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International Cancer Conference Journal Apr 2024Hepatic arterial infusion chemotherapy (HAIC) for liver metastases (LMs) from breast cancer is not a standard of care, but its effectiveness in patients with extensive...
Anthracycline-based hepatic arterial infusion chemotherapy achieved 17 months of disease regression in a patient with breast cancer liver metastases resistant to multiple systemic chemotherapies.
Hepatic arterial infusion chemotherapy (HAIC) for liver metastases (LMs) from breast cancer is not a standard of care, but its effectiveness in patients with extensive LMs who cannot tolerate systemic therapy has been reported. Herein, we report a case of breast cancer LMs that were controlled by anthracycline-based HAIC. A 46-year-old woman with estrogen receptor-positive, human epidermal growth factor receptor 2-negative metastatic breast cancer who had multiple LMs and bone metastases underwent seven lines of systemic therapy (paclitaxel/bevacizumab for 38 months; letrozole, nivolumab/fulvestrant, eribulin, gemcitabine/vinorelbine, high-dose toremifene/abemaciclib, and capecitabine for 21 months in total). However, owing to its adverse effects and the continued progression of the LMs, systemic therapy was switched to HAIC (40 mg/body epirubicin on day 1, 4 mg/body mitomycin C on days 1 and 15, and 500 mg/body 5-fluorouracil on days 1, 8, and 15; 28-day courses). In response to HAIC, the LMs remarkably regressed and were controlled for 17 months without severe adverse effects. HAIC was stopped when multiple brain metastases arose, and the patient died 2 months later. This case suggests that HAIC is a reasonable option for patients with extensive LMs, even in the late stage of treatment. HAIC recipients should be carefully selected through multidisciplinary discussions as the survival benefits of HAIC over systemic treatment remain unclear. Our findings identify a potential window for the use of traditional chemotherapeutic agents such as anthracyclines. Novel strategies to improve drug delivery are warranted in the future.
PubMed: 38524659
DOI: 10.1007/s13691-024-00656-8 -
Journal of Medicinal Chemistry Mar 2024Inspired by the structure of dysoxylactam A (DLA) that has been demonstrated to reverse P-glycoprotein (P-gp)-mediated multidrug resistance (MDR) effectively, 61...
Inspired by the structure of dysoxylactam A (DLA) that has been demonstrated to reverse P-glycoprotein (P-gp)-mediated multidrug resistance (MDR) effectively, 61 structurally simplified cyclolipopeptides were thus designed and synthesized via an effective method, and their reversing P-gp-mediated MDR potentials were evaluated, which provided a series of more potent analogues and allowed us to explore their structure-activity relationship (SAR). Among them, a well-simplified compound, , with only two chiral centers that all derived from amino acids dramatically reversed drug resistance in KBV200 cells at 10 μM in combination with vinorelbine (VNR), paclitaxel (PTX), and adriamycin (ADR), respectively, which is more promising than DLA. The mechanism study showed that reversed the MDR of tumor cells by inhibiting the transport function of P-gp rather than reducing its expression. Notably, compound effectively restored the sensitivity of MDR tumors to VNR in vivo at a dosage without obvious toxicity.
Topics: ATP Binding Cassette Transporter, Subfamily B, Member 1; Drug Resistance, Neoplasm; Drug Resistance, Multiple; ATP Binding Cassette Transporter, Subfamily B; Doxorubicin; Cell Line, Tumor; Lipopeptides
PubMed: 38502936
DOI: 10.1021/acs.jmedchem.3c01920 -
Child's Nervous System : ChNS :... Jun 2024Pediatric diffuse intrinsic pontine glioma (DIPG) is a fatal disease associated with a median survival of < 1 year despite aggressive treatments. This retrospective...
PURPOSE
Pediatric diffuse intrinsic pontine glioma (DIPG) is a fatal disease associated with a median survival of < 1 year despite aggressive treatments. This retrospective study analyzed the treatment outcomes of patients aged < 18 years who were diagnosed with DIPG between 2012 and 2022 and who received different chemotherapy regimens.
METHODS
After radiotherapy, patients with DIPG received nimotuzumab-vinorelbine combination or temozolomide-containing therapy. When nimotuzumab was unavailable, it was replaced by vincristine, etoposide, and carboplatin/cyclophosphamide (VECC). Temozolomide was administered as a single agent or a part of the combination chemotherapy comprising temozolomide, irinotecan, and bevacizumab. Furthermore, 1- and 3-year overall survival (OS), progression-free survival (PFS), and median OS and PFS were analyzed.
