Administration Of Epirubicin Research Articles

Epirubicin and Non-Muscle Invasive Bladder Cancer Treatment: A Systematic Review.

(1) Background: Intravesical chemotherapy is the standard of care in intermediate-risk non-muscleinvasive bladder cancer (NMIBC). Different agents are used across the world based on availability, cost, and practice patterns. Epirubicin (EPI), one of these agents, has been used by many centers over many decades. However, its true differential efficacy compared to other agents and its tolerability are still poorly reported. We aimed to assess the differential efficacy and safety of intravesical EPI in NMIBC patients. (2) Methods: This study aimed to systematically review the efficacy and safety profile of Epirubicin (EPI) in the management of non-muscle invasive bladder cancer (NMIBC) compared to other adjuvant therapies. A systematic search of the PUBMED, Web of Science, clinicaltrials.gov, and Google Scholar databases was conducted on 31 December 2023, using relevant terms related to EPI, bladder cancer, and NMIBC. The inclusion criteria targeted studies that evaluated patients treated with EPI following the transurethral resection of bladder tumors (TURBT) for NMIBC and compared oncological outcomes such as recurrence and progression with other adjuvant therapies, including Mitomycin C (MMC), Gemcitabine (GEM), and Bacillus Calmette-Guérin (BCG). Additionally, studies investigating the safety profile of EPI administered intravesically at room temperature and under hyperthermia, as well as oncological outcomes associated with hyperthermic intravesical EPI administration, were included. (3) Results: Eleven studies reported adverse events after adjuvant intravesical instillations with EPI; the most frequently reported adverse events included cystitis (34%), dysuria, pollakiuria, hematuria, bladder irritation/spasms, fever, nausea and vomiting, and generalized skin rash (2.3%). Nine studies compared EPI to BCG in terms of recurrence and progression rates; BCG instillations showed a lower recurrence rate compared to EPI, with limited or non-significant differences in progression rates. Two studies found no significant differences between EPI and MMC regarding progression and recurrence rates. One study showed statistically significant lower recurrence and progression rates with GEM in high-risk NMIBC patients. Another study found no significant differences between EPI and GEM regarding recurrence and progression. (4) Conclusions: EPI exhibits similar oncological performances to Gemcitabine and Mitomycin C currently used for adjuvant therapy in NMIBC. Novel delivery mechanisms such as hyperthermia are interesting newcomers.

Abstract P116: Exploring The Cardioprotective Potential Of Roflumilast (pde-4 Inhibitor) Against Experimental Epirubicin-induced Cardiotoxicity.

Introduction: Cardiotoxicity is an important side effect of the treatment of a malignant tumour with Anthracyclines. The anthracycline family drug epirubicin (EPI) is one of the most potent chemotherapeutic agents for treating a range of solid and hematologic malignant tumours. However, its anti-tumor efficacy is dose-dependent, and the development of cardiac-toxicities limits its clinical use. In various Pharmacological Studies Roflumilast (ROF), a PDE-4 Inhibitor has been shown a Neuroprotective and Cardioprotective response but its role in EPI-induced cardiotoxicity and the underlying mechanisms has never been Evaluated. Hypothesis: The Study hypothesized that Roflumilast exerts cardioprotection against EPI-induced cardiotoxicity through attenuating cardiac mitochondrial dysfunction and inflammatory markers. Methods: Wistar rats of either sex were employed into 4 groups 3 groups comprised 7 animals while the control group had 5 animals, EPI-treated rats were intraperitoneally injected with 10 mg/kg for 1 day, while control rats were on normal diet. EPI+ROF (Low Dose) treated rats were intraperitoneally injected with 10 mg/kg of EPI for 1 day and 1mg/kg of ROF via oral gavage for 7 days. While in the higher dose of EPI+ROF treated rats were intraperitoneally injected with 10 mg/kg of EPI for 1 day and 2mg/kg of ROF via oral gavage for 7 days. The rat hearts were rapidly removed to determine cardiac mitochondrial functions and various cardiac biomarkers. Results: EPI induced significantly excessive mitochondrial Oxidative Stress, increased tissue TBARS and decreased levels of SOD and GSH. Conversely, a 7-day treatment with ROF (1mg/kg/day , p.o .) and ROF (2mg/kg/day, p.o .) significantly reduced TBARS levels while increasing SOD and GSH concentrations. The levels of TNF-α, CK-MB AST, ALT, and LDH were noted to be markedly increased in EPI-induced rats. While treatment with ROF (1mg/kg/day, p.o., 7 days ) and ROF (2mg/kg/day, p.o., 7 days) showed significantly decreased levels of TNF-α, CK-MB AST, ALT, LDH. Conclusion: In the current investigation, it can be concluded that administration of EPI leads to Oxidative Stress, Inflammation and Cardiotoxicity. Treatment with the ROF 2mg/kg showed cardioprotective potential by significantly decreasing inflammatory markers, oxidative stress parameters and cardiotoxic parameters. Our findings suggest that ROF protects the heart from EPI-induced cardiotoxicity, and it may serve as a guide for future cardioprotective research strategies.

