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Gland Surgery May 2024In the past few years, the combination of trastuzumab and paclitaxel has become an important option for human epidermal growth factor receptor-2 (HER2)-positive breast...
The efficacy and safety of trastuzumab and albumin-bound paclitaxel with or without pyrotinib as neoadjuvant therapy for HER2-positive breast cancer: a prospective observational cohort study.
BACKGROUND
In the past few years, the combination of trastuzumab and paclitaxel has become an important option for human epidermal growth factor receptor-2 (HER2)-positive breast cancer. Small molecule tyrosine kinase inhibitors (TKIs) can bring clinical benefit to HER2-positive breast cancer patients. However, the efficacy and safety of these two regimens have not been compared. This study explored the efficacy and safety of pyrotinib combined with trastuzumab and albumin-bound paclitaxel (nab-paclitaxel).
METHODS
Patients with newly diagnosed HER2-positive early or locally advanced breast cancer treated at The Tumor Hospital of Mudanjiang City from November 2020 to June 2022 were included. The control group received pertuzumab in combination with nab-paclitaxel, whereas the pyrotinib group received pyrotinib in combination with pertuzumab and nab-paclitaxel as treatment, in a 3-week cycle for 4 cycles. The primary endpoints of this study were total pathological complete response (tpCR) rate, breast pathological complete response (bpCR) rate, and the secondary endpoints included progression-free survival (PFS), objective response rate (ORR), and the occurrence of adverse events (AEs).
RESULTS
A total of 72 patients were enrolled in the study and completed the study treatment. Baseline characteristics were well balanced between these two arms. In the control group, the tPCR rate was 23.68%, and the bpCR rate was 47.36%. In the pyrotinib group, the tPCR rate was 47.06%, and the bpCR rate was 64.71%. The tPCR rate in the pyrotinib group was significantly higher than that in the control group (P=0.049). The ORR in the pyrotinib group (67.65%) was significantly higher than that in the control group (42.11%, P=0.04 ). The median PFS (mPFS) for the control group was 9.24 months, with a mean PFS of 10.01±0.44 months [95% confidence interval (CI): 9.14-10.88 months]. In the pyrotinib group, mPFS was 9.74 months, with a mean PFS of 11.25±0.29 months (95% CI: 10.67-11.82 months). The PFS in the pyrotinib group was significantly longer than that in the control group (P=0.045). Safety results showed that the overall incidence of AEs in the control group was 68.42%, with a 3-grade adverse reaction rate of 21.05%. In the pyrotinib group, the overall incidence of AEs was 79.41%, with a 3-grade adverse reaction rate of 29.41%. The difference between the two groups was not statistically significant (P>0.05).
CONCLUSIONS
Pyrotinib group in neoadjuvant treatment for HER2 positive breast cancer has obvious short-term efficacy advantages over control group. This treatment regimen can prolong PFS for 1 year, and the safety during medication is controllable. This study still has some limitations, with the relatively small sample size and relatively short follow-up period, and a further large-scale, multicenter, randomized controlled trial is necessary to verify the clinical value of this dual-target treatment regimen.
PubMed: 38845840
DOI: 10.21037/gs-24-81 -
International Journal of Pharmaceutics:... Jun 2024This study aimed to present findings on a paclitaxel (PTX)-loaded polymeric micellar formulation based on polycaprolactone-vitamin E TPGS (PCL-TPGS) and evaluate its in...
This study aimed to present findings on a paclitaxel (PTX)-loaded polymeric micellar formulation based on polycaprolactone-vitamin E TPGS (PCL-TPGS) and evaluate its in vitro anticancer activity as well as its in vivo pharmacokinetic profile in healthy mice in comparison to a marketed formulation. Micelles were prepared by a co-solvent evaporation method. The micelle's average diameter and polydispersity were determined using dynamic light scattering (DLS) technique. Drug encapsulation efficiency was assessed using an HPLC assay. The in vitro cytotoxicity was performed on human breast cancer cells (MCF-7 and MDA-MB-231) using MTT assay. The in vivo pharmacokinetic profile was characterized following a single intravenous dose of 4 mg/kg to healthy mice. The mean diameters of the prepared micelles were ≤ 100 nm. Moreover, these micelles increased the aqueous solubility of PTX from ∼0.3 μg/mL to reach nearly 1 mg/mL. While the PTX-loaded micelles showed an in vitro cytotoxicity comparable to the marketed formulation (Ebetaxel), drug-free PCL-TPGS micelles did not show any cytotoxic effects on both types of breast cancer cells (∼100% viability). Pharmacokinetics of PTX as part of PCL-TPGS showed a significant increase in its volume of distribution compared to PTX conventional formulation, Ebetaxel, which is in line with what was reported for clinical nano formulations of PTX, i.e., Abraxane, Genexol-PM, or Apealea. The findings of our studies indicate a significant potential for PCL-TPGS micelles to act as an effective system for solubilization and delivery of PTX.