RESULTS
The median age of 40 patients with DIPG was 97 ± 46.93 (23-213) months; the median follow-up time was 12 months. One and 3-year OS were 35.0% and 7.5%, respectively. Median OS was 12 months in all patients (n = 40), and it was 16, 10, and 11 months in those who received first-line nimotuzumab-vinorelbine combination (n = 13), temozolomide-based (n = 14), and VECC (n = 6) chemotherapy regimens, respectively (p = 0.360). One patient who received gefitinib survived for 16 months. Conversely, patients who never received radiotherapy and any antineoplastic medicamentous therapy (n = 6) had a median OS of 4 months.
CONCLUSION
Nimotuzumab-vinorelbine combination therapy prolonged OS by 6 months compared with temozolomide-containing chemotherapy, although the difference was not statistically significant.
Topics: Humans; Female; Child; Male; Brain Stem Neoplasms; Child, Preschool; Retrospective Studies; Antineoplastic Combined Chemotherapy Protocols; Adolescent; Antibodies, Monoclonal, Humanized; Diffuse Intrinsic Pontine Glioma; Temozolomide; Vinblastine; Infant; Treatment Outcome
PubMed: 38478066
DOI: 10.1007/s00381-024-06329-4 -
International Journal of Molecular... Feb 2024Alveolar rhabdomyosarcoma (ARMS), an invasive subtype of rhabdomyosarcoma (RMS), is associated with chromosomal translocation events resulting in one of two oncogenic... (Review)
Review
Alveolar rhabdomyosarcoma (ARMS), an invasive subtype of rhabdomyosarcoma (RMS), is associated with chromosomal translocation events resulting in one of two oncogenic fusion genes, or . ARMS patients exhibit an overexpression of the pleiotropic cytokine transforming growth factor beta (TGF-β). This overexpression of TGF-β1 causes an increased expression of a downstream transcription factor called SNAIL, which promotes epithelial to mesenchymal transition (EMT). Overexpression of TGF-β also inhibits myogenic differentiation, making ARMS patients highly resistant to chemotherapy. In this review, we first describe different types of RMS and then focus on ARMS and the impact of TGF-β in this tumor type. We next highlight current chemotherapy strategies, including a combination of the FDA-approved drugs vincristine, actinomycin D, and cyclophosphamide (VAC); cabozantinib; bortezomib; vinorelbine; AZD 1775; and cisplatin. Lastly, we discuss chemotherapy agents that target the differentiation of tumor cells in ARMS, which include all-trans retinoic acid (ATRA) and 5-Azacytidine. Improving our understanding of the role of signaling pathways, such as TGF-β1, in the development of ARMS tumor cells differentiation will help inform more tailored drug administration in the future.
Topics: Humans; Rhabdomyosarcoma, Alveolar; Transforming Growth Factor beta; Transforming Growth Factor beta1; Paired Box Transcription Factors; Epithelial-Mesenchymal Transition; Rhabdomyosarcoma; Oncogene Proteins, Fusion
PubMed: 38474036
DOI: 10.3390/ijms25052791 -
Cost Effectiveness and Resource... Mar 2024Triple-negative breast cancer (TNBC) is responsible for 10-20% cases of breast cancer and is resulting in rising healthcare costs. Thus, health-economic evaluations are...
BACKGROUND
Triple-negative breast cancer (TNBC) is responsible for 10-20% cases of breast cancer and is resulting in rising healthcare costs. Thus, health-economic evaluations are needed to relate clinical outcomes and costs of treatment options and to provide recommendations of action from a health-economic perspective.
METHODS
We investigated the cost-benefit-ratio of approved treatment options in metastatic TNBC in Germany by applying the efficiency frontier approach. These included sacituzumab-govitecan (SG), eribulin, vinorelbine, and capecitabine. Clinical benefit was measured as (i) median overall survival (mOS) and (ii) health-related quality of life (HRQoL) in terms of time to symptom worsening (TSW). To assess medical benefits, literature was systematically reviewed in PubMed for (i) and (ii), respectively. Treatment costs were calculated considering annual direct outpatient treatment costs from a statutory healthcare payer perspective. It was intended that both, (i) and (ii), yield an efficiency frontier.