Hypoxia-induced miR-181a-5p up-regulation reduces epirubicin sensitivity in breast cancer cells through inhibiting EPDR1/TRPC1 to activate PI3K/AKT signaling pathway

Breast carcinoma (BC) ranks as a predominant malignancy and constitutes the second principal cause of mortality among women globally. Epirubicin stands as the drug of choice for BC therapeutics. Nevertheless, the emergence of chemoresistance has significantly curtailed its therapeutic efficacy. The resistance mechanisms to Epirubicin remain not entirely elucidated, yet they are conjectured to stem from diminished tumor vascular perfusion and resultant hypoxia consequent to Epirubicin administration. In our investigation, we meticulously scrutinized the Gene Expression Omnibus database for EPDR1, a gene implicated in hypoxia and Epirubicin resistance in BC. Subsequently, we delineated the impact of EPDR1 on cellular proliferation, motility, invasive capabilities, and interstitial-related proteins in BC cells, employing methodologies such as the CCK-8 assay, Transwell assay, and western blot analysis. Our research further unveiled that hypoxia-induced miR-181a-5p orchestrates the regulation of BC cell duplication, migration, invasion, and interstitial-related protein expression via modulation of EPDR1. In addition, we identified TRPC1, a gene associated with EPDR1 expression in BC, and substantiated that EPDR1 influences BC cellular dynamics through TRPC1-mediated modulation of the PI3K/AKT signaling cascade. Our findings underscore the pivotal role of EPDR1 in the development of BC. EPDR1 was found to be expressed at subdued levels in BC tissues, Epirubicin-resistant BC cells, and hypoxic BC cells. The overexpression of EPDR1 curtailed BC cell proliferation, motility, invasiveness, and the expression of interstitial-related proteins. At a mechanistic level, the overexpression of hypoxia-induced miR-181a-5p was observed to inhibit the EPDR1/TRPC1 axis, thereby activating the PI3K/AKT signaling pathway and diminishing the sensitivity to Epirubicin in BC cells. In summation, our study demonstrates that the augmentation of hypoxia-induced miR-181a-5p diminishes Epirubicin sensitivity in BC cells by attenuating EPDR1/TRPC1 expression, thereby invigorating the PI3K/AKT signaling pathway. This exposition offers a theoretical foundation for the application of Epirubicin in BC therapy, marking a significant contribution to the existing body of oncological literature.

Single Early Intravesical Instillation of Epirubicin for Preventing Bladder Recurrence after Nephroureterectomy in Upper Urinary Tract Urothelial Carcinoma.

We aimed to assess the effectiveness of early single intravesical administration of epirubicin in preventing intravesical recurrence after radical nephroureterectomy for upper tract urothelial carcinoma. Patients with upper tract urothelial carcinoma who underwent radical nephroureterectomy between November 2018 and May 2022 were retrospectively reviewed. Intravesical epirubicin was administered within 48 hours if no evidence of leakage was observed. Epirubicin (50 mg) in 50 mL normal saline solution was introduced into the bladder via a catheter and maintained for 60 minutes. The severity of adverse events was graded using the Clavien-Dindo classification. We compared intravesical recurrence rate between the two groups. Multivariate analyses were performed to identify the independent predictors of bladder recurrence following radical nephroureterectomy. Epirubicin (n=55) and control (n=116) groups were included in the analysis. No grade 1 or higher bladder symptoms have been reported. A statistically significant difference in the intravesical recurrence rate was observed between the two groups (11.8% at 1 year in the epirubicin group vs. 28.4% at 1 year in the control group; log-rank p=0.039). In multivariate analysis, epirubicin instillation (hazard ratio [HR], 0.43; 95% confidence interval [CI], 0.20 to 0.93; p=0.033) and adjuvant chemotherapy (HR, 0.29; 95% CI, 0.13 to 0.65; p=0.003) were independently predictive of a reduced incidence of bladder recurrence. This retrospective review revealed that a single immediate intravesical instillation of epirubicin is safe and can reduce the incidence of intravesical recurrence after radical nephroureterectomy. However, further prospective trials are required to confirm these findings.

