approach were adopted for the quality of evidence evaluation. The outcomes included the overall response rate, pathological complete response rate, progression-free survival, overall survival, allergic reaction, leukopenia, neutropenia, and sensory neuropathy. A total of 20 eligible clinical studies comprising 11,046 patients were included in the analysis. No significant publication bias was observed based on a visual inspection of the funnel plots for progressionfree survival (PFS), and overall survival (OS). Compared to the conventional taxanes group (n=2,743), the Nab-P group (n=1,680) had a significantly higher ORR (RR =1.21, 95% CI: 1.07-1.37; P=0.003) and pCR (RR =1.33, 95% CI: 1.17-1.51; P<0.001). The Nab-P group also had a lower risk of disease progression and death than the conventional taxanes group (HR =0.89, P=0.269). Additionally, the Nab-P group had fewer treatment-related allergic reactions (RR =0.74, 95% CI: 0.59-0.93; P=0.009) and less grade ≥4 neutropenia (RR =0.39, 95% CI: 0.20-0.77; P=0.007) than the conventional taxanes group. The incidence of any-grade of neutropenia and sensory neuropathy were significantly higher in the Nab-P group than the conventional taxanes group (P=0.009 and P<0.001, respectively). The Nab-P in all stages of breast cancer patients had significantly better efficacy and tolerance than the conventional taxanes. Moreover, preventive strategies for reducing the incidence of Nab-P induced sensory neuropathy should be explored in future studies.

Outcomes of Triple-Negative Breast Cancer Patients in Response to Taxane and Nontaxane-Based Neoadjuvant Chemotherapies

Abstract Introduction Neoadjuvant chemotherapy (NAC) is the standard of care for locally advanced breast cancer. The achievement of pathological complete response (pCR) in response to NAC is of clinical significance as it correlates with improved long-term outcome. pCR rate varies with different chemotherapeutic agents and a higher rate may be associated with higher treatment cost and more toxicity.Triple-negative breast cancer (TNBC) has poorer prognosis than non-TNBC (estrogen receptor, progesterone receptor, and/or human epidermal growth factor receptor 2 expressing tumors), but patients achieving pCR may have similar outcome. We evaluated the response of TNBC after taxane and nontaxane-based NAC and its correlation with survival outcome. Materials and Methods This was a retrospective study comparing the efficacy of “taxotere, Adriamycin and cyclophosphamide TAC” versus “cyclophosphamide, epirubicin, 5-fluorouracil/cyclophosphamide, Adriamycin, 5-fluorouracil (CEF/CAF)” NAC regimens in patients with locally advanced TNBC. The efficacy and safety of both the regimens were compared. Overall and disease-free survival were analyzed. Results Two-hundred and forty-nine eligible patients were included and divided into two groups: taxane group receiving “TAC” regimen (123 patients) and nontaxane group receiving “CEF/CAF” regimen (126 patients). A higher pCR rate was achieved with taxane compared with nontaxane NAC (28 vs. 12%) (p = 0.0001). Although taxane addition did not lead to survival advantage for the entire group, significantly better survival rates were achieved for patients who had pCR compared with similar subgroup of patients in nontaxane group. Both the NAC regimens were well tolerable. Conclusion Taxane-based NAC was although costlier than anthracycline-based regimen but was more effective, resulting in a higher pCR rate and an improved survival outcome in patients who achieved pCR.

Exploring the Expression of Survivin on Neoadjuvant Chemotherapy in Invasive Breast Carcinoma

Background: Biomarkers are required to monitor the response to neoadjuvant chemotherapy (NC) in patients with invasive breast cancer (IBC). The purpose of this study is to determine the function of Survivin in the administration of NC, both taxane- and non-taxane-based, to patients with IBC.&#x0D; Methods: Thirty-one samples were categorized according to the NC's administrative status (before or after) and the type of NC used (taxane- or non-taxane-based). Age, tumor grade, receptor status (ER, PR, HER2, Ki-67), and survivin expression were evaluated. Survivin expressions were evaluated by IHC staining and categorized according median H-score cut-offs, while other data were collected from archives. Data was gathered and analyzed using generalized linear model. &#x0D; Results: Survivin expression decreased following NC administration, although not significantly (p=0.285). The taxane group had lower survivin expression. Statistically, this was not significant (p=0.329). The non-taxane group had the same outcome (p=0.792). The decline in survivin expression was greater in the taxane group than in the non-taxane group, although it was not statistically significant (p=0.369).&#x0D; Conclusion: Although the changes in survivin expression were not statistically significant, when clinical and laboratory data are analyzed, survivin expression has the potential to be a predictive biomarker of NC response as well as clinical outcome in IBC.

