epirubicin

The phase 3 PANTHER trial (NCT00798070) compared adjuvant sequential epirubicin/cyclophosphamide (EC) and docetaxel (D) administered in either tailored dose-dense (tDD EC/D) or standard interval schedule (FEC/D) to patients with high-risk resected early breast cancer (n = 2003). We could not reliably identify any subgroup not benefiting from dose-dense treatment, which should be considered for patients with primary resected high-risk breast cancer. Cancerfonden, Bröstcancerförbundet, Radiumhemmets Forskningsfonder, Amgen, Roche, sanofi-aventis.

P3, N=2017, Active, not recruiting, Karolinska University Hospital | Unknown status --> Active, not recruiting | Trial completion date: Jan 2022 --> Jan 2028

Carbonic anhydrase IX inhibitor, protoporphyrin IX (Por) complexed with Fe and epirubicin (EPI) are grafted to hyaluronic acid (HA) via disulfide bonds to obtain HSPFE and loaded xCT inhibitor SAS for fabricating SAS@HSPFE which is actively targeted to deep hypoxic tumor cells, and explosively releasing EPI, Por-Fe complex and SAS due to at high GSH concentration...SAS@HSPFE NPs revealed highly efficient antitumor effect in vivo study. This study provides a novel approach to cancer treatment by targeting redox imbalance.

Hormonal or endocrine therapy includes selective estrogen receptor modulators (SERMs) such as raloxifene, tamoxifen and toremifene, selective estrogen-receptor degraders (SERDs) including elacestrant and fulvestrant, and aromatase inhibitors such as anastrozole, letrozole, and exemestane...These agents include taxanes (docetaxel, nab-paclitaxel, and paclitaxel), anthracyclines (doxorubicin, epirubicin), anti-metabolites (capecitabine, gemcitabine, fluorouracil, methotrexate), alkylating agents (carboplatin, cisplatin, and cyclophosphamide), and drugs that target microtubules (eribulin, ixabepilone, ado-trastuzumab emtansine). Patients with ER-positive tumors are treated with 5-10 years of endocrine therapy and chemotherapy. For patients with metastatic breast cancer, standard first-line and follow-up therapy options include targeted approaches such as CDK4/6 inhibitors, PI3K inhibitors, PARP inhibitors, and anti-PDL1 immunotherapy, depending on the tumor type and molecular profile.

To investigate any causal relation between in utero chemotherapy exposure and fetal toxicity, late-gestation pregnant BL6 mice were exposed to vehicle, or one of six chemotherapeutic compounds, used to treat pregnant cases: cyclophosphamide, carboplatin, cisplatin (alkylating agents), epirubicin, doxorubicin (anthracyclines) or paclitaxel (taxane). Moderate toxicity was seen after in utero exposure to anthracyclines and taxanes. These findings emphasize the importance of investigating fetal toxicity in the clinical setting.

P2, N=30, Recruiting, First Affiliated Hospital of Zhejiang University

P1, N=448, Not yet recruiting, Hansoh BioMedical R&D Company

P2, N=44, Recruiting, Zhejiang Cancer Hospital | Not yet recruiting --> Recruiting

P2, N=200, Not yet recruiting, Peking University Shenzhen Hospital

Similar scaffold commercial drugs leucal (LEU), epirubicin (EPI), and lometrexol also displayed strong binding to the active site of MTHFD2...The interaction of breast cancer serum with high expression of MTHFD2 also showed an increase in binding of epirubicin in the presence of leucovorin...Further experimental studies are required to establish the potential mode of inhibition of the novel small ligands. Future in vivo trials may validate the effectiveness of the combinatorial therapy.

Furthermore, 48 women with luminal/HER2-low (IHC 2+/FISH-negative) high-risk EBC are enrolled to receive neoadjuvant pyrotinib plus chemotherapy (epirubicin-cyclophosphamide followed by docetaxel). In conclusion, neoadjuvant pyrotinib plus chemotherapy has encouraging efficacy and manageable toxicity in women with luminal/HER2-low (IHC 2+/FISH-negative) high-risk EBC. This regimen warrants to be further validated.