Ten-year clinical outcome, toxicity and compliance of dose-dense sequential adjuvant administration of cyclophosphamide & epirubicin followed by docetaxel in patients with early breast cancer: A hellenic cooperative oncology group observational study (HE 10/10) with concurrent investigation of significance of tumor infiltrating lymphocytes

BackgroundDose-dense sequential (dds) chemotherapy has changed the clinical outcome of patients with early breast cancer (BC). To investigate the impact of dose intensity (DI) in the adjuvant setting of BC, this observational trial (HE 10/10) was conducted assessing the long-term survival outcome, safety and toxicity of a currently widely used chemotherapeutic regimen. In addition, the prognostic significance of tumor infiltrating lymphocytes (TILs) and infiltrating CD8+ lymphocytes were also evaluated in the same cohort. Patients and methodsTotally, 1054 patients were prospectively enrolled in the current study with 1024 patients being eligible, while adequate tissue was available for 596 of them. TILs, CD8+ lymphocytes in intratumoral areas in contact with malignant cells (iCD8), CD8+ lymphocytes in tumor stroma (sCD8) as well as the total number of CD8+ lymphocytes within the tumor area (total CD8) were assessed by immunohistochemistry. ResultsWithin a median follow-up of 125.18 months, a total of 200 disease-free survival (DFS) events (19.5%) were reported. Importantly, the 10-year DFS and OS rates were 78.4% (95% CI 75.0–81.5) and 81.7% (95% CI 79.0–84.1), respectively. Interestingly, higher CD8+ T cells as well as TILs in the tumor microenvironment were associated with an improved long-term survival outcome. ConclusionsIn conclusion, this study confirms the significance of dds adjuvant chemotherapeutic regimen in terms of long-term survival outcome, safety and toxicity as well as the prognostic significance of TILs and infiltrating CD8+ lymphocytes in BC patients with early-stage disease.

Chemotherapy induced phlebitis experienced by women with breast cancer following administration of epirubicin using a volumetric infusion pump: an observational study.

To establish the incidence and severity of chemotherapy-induced phlebitis (CIP) following administration of epirubicin chemotherapy using a volumetric infusion pump (Hospira Plum 360), compared to a previous study of manual injection of epirubicin. Also the study aimed to gain insight into staff perceptions of ease of use and safety of infusion pump administration. An observational study of women with breast cancer (n=47) receiving epirubicin via volumetric infusion pump. Phlebitis was reported through a participant self-assessment questionnaire and graded by clinical assessment three weeks after each chemotherapy cycle. Staff perceptions were explored using questionnaires. Infusion pump administration delivered a significantly higher concentration of epirubicin (p<0.001), a significantly higher rate of grade 3 and 4 participant reported CIP between cycles (p=0.003) but demonstrated no significant difference in grade 3 and 4 CIP when assessed clinically three weeks after treatment (p=0.157). Peripheral epirubicin administration will result in severe CIP being experienced by a proportion of patients irrespective of whether infusion pump or manual injection method is used. Those at high risk of severe CIP should be informed of the risk and offered a central line. For those with a lower risk of severe phlebitis use of the infusion pump appears to be a safe option.

79P Ten-year clinical outcome, toxicity and compliance of dose-dense sequential adjuvant administration of cyclophosphamide & epirubicin followed by docetaxel in patients with early breast cancer: An observational study with concurrent investigation of significance of TILs

Dose-dense sequential (dds) chemotherapy has tremendously changed the clinical outcome of patients with early breast cancer (BC). To investigate the impact of dose intensity (DI) in the adjuvant setting of BC, this observational trial (HE 10/10) was conducted assessing the long-term survival outcome, safety and toxicity of a now widely used chemotherapeutic regimen consisting of 4 cycles of cyclophosphamide and epirubicin q2 weeks, followed by 4 cycles of docetaxel q3 weeks. In addition, the prognostic significance of tumor infiltrating lymphocytes (TILs) and infiltrating CD8+ lymphocytes were also evaluated in the same cohort. Totally, 1,054 patients were prospectively enrolled in the current study with 1,024 patients being eligible, while adequate tissue was available for 659 of them. TILs, CD8+ lymphocytes in intratumoral areas in contact with malignant cells (iCD8), CD8+ lymphocytes in tumor stroma (sCD8) as well as the total number of CD8+ lymphocytes within the tumor area (total CD8) were assessed by immunohistochemistry. Within a median follow-up of 125.18 months, a total of 200 disease-free survival (DFS) events (19.5%) were reported. The median DFS and overall survival (OS) had not been reached yet at the time of data cut-off for the analysis, while the 10-year DFS and OS rates were 78.4% (95% CI 75.0-81.5) and 81.7% (95% CI 79.0-84.1), respectively. The studied regimen was well tolerated with 94.7% of the patients completing the full course of adjuvant chemotherapy (8 cycles), while the rest of them discontinued the treatment, mainly due to non-fatal reasons. Only a very small percentage of patients faced clinically significant myelotoxicity. Interestingly, higher CD8+ T cells in the tumor microenvironment were associated with an improved long-term survival outcome. In conclusion, this study confirms the significance of dds adjuvant chemotherapeutic regimen in terms of long-term survival outcome, safety and toxicity as well as the prognostic significance of infiltrating CD8+ lymphocytes in BC patients with early stage disease.