RESULTS
Annual direct outpatient treatment costs amounted to EUR 176,415.21 (SG), EUR 47,414.14 (eribulin), EUR 13,711.35 (vinorelbine), and EUR 3,718.84 (capecitabine). Systematic literature review of (i) and statistical analysis resulted in OS values of 14.3, 9.56, 9.44, and 7.46 months, respectively. Capecitabine, vinorelbine, and SG are part of the efficiency frontier including OS. The highest additional benefit per additional cost was determined for vinorelbine, followed by SG. Systematic review of (ii) revealed that no TSW data of TNBC patients receiving vinorelbine were available, preventing the presentation of an efficiency frontier including HRQoL.
CONCLUSIONS
Vinorelbine is most cost-effective, followed by SG. Health-economic evaluations support decision-makers to assess treatment options within one indication area. In Germany, the efficiency frontier can provide decision support for the pricing of innovative interventions. Results of our analysis may thus guide reimbursement determination.
PubMed: 38459569
DOI: 10.1186/s12962-024-00528-1 -
Naunyn-Schmiedeberg's Archives of... Mar 2024The treatment of non-small cell lung cancer (NSCLC) is known as a significant level of unmet medical need in spite of the progress in targeted therapy and personalized...
The treatment of non-small cell lung cancer (NSCLC) is known as a significant level of unmet medical need in spite of the progress in targeted therapy and personalized therapy. Overexpression of the Na/K-ATPase contributes to NSCLC progression, suggesting its potentiality in antineoplastic approaches. Epi-reevesioside F, purified from Reevesia formosana, showed potent anti-NSCLC activity through inhibiting the Na/K-ATPase, leading to internalization of α1- and α3-subunits in Na/K-ATPase and suppression of Akt-independent mTOR-p70S6K-4EBP1 axis. Epi-reevesioside F caused a synergistic amplification of apoptosis induced by gefitinib but not cisplatin, docetaxel, etoposide, paclitaxel, or vinorelbine in both NCI-H460 and A549 cells. The synergism was validated by enhanced activation of the caspase cascade. Bax cleavage, tBid formation, and downregulation of Bcl-xL and Bcl-2 contributed to the synergistic apoptosis induced by the combination treatment of epi-reevesioside F and gefitinib. The increase of membrane DR4 and DR5 levels, intracellular Ca concentrations, and active m-calpain expression were responsible for the caspase-8 activation and Bax cleavage. The increased α-tubulin acetylation and activation of MAPK (i.e., p38 MAPK, Erk, and JNK) depending on cell types contributed to the synergistic mechanism under combination treatment. These signaling pathways that converged on profound c-Myc downregulation led to synergistic apoptosis in NSCLC. In conclusion, the data suggest that epi-reevesioside F inhibits the Na/K-ATPase and displays potent anti-NSCLC activity. Epi-reevesioside F sensitizes gefitinib-induced apoptosis through multiple pathways that converge on c-Myc downregulation. The data support the inhibition of Na/K-ATPase as a switch-on mechanism to sensitize gefitinib-induced anti-NSCLC activity.
PubMed: 38451282
DOI: 10.1007/s00210-024-03031-9 -
Targeted Oncology Mar 2024Sacituzumab govitecan (TRODELVY) is a first-in-class trophoblast cell-surface antigen 2 (Trop-2)-directed antibody and topoisomerase I inhibitor conjugate that is... (Review)
Review
Sacituzumab govitecan (TRODELVY) is a first-in-class trophoblast cell-surface antigen 2 (Trop-2)-directed antibody and topoisomerase I inhibitor conjugate that is approved globally as monotherapy for the treatment of adults with unresectable locally advanced or metastatic, hormone receptor-positive (HR+)/human epidermal growth factor receptor 2-negative (HER2-; defined as immunohistochemistry 0, 1+ or 2+ and in situ hybridization-negative) breast cancer who have received endocrine-based therapy and ≥ 2 additional systemic therapies in the advanced setting. In the phase III TROPiCS-02 trial, intravenous sacituzumab govitecan demonstrated statistically significant and clinically meaningful improvements in progression-free survival and overall survival compared with physician's choice of chemotherapy (capecitabine, eribulin, gemcitabine or vinorelbine) in adults with metastatic HR+/HER2- breast cancer. Sacituzumab govitecan had a generally manageable tolerability profile in these patients; the most common treatment-related grade ≥ 3 adverse events included neutropenia, diarrhoea, leukopenia, anaemia, fatigue and febrile neutropenia. Sacituzumab govitecan carries regulatory warnings for severe neutropenia and severe diarrhoea. Sacituzumab govitecan demonstrated an overall benefit in terms of health-related quality of life. Current evidence indicates that sacituzumab govitecan is an effective treatment option, with a generally manageable tolerability profile, for patients with pre-treated, unresectable locally advanced or metastatic HR+/HER2- breast cancer.