Also, we utilized epirubicin-sensitive (parental) and rpirubicin-resistant (EPIR) breast cancer cell lines to explore the role of RHAMMM in breast cancer progression...In addition, the knockdown of RHAMM significantly altered the expression of N-cadherin and E-cadherin, leading to an epithelial phenotype. Aberrant RHAMM signaling were considered to cause chemoresistance related to cancer stemness and epithelial to mesenchymal transition, and increased cell proliferation and migration of both chemo-sensitive and chemo-resistant breast cancer cells.

P2, N=30, Recruiting, First Affiliated Hospital of Zhejiang University | N=50 --> 30 | Trial completion date: Oct 2029 --> Jun 2029 | Initiation date: Oct 2024 --> Jun 2024 | Trial primary completion date: Oct 2026 --> Jun 2026

In a recent clinical trial, a new super-agonist complex of IL-15 - N803, has shown promising results when used in combination with BCG to treat patients with bladder cancer who do not respond to BCG. Moreover, the sequential intravesical instillation of epirubicin (EPI), a first-line bladder cancer drug, followed by thermally activated 15&15Rα@VNP, could achieve further improved therapeutic responses, without causing significant side effects. Therefore, this study shows that 15&15Rα@VNP can be effectively used in the treatment of bladder cancer and can be used as a complementary therapy to chemotherapy agents, promising for potential clinical translation in bladder cancer treatment.

P2/3, N=4936, Active, not recruiting, West German Study Group | Trial completion date: Oct 2024 --> Jan 2025

P2, N=35, Recruiting, First Affiliated Hospital of Zhejiang University

P=N/A, N=5, Completed, Lishui Central Hospital; Lishui Central Hospital

P2, N=86, Completed, UNICANCER | Active, not recruiting --> Completed

P2, N=44, Not yet recruiting, Zhejiang Cancer Hospital

P2, N=140, Recruiting, Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University | Trial primary completion date: Dec 2023 --> Dec 2025

P2, N=416, Completed, Palleos Healthcare GmbH | Active, not recruiting --> Completed

P2, N=74, Not yet recruiting, Second Affiliated Hospital, School of Medicine, Zhejiang University

A combination of serum albumin ≤ 3.8 g/dL, PT ≤ 80%, and largest tumor diameter ≥ 3.8 cm can predict the immediate deterioration of the Child-Pugh classification from A to B following TACE.

On the basis of this case and a comprehensive literature review, we recommend that clinicians consider the possibility of undifferentiated embryonal sarcoma of the liver in patients presenting with non-specific clinical and serological markers, particularly when there is inconsistency between ultrasound and computed tomography imaging findings, along with elevated 18F-fluorodeoxyglucose uptake observed in both the cystic wall and lesion on positron emission tomography-computed tomography examination. Given the rarity and high-grade malignancy of undifferentiated embryonal sarcoma of the liver, heightened clinical awareness and recognition are crucial for early diagnosis and successful therapy.

Neoadjuvant treatment in both study arms consisted of Atezolizumab 1200 mg every 3 weeks in addition to neoadjuvant CTX (12 x Carboplatin/Paclitaxel q1w followed by 4x Epirubicin/Cyclophosphamide q3w), in arm A preceded by an Atezolizumab monotherapy window of 840 mg once two weeks prior to initiation of combination therapy. To our knowledge our analysis is the largest prospective dataset regarding patients with eTNBC and low tumor burden treated with neoadjuvant chemotherapy and an immune checkpoint inhibitor. No significant differences were seen between treatment arms although numerically PD-L1 positive patients showed increased benefit from the immune therapy window. pCR rates were higher compared to the overall study population which may be attributed particularly to smaller tumor size.

ROC Plot analysis found that CSNK2A1 was a weak classifier of pathological complete response to FAC (fluorouracil, doxorubicin, and cyclophosphamide) (Area under curve, AUC = 0.651, p < 0.001) and FEC (fluorouracil, epirubicin, and cyclophosphamide) (AUC = 0.648, p < 0.001). This study demonstrates that CK2 subunit expression associates with a variety of clinical tumor characteristics, response to therapy, and prognosis in patients with breast cancer. CK2 may be useful as a prognostic biomarker and therapeutic target in breast cancer and warrants further exploration.