Impact of neoadjuvant FLOT treatment of advanced gastric and gastroesophageal junction cancer following surgical therapy.

Therapeutic treatment for advanced-stage (T2-T4) gastroesophageal junction (GEJ) and gastric cancer involves neoadjuvant chemotherapy with subsequent surgical intervention. Neoadjuvant oncological treatment for GEJ and gastric cancer previously consisted of the intravenous administration of epirubicin, cisplatin and fluorouracil (ECF) or epirubicin, cisplatin and capecitabine (ECX) combination (Group 1). The new protocol (FLOT, F: 5-FU, L: leucovorin, O: oxaliplatin, T: docetaxel), included patients with resectable GEJ and gastric cancer who had a clinical stage cT2 or higher nodal positive cN+ disease (Group 2). Between 31 December 2008 and 31 October 2022, the effect of different oncological protocols in terms of surgical outcomes in cases of T2-T4 tumours were retrospectively evaluated. Results of randomly assigned patients from the earlier ECF/ECX protocol (n = 36) (Group 1) and the new FLOT protocol (n = 52) (Group 2) were compared. Effect of different neoadjuvant therapies on tumour regression, types of possible side effects, type of surgery, and oncological radicality of surgical procedures were analysed. When comparing the two groups, we found that in case of the FLOT neoadjuvant chemotherapy (Group 2, n = 52), complete regression was achieved in 13.95% of patients, whereas in the case of ECF/ECX (Group 1, n = 36), complete regression occurred in only 9.10% of patients. Furthermore, in the FLOT group, the mean number of lymph nodes removed was slightly higher (24.69 vs. 20.13 in the ECF/ECX group). In terms of the safety resection margin (proximal), no significant difference was found between the two treatment groups. Nausea and vomiting were the most common side effects. The occurrence of diarrhea was significantly higher in the FLOT group (p = 0.006). Leukopenia and nausea occurred more commonly with the old protocol (Group 1). The rate of neutropenia was lower following FLOT treatment (p = 0.294), with the lack of grade II and III cases. Anaemia occured at a significantly higher rate (p = 0.036) after the ECF/ECX protocol. As a result of the FLOT neoadjuvant oncological protocol for advanced gastro-esophageal junction and gastric cancer, the rate of complete tumour regression increased significantly. The rate of side effects was also appreciably lower following the FLOT protocol. These results strongly suggest a significant advantage of the FLOT neoadjuvant treatment used before surgery.

MORPHOLOGICAL CHANGES OF THE BLADDER WALL AS A RESULT OF THE ACTION OF EPIRUBICIN

Summary. Intravesical administration of chemopreparations is widely used in clinical practice and in experiments. However, there are practically no data on morphological changes during the action of chemotherapy drugs on the mucous membrane of the urinary bladder. Aim: to establish the patterns of morphological changes in the layers of the bladder wall during intravesical administration of epirubicin. Object and methods: the studies use white outbred rats (females, weight 200-250 g). Epirubicin was administered intravesically. Morphological changes of the bladder wall were assessed by light microscopy of fixed preparations of cells stained with hematoxylin and eosin after 2 hours; 3, 7 and 21 days after administration of the epirubicin. The obtained results were analyzed by the method of variational statistics. Results: the obtained data indicate significant disorders on the side of the bladder wall, namely atrophic changes and fibrosis of the submucosal base. Morphological changes indicated circulatory disorders in the vessels of the bladdemucous membrane and the submucosal base, which was accompanied by a significant nonspecific inflammatory reaction. Conclusions: obtained morphological and morphometric data indicate significant changes in the bladder wall of rats under the action of the chemotherapy drug epirubicin.

Four Genes Predictive for the Severity of Hematological Damage Reveal a Similar Response after X Irradiation and Chemotherapy.