Determining the Effect of Reflexology on Nausea, Vomiting and Anxiety in Patients with Breast Cancer Receiving Chemotherapy: A Randomized Controlled Study

Aim: This study was conducted in a randomized controlled manner to evaluate the effect of reflexology on nausea, vomiting, and anxiety due to taxane group chemotherapeutics in patients with breast cancer. Method: The study was conducted in the Daytime Chemotherapy Unit of Gülhane Training and Research Hospital and Ankara Training and Research Hospital from June 28 to December 20, 2019, with intervention (n = 29) and control (n = 29) groups. Data were collected using the Patient Information Form, the Rhodes Index of Nausea, Vomiting and Retching, and the Spielberger State-Trait Anxiety Inventory. Patients in the intervention group received reflexology for a total of 6 weeks, once a week. The patients in the control group did not receive any treatment other than the routine maintenance of the chemotherapy unit. Result: As a result, it was determined that 40% of all patients were 55 years or older. While nausea was observed in all patients in the intervention and control groups, vomiting was not noted in the vast majority of patients. Regarding the effect of reflexology on nausea and vomiting, although the mean scores of nausea, vomiting and retching experience, occurrence and distress in both groups were lower than the initial measurement, there was no difference between the groups. Based on the research findings, the State and Trait Anxiety mean scores in the intervention group decreased significantly, while they increased in the control group. Conclusion: The research showed that while reflexology did not affect nausea and vomiting in breast cancer patients receiving chemotherapy, it was helpful in reducing anxiety.

Comparative analyses of paclitaxel/carboplatin with cisplatin/5-fluorouracil-based chemoradiation in locally advanced inoperable upper and middle third esophageal cancer: A randomized prospective pilot study.

Chemoradiation therapy (CRT) remains the treatment of choice for inoperable locally advanced esophageal cancer (LAEC). Several CRT regimens are existent in esophageal cancer, but definitive conclusions are lacking. We performed a pilot study to compare treatment outcome, survival, and toxicities in inoperable upper and middle third esophageal cancer patients undergoing CRT using either paclitaxel/carboplatin or cisplatin/5FU based regimen. Patients were randomised in two arms (arm A and arm B). In Arm A, taxane-based (Paclitaxel+carboplatin) and in arm B non-taxane-based (cisplatin+5FU) doublet chemotherapy drugs were given concurrently with external beam radiation therapy (EBRT). EBRT in two phases up to a total dose of 54 Gy/27#@2Gy/# was given. Response was subsequently assessed using Response evaluation criteria in solid tumors (RECIST v1.1) and toxicities utilizing Common Terminology Criteria for Adverse Events (CTCAE v 4.0). The overall response rate (ORR) in the taxane-based group was higher than the non-taxane-based group, but was not significantly different (p=0.851). Regarding hematological toxicities, anaemia and reduced cell counts were more in the taxane group compared to the non-taxane group while non-hematological toxicities were comparable. Similarly, better survival with late toxicities were seen with taxane-based arm when compared to non-taxane-based arm, though it was not statistically significant. Our pilot analysis highlights the fact that paclitaxel/carboplatin CRT shows better response, survival, and comparable toxicities when compared to cisplatin/5FU, though statistically nonsignificant. Further randomised prospective trials with large sample size are warranted.

PDL-1 Expression and Survival in Metastatic Non-small Cell Lung Cancer Patients Who Received Chemotherapy as First-Line Treatment.

To show the effect of programmed cell death protein-1ligand (PDL-1) level on survival times in patients with metastatic non-small cell lung cancer (mNSCLC) receiving chemotherapy, to determine the relationship between PDL-1 level, neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR). The data of 158 patients who received chemotherapy for mNSCLC were evaluated retrospectively. Clinical and demographic data, PDL-1 expression levels and follow-up periods of the patients were recorded. The patients were divided into 2 groups according to PDL-1 levels. In all patients, progression free survival (PFS) was 5.6 months and overall survival (OS) was 18.8 months. Patients with low PDL-1 had a longer PFS than patients with high PDL-1 (p:0.038). In the gemcitabine and taxane groups, patients with low PDL-1 had a longer PFS than patients with high PDL-1 (p:0.047). There was a significant correlation between NLR and PDL-1 levels. In the groups with high PDL-1, patients with low NLR levels had higher OS than patients with high NLR level (p:0.043). Also, there was a significant difference between the OS patients with low and high PLR levels (p:0.520). In patients with mNSCLC whose PDL-1 levels and NLR levels are low, immunogenic chemotherapies such as gemcitabine and taxane can be tried as an alternative treatment.