Topics: Adult; Humans; Female; Breast Neoplasms; Quality of Life; Camptothecin; Immunoconjugates; Neutropenia; Diarrhea; Antibodies, Monoclonal, Humanized
PubMed: 38446351
DOI: 10.1007/s11523-024-01036-1 -
Beilstein Journal of Nanotechnology 2024In this study, a multifunctional therapeutic agent combining chemotherapy and photothermal therapy on a single platform has been developed in the form of...
In this study, a multifunctional therapeutic agent combining chemotherapy and photothermal therapy on a single platform has been developed in the form of vinorelbine-loaded polydopamine-coated iron oxide nanoparticles. Vinorelbine (VNB) is loaded on the surface of iron oxide nanoparticles produced by a solvothermal technique after coating with polydopamine (PDA) with varying weight ratios as a result of dopamine polymerisation and covalent bonding of thiol-polyethylene glycol (SH-PEG). The VNB/PDA/FeO nanoparticles have a saturation magnetisation value of 60.40 emu/g in vibrating sample magnetometry, which proves their magnetisation. Vinorelbine, which is used as an effective cancer therapy agent, is included in the nanocomposite structure, and in vitro drug release studies under different pH conditions (pH 5.5 and 7.4) and photothermal activity at 808 nm NIR laser irradiation are investigated. The comprehensive integration of precise multifunctional nanoparticles design, magnetic response, and controlled drug release with photothermal effect brings a different perspective to advanced cancer treatment research.
PubMed: 38440320
DOI: 10.3762/bjnano.15.24 -
Anticancer Research Mar 2024Evidence supports that use of aripiprazole sensitizes drug-resistant oral cancer cells. The aim of the study was to investigate whether aripiprazole can achieve...
BACKGROUND/AIM
Evidence supports that use of aripiprazole sensitizes drug-resistant oral cancer cells. The aim of the study was to investigate whether aripiprazole can achieve sensitization of highly drug-resistant breast cancer cells, as well as identify its relevant mechanisms of action.
MATERIALS AND METHODS
MCF-7/ADR, KB, and KBV20C breast cancer cells were treated with aripiprazole, vincristine (VIC), vinorelbine, vinblastine and their combination. Cell viability assay, annexin V analyses, cellular morphology and density observation with a microscope, western-blotting, fluorescence-activated cell sorting (FACS), and analysis for P-gp inhibitory activity were performed to investigate the drugs' mechanism of action.
RESULTS
We found that high drug resistance in MCF-7/ADR cells results from high P-gp inhibitory activity via overexpression of P-gp. Aripiprazole reduced cell viability, increased G arrest, and upregulated apoptosis when used as a co-treatment with VIC. Furthermore, we demonstrated that co-treatment with vinorelbine and vinblastine increased the sensitization of MCF-7/ADR breast cancer cells to aripiprazole. We confirmed that VIC-aripiprazole combination has much higher sensitization effects than either VIC-thioridazine or VIC-trifluoperazine co-treatment in MCF-7/ADR cells, since the previously known bipolar drugs (thioridazine and trifluoperazine) has lower P-gp inhibitory activity. However, aripiprazole-induced sensitization was not observed in VIC-treated MDA-MB-231 breast cancer cells suggesting that combination therapy with aripiprazole is specific for P-gp-overexpressing drug-resistant breast cancer cells.
CONCLUSION
Co-treatment with low doses of aripiprazole sensitized MCF-7/ADR cells to VIC. Combination therapy with aripiprazole may be a valuable tool for delaying or reducing cancer recurrence by targeting P-gp-overexpressing drug-resistant breast cancer cells.
Topics: Humans; Female; Vincristine; ATP Binding Cassette Transporter, Subfamily B, Member 1; Aripiprazole; Vinorelbine; Breast Neoplasms; Vinblastine; MCF-7 Cells; Thioridazine; Trifluoperazine; Drug Resistance, Neoplasm; Cell Line, Tumor; ATP Binding Cassette Transporter, Subfamily B; Doxorubicin
PubMed: 38423668
DOI: 10.21873/anticanres.16900