Radiological and especially nuclear accidents and incidents pose a threat to populations. In such events, gene expression (GE) analysis of a set of 4 genes (FDXR, DDB2, POU2AF1, WNT3) is an emerging approach for early and high-throughput prediction of the later manifesting severity degrees of the hematological acute radiation syndrome (H-ARS). Validation of this gene set on radiation victims is difficult since these events are rare. However, chemotherapy (CTX) is widely used e.g., breast cancer patient treatment and pathomechanisms, as well as blood cell count changes are comparable among both exposure types. We wondered whether GE changes are similarly deregulated after CTX, which would be interpreted as a confirmation of our already identified gene set for H-ARS prediction after irradiation. We examined radiation-induced differential GE (DGE) of our gene set as a positive control using in vitro whole blood samples from ten healthy donors (6 females, 4 males, aged: 24-40 years). Blood was incubated in vitro for 8 h after X irradiation with 0 and 4 Gy (1 Gy/min). These data were compared with DGE measured in vivo in blood samples of 10 breast tumor CTX patients (10 females, aged: 39-71 years) before and 4 days after administration of cyclophosphamide and epirubicin. RNA was isolated, reverse transcribed and quantitative real-time polymerase-chain-reaction (qRT-PCR) was performed to assess DGE of FDXR, DDB2, POU2AF1 and WNT3 relative to the unexposed samples using TaqMan assays. After X irradiation, we found a significant upregulation (irrespective of sex) with mean fold changes of 21 (P < 0.001) and 7 (P < 0.001) for FDXR and DDB2 and a significant down-regulation with mean fold changes of 2.5 (P < 0.001) and 2 (P = 0.005) for POU2AF1 and WNT3, respectively. After CTX, a similar pattern was observed, although mean fold changes of up-regulated FDXR (6-fold, P < 0.001) and DDB2 (3-fold, P < 0.001) as well as down-regulated POU2AF1 (1.2-fold, P = 0.270) and WNT3 (1.3-fold, P = 0.069) appeared lower corresponding to less altered blood cell count changes observed after CTX compared to historic radiation exposure data. However, a subpopulation of CTX patients (n = 6) showed on average a significant downregulation of POU2AF1 (1.8-fold, P = 0.04) and WNT3 (2.1-fold, P = 0.008). In summary, the pattern of up-regulated GE changes observed in all CTX patients and down-regulated GE changes observed in a subgroup of CTX patients appeared comparable with an already identified gene set predictive for the radiation-induced H-ARS. This underlines the significance of in vivo GE measurements in CTX patients, employed as a surrogate model to further validate already identified radiation-induced GE changes predictive for the H-ARS.

Short term results of the FLOT neoadjuvant therapy on the surgical management of advanced gastro-oesophageal junction adenocarcinoma

Introduction. Recently the therapeutic treatment for advanced, stage T2-T4 gastro-oesophageal junction cancer and those adjacent to the regional lymph nodes involves neoadjuvant chemotherapy with subsequent surgical intervention. Method. Neoadjuvant oncological treatment for gastro-oesophageal junction cancer previously consisted of the intravenous administration of epirubicin, cisplatin and fluorouracil (ECF) or epirubicin, cisplatin and capecitabine (ECX) combination (Group I). In the course of the new protocol (FLOT-, F: 5-FU, L: leucovorin, O: oxaliplatin, T: docetaxel), patients were included with resectable gastro-oesophageal junction cancer who had a clinical-stage cT2 or higher nodal positive cN+ disease (Group II). Between 31st of December 2013 and 1st of June 2021 we retrospectively analyzed the effect of these FLOT oncological protocols in terms of surgical outcomes in cases of T2-T4 tumors (n= 9). We compared the results of the randomly assigned nine patients from earlier ECF/ECX protocol (Group I). We analyzed the effect of the different neoadjuvant therapy on tumor regression, and evaluated the types of possible side effects, type of surgery, and the oncological radicality of surgical procedures (number of removed regional lymph nodes, resection margins). Results. Comparing the two groups we found that in cases of FLOT neoadjuvant chemotherapy complete regression was achieved significantly a higher number like in earlier ECX/ECF therapy. Furthermore, the average number of removed lymph nodes, and the safety resection margins (distal, circumferential) no significant difference was found between the two groups. Neutropenia was the most frequently encountered side effect. Leukopenia, neutropenia and nausea occurred more frequently in cases of the old protocol (Group I). Conclusions. As a result of the FLOT neoadjuvant oncological protocol for advanced gastro-oesophageal junction cancer, the number of cases with complete tumor regression has significantly increased. The present results strongly suggest a significant advantage in favor of FLOT neoadjuvant treatment following surgery. The prevalence of side effects was also appreciably lower in cases of the FLOT protocol.