KANSER TEDAVİSİNDE KULLANILAN ANTİ-MİKROTÜBÜL İLAÇLARDAN VİNCA ALKALOİDLER VE PAKLİTAKSEL’İN DNA BAĞLANMA AKTİVİTELERİ

OBJECTIVE: Microtubules are an essential part of the intracellular cytoskeletal structure and possess unique polymerization dynamics that are critical for many cellular functions, including cell division. Anti-microtubule drugs that interfere with microtubule formation are important chemotherapeutic agents for the treatment of various cancer. These drugs that block mitosis seem to work by a common mechanism, which suppresses the dynamics of microtubules, slows cells, induces apoptosis and subsequently kills tumor cells. Vinca alkaloids (vinblastine, vincristine and vinorelbine) and Taxanes (paclitaxel) are two different classes of anti-microtubule drugs that cause microtubule dysfunction and inhibit cancer cell proliferation. The main activity of vinca alkaloids and taxanes result from their binding interactions with tubulin proteins. However, studies on DNA interactions of these anti-microtubule drugs are not sufficient. In this study, it was aimed to investigate the DNA binding activities of the vinca alkaloids (vinblastine, vincristine, vinorelbine) and paclitaxel.MATERIAL AND METHODS: The interactions of the drugs with DNA were analyzed by agarose gel electrophoresis assay. Three types of DNA were used in each experiment, including 100bp marker DNA, pUC19 plasmid DNA (2686 bp), and pBR322 plasmid DNA (4361 bp). After the DNAs were incubated with different concentrations of the drugs under certain conditions, agarose gel electrophoresis was performed. DNA band distributions were analyzed with a gel analysis system so that the drugs-DNA interactions could be interpreted.RESULTS: According to our results, it was found that among the vinca alkaloids, especially vinorelbine binds to DNA with higher activity than vincristine and vinblastine. The Vinca alkaloids have structural properties required for DNA binding activity and there is a similarity in their DNA binding models. However, the results showed that paclitaxel, which is from the taxane group, did not have DNA binding activity. This may be because the chemical structure of paclitaxel is not suitable for binding to DNA.CONCLUSIONS: The interaction of drugs with DNA play an important role in determining the pathways of drugs action and their ability to cause DNA damage. Consequently, the findings of our study will contribute to elucidating the effect mechanisms and the genotoxic potentials of these drugs, which are microtubule inhibitors.

PDL-1 Expression and Survival in Metastatic Non-small Cell Lung Cancer Patients Who Received Chemotherapy as First-Line Treatment

ObjectiveTo show the effect of programmed cell death protein-1 ligand level survival times in patients with metastatic non-small cell lung cancer receiving chemotherapy, to determine the relationship between programmed cell death protein-1 ligand level, neutrophil-to-lymphocyte ratio, and platelet-to-lymphocyte ratio.Material and MethodsThe data of 158 patients who received chemotherapy for metastatic non-small cell lung cancer were evaluated retrospectively. Clinical and demographic data, programmed cell death protein-1 ligand expression levels, and follow-up periods of the patients were recorded. The patients were divided into 2 groups according to programmed cell death protein-1 ligand levels. ResultsIn all patients, progression-free survival was 5.6 months and overall survival was 18.8 months. Patients with low programmed cell death protein-1 ligand had a longer progression-free survival than patients with high programmed cell death protein-1 ligand (P = .038). In the gemcitabine and taxane groups, patients with low programmed cell death protein-1 ligand had a longer progression-free survival than patients with high programmed cell death protein-1 ligand (P = .047). There was a significant correlation between neutrophil-to-lymphocyte ratio and programmed cell death protein-1 ligand levels. In the groups with high programmed cell death protein-1 ligand, patients with low neutrophil-to-lymphocyte ratio levels had higher overall survival than patients with high neutrophil-to-lymphocyte ratio level (P = .043). Also, there was a significant difference between the overall survival patients with low and high platelet-to-lymphocyte ratio levels (P = .520).ConclusionIn patients with metastatic non-small cell lung cancer whose programmed cell death protein-1 ligand levels and neutrophil-to-lymphocyte ratio levels are low, immunogenic chemotherapies such as gemcitabine and taxane can be tried as an alternative treatment.

Comparative Assessment of Platinum Salts and Taxane Group Hypersensitivity Reactions, The Role of Skin Tests in Diagnosis?

We aimed to investigate the role of skin tests (ST) in the diagnosis of hypersensitivity reactions (HSRs) with platinum salts (PS) and taxane (TX) groups drugs and their reliability in patient management. Patients' data who developed immediate HSR with PS and TX were recorded and ST was performed. The gradual challenge was applied to all patients with ST negative and grade 1-2 with the suspect drug. In total, the data of 104 patients (74 with PS, 30 with TX) who developed HSR against PS and TX were shared. The gradual challenge was applied to 72 ST negative and grade 1-2 patients (46 PS group, 26 TX group). The gradual challenge was negative in 39 patients in the PS group and 23 patients in the Tx group. The negative predictive value (NPV) for PS was 83% and NPV for TX was 88%. We found significantly higher skin test positivity in patients with PS and TX and grade 3 HSR (p = 0.007, p = 0.001). A significant correlation was found between skin test positivity and early onset of symptoms (p = 0.001 for PS, p = 0.015 for TX). In terms of symptoms witnessed in HSR, we observed the itching, urticaria, hypotension, syncope, and abdominal pain symptoms significantly more in the group with a positive skin test (p < 0.024, p < 0.001, p < 0.001, p < 0.002, and p < 0.025, respectively). We found very high NPV values for PS and TX. We found that the gradual challenge applied to patients with negative skin tests is reliable if Grade 3 HSR is not observed and with this approach, unnecessary desensitization processes and/or drug alterations can be avoided.