Neoadjuvant treatment in both study arms consisted of Atezolizumab 1200 mg every 3 weeks in addition to neoadjuvant CTX (12 x Carboplatin/Paclitaxel q1w followed by 4x Epirubicin/Cyclophosphamide q3w), in arm A preceded by an Atezolizumab monotherapy window of 840 mg once two weeks prior to initiation of combination therapy. In this analysis, the association between PD-L1 (IC) status and pCR rates could be reproduced in a subgroup of patients with =/> cT2 and/or N+ tumors. These results are in line with exploratory results of the NeoTRIP trial and the IMPASSION031 trial demonstrating an association of PD-L1 status with pCR rates after neoadjuvant Atezolizumab + chemotherapy in patients with high risk eTNBC similar to the population in this subgroup analysis. Our analysis in the largest group of patients with high risk eTNBC treated with neoadjuvant Atezolizumab + chemotherapy published to date demonstrated a significant association of PD-L1 status and pCR rates.

Pts were randomized 2:2:1 to: (A) HER3-DXd 5.6 mg/kg every (Q) 21 days (D) for 6 cycles; (B) HER3-DXd plus QD LET (+/- LHRH agonist); (C) CT with 4 cycles of EC/AC (epirubicin 90 mg/m2 or doxorubicin 60 mg/m2 and cyclophosphamide 600 mg/m2 Q14 or 21 D) followed by weekly paclitaxel 80mg/m2 for 12 weeks. In SOLTI VALENTINE, treatment with HER3-DXd, with or without LET, resulted in similar pCR rates to CT, while exhibiting a lower incidence of grade ≥3 TEAEs. CelTIL score at C2D1 correlated with response to HER3-DXd, but not to CT. The ongoing translational analysis, as well as the survival outcomes of VALENTINE, will provide further insights into the activity of HER3-DXd in EBC and clarify its potential role as a treatment strategy for high-risk HR+/HER2-neg breast cancer.

Background Neo-CheckRay (NCT03875573) demonstrated high rates of pathological complete response (pCR) after immune-modulating stereotactic body radiation therapy (iSBRT) to the primary BC in combination with the anti-PD-L1 durvalumab (durva) in high-risk early-stage luminal BC...Pts were randomized 1:1:1 to ARM 1: paclitaxel q1w x12 with iSBRT at week 4 (3x8 Gy targeting the primary tumour, avoiding lymph nodes and normal breast tissue), followed by dose-dense epirubicin/cyclophosphamide q2w x4; ARM 2 : arm 1 + durva q4w x5; and ARM 3 : arm 1 + durva + oleclumab (anti-CD73) q2w x4 then q4w x3...Table: 2O All Arm 1 Arm 2 Arm 3 n 135 45 45 45 pts, % B: PD-L1 negative* 58.5 57.8 57.8 60.0 W6: no tumor 32.2 13.5 46.3 34.9 W6: TILs increase 14.0 16.2 12.2 14.0 W6: PD-L1 IC increase 42.7 31 48 48 pCR rate, % All pts 28.9 17.8 33.3 35.6 B: PD-L1 negative* 24.0 3.8 34.6 33.3 W6: no tumor 48.7 40.0 47.4 53.3 W6: TILs increased 17.6 0.0 20.0 33.3 W6: PD-L1 IC increased 24.0 0.0 46.0 40.0 TILs: pts, % B: TILs ≥ 1% 51.5 51.2 50.0 53.3 W6: TILs ≥ 1% 26.8 28.1 27.3 25.0 PD-L1: pts, % B: PD-L1 IC ≥ 1% 57.0 57.8 57.8 55.6 W6: PD-L1 IC ≥ 1% 70.5 48.3 85.7 82.1 B: PD-L1 TC ≥ 1% 22.2 24.4 17.8 24.4 W6: PD-L1 TC ≥ 1% 29.9 13.8 42.9 37.0 B: PD-L1 CPS ≥ 1% 39.3 37.8 40.0 40.0 W6: PD-L1 CPS ≥ 1% 54.5 37.9 66.7 63.0 B, baseline; pts, patients; W6, week 6. *Stratification factor.Conclusions In pts treated with iSBRT+durva, PD-L1 increase or absence of tumor at W6 is associated with higher pCR rate at surgery.