Intravesical adjuvant regimen of epitubicin for intermediate risk NMIBC: Feasability study from CC-AFU vessie

Mitomycin C is the gold standard intravesical adjuvant therapy for intermediate-risk non-muscle-invasive bladder cancer (NMIBC). Tensions in the supply of mitomycin have emerged in France since late 2019. The ANSM in agreement with the AFU proposed to use epirubicin, already available in other European countries in this indication. The objective of our study was to report the initial French experience with the use of epirubicin in adjuvant treatment of NMIBC. We undertook a French multicenter retrospective descriptive study to collect, from the centers of the members of the CC-AFU bladder, the clinico-pathological data of the patients, the indications, the modalities of use (dose, indication, circuit in the pharmacy) and the tolerance data of epirubicin. The impact of the COVID-19 epidemic on treatment interruptions was also identified. Of the 20 centers contacted, 5 (25%) had implemented the epirubicin administration protocol developed by the CC-AFU bladder subcommittee. A total of 61 patients were treated with endovesical instillations of epirubicin between November 2019 and November 2020 for NMIBC at a single dose of 50mg. A total of 61 patients (mean age 67 years, 64-77 years) were treated with epirubicin, of which 45 (73.8%) were male. The patients had intermediate-risk NMIBC in 88.5%, the rest had high-risk disease. Induction therapy without or with maintenance was planned for 48 (78.7%) and 13 patients (21.3%), respectively. The preparation and administration of epirubicin was similar to that of mitomycin: central pharmacy preparation for same-day dispensing with immediate outpatient instillation. Unlike mitomycin, urinary alkalinization was not required. Of the 498 total instillations scheduled, 345 were performed (69.3%). The COVID-19 epidemic significantly impacted epirubicin delivery: one patient could not start treatment (1.6%), 8 patients (13.1%) had to discontinue it permanently; the rest of the patients underwent delayed instillations (18%). Other causes of discontinuation included infectious complications (9.8%). No major toxicities were reported. The implementation of an adjuvant epirubicin treatment protocol presented a good feasibility with low toxicity, without modifying the organization of the patients' care pathway. In the context of unpredictable mitomycin shortage, epirubicin represents a good therapeutic alternative in the endovesical adjuvant treatment of intermediate-risk NMIBC. 3.

The morphological changes of the colonic goblet cells and mucin profile in oncohematological patients under Epirubicin-based chemotherapy.

Changes in the lining of the small intestine following chemotherapy have been extensively studied, although also occurs in the large intestine. The aim of this study was to assess the consequences of Epirubicin-based therapy on goblet cells (GCs) and mucus production on colonic mucosa, immediately and after short-time of chemotherapy administration to oncohematological patients, by clinical and histopathological analysis. We assessed the mucus production, composition, and distribution by Alcian Blue (pH 2.5)–Periodic Acid–Schiff (PAS) staining, alongside with the immunoexpression of mucin (MUC)2, MUC4 and inflammatory markers in a series of oncohematological patients, immediately and after short-time of Epirubicin-based chemotherapy cumulative therapy cessation. We showed that GCs number decrease slightly at 48 hours, while mucous secretion became mixed (with a few neutral) after three weeks. Overall, the secretion was increased immediately after the Epirubicin administration, due to the activation of inflammatory pathways, assessed by increased immunostaining of tumor necrosis factor-alpha (TNF-α) at 48 hours. The MUC2 and MUC4 showed a decreased immunoexpression at 48 hours after the Epirubicin administration compared to controls and partially restored three weeks after the cessation. Overall, it is highly plausible that all these key players revolve around the chemotherapy-induced mucositis in oncohematological patients and highlights the morphofunctional particularities of the GCs, which further modulates the clinical outcome of the patient.

An observational study of the effect of dilution and delivery speed on the development of phlebitis after epirubicin chemotherapy

Aim Epirubicin causes venous irritation when administered through a peripheral cannula. The aim of this study was to identify if the speed of administration and/or volume of 0.9% saline used during epirubicin administration influences the development of chemical phlebitis in patients with breast cancer.Method Perceptions of 27 chemotherapy nurses of how administration technique may influence development of chemical phlebitis were collated from a questionnaire. Between August 2017 and May 2018, 120 cycles of epirubicin were observed and administration speed and volume of saline used during administration were recorded. Phlebitis signs and symptoms were graded by staff using a phlebitis severity scale and patients completed a questionnaire.Results Most chemotherapy nurses believed that administering a large volume of fluid during epirubicin and flushing afterwards were helpful in preventing phlebitis, but there was no consensus on the benefits of rapid or slow infusion speeds. Observation data analysed using SPSS v24 demonstrated no significant influence on the severity of phlebitis for administration speed (P=0.617) or volume of saline (P=0.879). Administration pain was associated with a significantly higher incidence of phlebitis (P=0.001).Conclusion Ensuring a concentration of <3mg/mL could reduce the risk of pain during administration.

Epirubicin chemotherapy in women with breast cancer: Alternating arms for intravenous administration to reduce chemical phlebitis.

To establish whether using alternating arms for peripheral intravenous epirubicin administration affects the severity or duration of epirubicin-induced phlebitis. An observational study of women with breast cancer (n=237) in a UK Cancer Centre. Data were analysed after receiving three treatment cycles according to the arm used for epirubicin administration: same, alternating or mixed arm (two consecutive cycles in one arm and one in the alternate arm). Phlebitis severity was graded by clinical staff after each treatment; participants also self-reported symptoms during treatment and for up to 6months after. The alternating arm group experienced significantly less severe symptoms than the other arm use groups, 6% (4 of 64) compared with 34% (p<0.001, odds ratio: 0.13 (95% CI: 0.043-0.38) alternating arm compared with same arm group). The alternating arm group reported less pain (p=0.013), lower overall impact (p=0.009), lower effect on function (p=0.032) and shorter duration of symptoms (p=0.001) than the other arm use groups. Using alternating arms for peripheral administration of epirubicin significantly reduces the severity and duration of chemical phlebitis and is recommended to improve patient experience and reduce the need for central venous access devices.

A case of cerebral embolism induced by serious cardiac failure after repeated administration of trastuzumab and epirubicin

トラスツズマブは，ヒト上皮成長因子受容体2 型蛋白のモノクローナル抗体であり，エピルビシンはアントラサイクリン系抗生物質で，どちらも乳癌の治療に用いられる．今回，両者による高度な心不全が原因で脳塞栓を起こした症例を経験した．症例は50 歳，女性．乳癌で乳房全摘出術を受け，術後エピルビシン投与後にトラスツズマブ治療を受けていた．就寝中に息苦しさ，意識レベル低下，右片麻痺を呈し当院に搬送された．来院時，失語，右上肢麻痺を認め，MRI で左頭頂葉に新鮮梗塞，MRA で左M2 閉塞を認め，アルテプラーゼ投与で改善した．心エコーでLVEF(left ventricular ejection fraction)が23.8％と低値を示した．入院2 日目にJCS 200 まで意識レベル低下し，MRA で右M1 閉塞を認め，カテーテル血栓除去術でThrombolysis In Cerebral Infarction(TICI) 3 の再開通を得た．第16 病日にも脳塞栓を再発した．本症例は，両薬剤による高度な心不全が主な原因で脳塞栓を繰り返したと考えられ，稀な症例と思われた．

A novel aptamer-based DNA diamond nanostructure for in vivo targeted delivery of epirubicin to cancer cells

The clinical administration of epirubicin (Epi) in the treatment of cancer has been restricted, owing to its cardiotoxicity.

Dexrazoxane improves cardiac autonomic function in epirubicin-treated breast cancer patients with type 2 diabetes.

Objective:The study objective was to investigate the protective effects of dexrazoxane (DRZ) on the cardiac autonomic nervous system (ANS) activity in anthracycline-treated breast cancer patients with diabetes.Methods:A total of 110 early stage breast cancer patients with type 2 diabetes were divided randomly into 2 even groups: chemotherapy alone (Chemo) and chemotherapy + DRZ (Chemo + DRZ). All patients underwent adjuvant chemotherapy (80 mg/m2 epirubicin and 500 mg/m2 cyclophosphamide) for a total of 6 cycles with 21 days/cycle. The Chemo + DRZ group patients were treated intravenously with 800 mg/m2 DRZ 30 minutes prior to the administration of epirubicin, while the Chemo group patients were given saline. The cardiac ANS function was evaluated for each patient before and after 6 cycles of chemotherapy by resting heart rate (RHR) and heart rate variability (HRV), which was evaluated by both time and frequency domains.Results:Before and after chemotherapy, patients in both groups showed significant decreases in HRV indices and increases in RHR and the low-frequency/high-frequency ratio. There were no significant differences between Chemo and Chemo + DRZ groups in terms of RHR and HRV indices before chemotherapy; however, after chemotherapy, patients in the Chemo group had a higher average RHR and lower HRV indices compared with patients in the Chemo + DRZ group.Conclusion:DRZ protects the cardiac ANS in epirubicin-treated early stage breast cancer patients with diabetes.