In conclusion, anthracycline followed by docetaxel improved outcome compared with DC in patients with TOP2A normal early breast cancer, and no clinical value of TOP2A testing was shown. The risk of HF was doubled in patients receiving anthracycline; however, overall, the risk of HF was low.

Additionally, the aronia extract enhanced the responsiveness to epirubicin in both cancer cell lines...The utilization of the antitumor effects of aronia in clinical practice is still minimal and requires precise and long-term clinical evaluations. Individualized cancer-type profiling and patient stratification are crucial for effectively implementing plant nutraceuticals within targeted anti-cancer strategies in clinical oncology.

The patient received neoadjuvant chemotherapy with epirubicin and cyclophosphamide, followed by docetaxel, trastuzumab, and pertuzumab...A liver biopsy following treatment with trastuzumab emtansine (T-DM1) and trastuzumab deruxtecan (T-Dxd) revealed HER2-negative status. Cyclin-dependent kinase (CDK) 4/6 inhibitor combination endocrine therapy has been continued for 16 months to date while maintaining tumor shrinkage. It is essential to perform a rebiopsy during treatment to optimize therapy based on the subtype.

P3, N=204, Completed, Peking Union Medical College Hospital | Unknown status --> Completed | N=400 --> 204 | Trial primary completion date: Dec 2014 --> Dec 2023

In addition, patients with low NRGs scores were considerably more sensitive to vinorelbine, cyclophosphamide, epirubicin, gemcitabine, paclitaxel, 5-fluorouracil, docetaxel, and cisplatin. Moreover, qRT-PCR results confirmed that LEF1 had a higher expression level in tumor samples compared to normal samples, whereas NRG1 and STX11 exhibited lower expression levels in tumor samples than in normal samples. These results suggest that NRGs might be utilized as biomarkers to predict the prognosis of individuals with IBC, thereby paving the way for the creation of customized therapies for IBC.

Our study demonstrated that Epi might be used as a HDAC1 inhibitor. Low-dose Epi could inhibit tumor progression by inducing cell ferroptosis in vitro and in vivo. Thus, Epi administration with lower concentration may be much more favorable and safer in the treatment with leukemia.

LDHA may play a potential contributory role in PCa initiation and development, bone metastasis, and chemoresistance. LDHA is a key target for the treatment of PCa.

P=N/A, N=14, Not yet recruiting, Fudan University

P3, N=120, Not yet recruiting, West China Hospital

These findings were verified in a mouse xenograft model and are consistent with the expression patterns in human bladder cancer patients. Overall, these findings establish the role of lncRNA UCA1 in lipid metabolism and bladder cancer cell resistance to epirubicin, suggesting that lncRNA UCA1 may serve as a candidate target for enhancing bladder cancer chemotherapy.

P4, N=130, Completed, German Breast Group | Recruiting --> Completed | Trial completion date: Mar 2023 --> Aug 2024 | Trial primary completion date: Mar 2023 --> Aug 2024

For patients with pCR, the differences in EFS (log-rank p = 0.47) and OS (log-rank p = 0.38) were not statistically significant among the three groups, and the EFS (log-rank p = 0.59) and OS (log-rank p = 0.14) of non-pCR patients in the PLD group were similar to those in the epirubicin and pirarubicin groups. PLD had a similar therapeutic response and prognosis compared to epirubicin or pirarubicin in NAC for patients with HR ⩽ 10%/HER2 negative breast cancer, which means that PLD represents a potential NAC option.

Targeting the SRC-Slug-TGFβ2 axis may therefore lead to better treatment options and improve patient outcomes in this highly aggressive subpopulation of TNBCs.