Application of FLEEOX Preoperative Chemotherapy via Intra-arterial and Intravenous Administration in Treatment of Unresectable Locally Advanced Gastric Cancer

BackgroundThe prognosis of unresectable locally advanced gastric cancer is poor. We applied preoperative chemotherapy via intra-arterial and intravenous administration to convert an initially unresectable gastric cancer to a resectable cancer. MethodsFrom January 2005 to December 2010, 105 patients with unresectable locally advanced gastric cancer (T3-4N1-3M0) were selected for preoperative chemotherapy with 5-FU + leucovorin + etoposide + oxaliplatin + epirubicin (FLEEOX) regimen. 5-Fu (370 mg/m2) and leucovorin (200 mg/m2) were administered by intravenous infusion on days 1–5. Intra-arterial administration of etoposide (80 mg/m2), oxaliplatin (80 mg/m2), and epirubicin (30 mg/m2) was performed by Seldinger method on days 6 and 20, repeated two cycles. Patients who achieved partial response (PR) or complete response (CR) underwent D2 dissection, followed by four to six cycles of XELOX chemotherapy. The response rate, 1- and 3-year survival rate, and R0 resection rate were evaluated. ResultsThe response rate of preoperative chemotherapy was 78.1 % (82 of 105 patients), with 7 cases of CR and 75 cases of PR, respectively. After chemotherapy, a total of 78 patients (74.3 %) underwent surgery, and 67 cases achieved R0 resection (85.9 %). The 1- and 3-year overall survival (OS) rate of all 105 patients was 71.9 and 31.7 % (median survival time, 18 months). The 1- and 3-year OS rate among the 78 patients treated with chemotherapy plus surgery was 84.5 and 40 % (median survival time, 30 months). Patients treated with chemotherapy plus surgery had significantly longer OS times than patients who underwent chemotherapy alone (P < 0.01). ConclusionsPatients with unresectable gastric cancer may obtain a survival benefit from preoperative chemotherapy via intra-arterial and intravenous administration and subsequent surgery.

Abstract P1-12-02: Sequential versus concurrent administration of epirubicin and docetaxel as adjuvant chemotherapy in women with high-risk axillary lymph node negative early breast cancer. An interim analysis of a multicenter randomized study from the Hellenic oncology research group

Abstract Purpose: To compare the sequential versus the concurrent administration of epirubicin and docetaxel as adjuvant therapy in high risk axillary node negative women with early breast cancer. Patients and treatment: Women 18-75 years old with invasive breast adenocarcinoma surgically resected with no infiltrated axillary lymph nodes and absence of metastatic disease were randomized to receive 4 cycles of epirubicin 90mg/m2 followed by 4 cycles of docetaxel 75mg/m2 (sequential regimen) or 6 cycles of epirubicin 75mg/m2 followed by docetaxel 75mg/m2 (concurrent regimen). All chemotherapy cycles were administered every 21 days with prophylactic G-CSF support for days 3-10 only for the concurrent regimen. Stratification was based on menopausal status, tumor size and hormone receptor expression. By protocol amendment in 2008 women with HER2 positive tumors were excluded. The primary endpoint of the study was to compare the disease-free survival (DFS) at 5 years and 329 patients were scheduled to enroll on each arm. Results: Between 2001-2013, 658 women were randomized and received the sequential (n=329) or the concurrent (n=329) regimen. The median age was 53 and 52 years, premenopausal status 43.8% versus 44.1%, tumor size &amp;lt;2cm in 44.1% versus 44.4%, histological grade 3 tumor in 52% versus 53.5% and hormone receptor negative disease in 33.1% versus 37.4% of patients in the sequential and concurrent regimens, respectively. After a median follow up of 70.5 and 70 months, there were 29 (8.8%) versus 42 (12.8%) disease relapses (p=0.102) and 11 (3.3%) versus 19 (5.8%) deaths (p=0.135), in the sequential and concurrent arms, respectively. The median DFS has not yet been reached in either arm (p=0.053) and the 5-year DFS rates were 92.6% versus 88.2% for sequential and concurrent arms, respectively. Dose reduction was required in 1.2% versus 3% (p=0.001) of the treatment cycles in the sequential and concurrent arms, respectively. Toxicity included grade 2-4 neutropenia in 54% versus 41% (p=0.001), febrile neutropenia 2.7% versus 6.1% (p=0.06), anemia 12% versus 17% (p=0.07), nausea/vomiting 18.5% versus 12.4% (p=0.03) of patients in the sequential and concurrent arms, respectively. There were no toxic deaths. Conclusion: In this interim analysis both the efficacy and the toxicity profile seem to favor the sequential over the concurrent regimen. Citation Format: Mavroudis D, Saloustros E, Boukovinas I, Papakotoulas P, Kakolyris S, Ziras N, Christophylakis C, Kentepozidis N, Timotheadou E, Rigas G, Varthalitis I-I, Kalbakis K, Agelaki S, Georgoulias V. Sequential versus concurrent administration of epirubicin and docetaxel as adjuvant chemotherapy in women with high-risk axillary lymph node negative early breast cancer. An interim analysis of a multicenter randomized study from the Hellenic oncology research group. [abstract]. In: Proceedings of the Thirty-Eighth Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2015 Dec 8-12; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(4 Suppl):Abstract nr P1-12-02.