PubMed: 38845681
DOI: 10.1016/j.ijpx.2024.100253 -
Cardio-oncology (London, England) Jun 2024To understand how body composition in those with elevated body mass index impacts left ventricular function decline during cancer treatment, we determined the...
BACKGROUND
To understand how body composition in those with elevated body mass index impacts left ventricular function decline during cancer treatment, we determined the association between baseline body mass index (BMI), intra-abdominal adipose tissue (IAT) and subcutaneous adipose tissue (SAT) with baseline to 3-month left ventricular ejection fraction (LVEF) change among women receiving potentially cardiotoxic chemotherapy for breast cancer, lymphoma, or sarcoma.
METHODS
Women underwent potentially cardiotoxic chemotherapy, such as doxorubicin, cyclophosphamide, paclitaxel, and trastuzumab, for treatment of breast cancer, lymphoma, or sarcoma. We obtained magnetic resonance images (MRIs) of body composition and cardiac function prior to treatment, and then a repeat MRI for cardiac function assessment at three months into treatment. Analyses and assessment of abdominal adipose tissue volumes and LVEF outcomes were conducted by independent reviewers blinded to all patient identifiers. A general linear model was created to examine associations between adipose tissue depots, BMI, and 3-month LVEF change.
RESULTS
Women (n = 210) aged 56 ± 11 years with breast cancer, lymphoma, and sarcoma were enrolled (n = 195, 14, 1 respectively). Baseline BMI, IAT, and SAT fat were independently associated with 3-month LVEF declines (p = 0.001 to 0.025 for all). After adjusting for baseline cardiovascular disease risk factors, BMI, IAT, and SAT, BMI remained the only variable associated with 3-month LVEF decline (p = 0.047).
CONCLUSIONS
These results suggest that factors other than abdominal adipose tissue or traditional cardiovascular risk factors may contribute to 3-month declines in LVEF among women with elevated BMI receiving potentially cardiotoxic chemotherapy. Further investigation should be conducted on psychosocial stress, physical activity, sleep, or diet.
TRIAL REGISTRATION
DETECTIV_NCT01719562, WF99112, & WF97415-NCT02791581.
PubMed: 38845066
DOI: 10.1186/s40959-024-00233-1 -
Scientific Reports Jun 2024This study introduces a novel approach for synthesizing a Cu(II)-based coordination polymer (CP), {[Cu(L)(4,4´-OBA)]·HO}n (1), using a mixed ligand method. The CP was...
This study introduces a novel approach for synthesizing a Cu(II)-based coordination polymer (CP), {[Cu(L)(4,4´-OBA)]·HO}n (1), using a mixed ligand method. The CP was successfully prepared by reacting Cu(NO)·3HO with the ligand 3,6-bis(benzimidazol-1-yl)pyridazine in the presence of 4,4´-HOBA, demonstrating an innovative synthesis strategy. Furthermore, a novel hydrogel composed of hyaluronic acid (HA) and carboxymethyl chitosan (CMCS) with a porous structure was developed for drug delivery purposes. This hydrogel facilitates the encapsulation of CP1, and enables the loading of paclitaxel onto the composite to form HA/CMCS-CP1@paclitaxel. In vitro cell experiments demonstrated the promising modulation of thyroid cancer biomarker genes S100A6 and ARID1A by HA/CMCS-CP1@paclitaxel. Finally, reinforcement learning simulations were employed to optimize novel metal-organic frameworks, underscoring the innovative contributions of this study.
Topics: Paclitaxel; Copper; Hydrogels; Humans; Thyroid Neoplasms; Chitosan; Cell Line, Tumor; Hyaluronic Acid; Coordination Complexes; Drug Carriers; Metal-Organic Frameworks
PubMed: 38844812
DOI: 10.1038/s41598-024-63940-w -
Signal Transduction and Targeted Therapy Jun 2024Metastatic pancreatic cancer (mPC) has a dismal prognosis. Herein, we conducted a prospective, multicentre, single-arm, phase II trial evaluating the efficacy and safety...
First-line penpulimab (an anti-PD1 antibody) and anlotinib (an angiogenesis inhibitor) with nab-paclitaxel/gemcitabine (PAAG) in metastatic pancreatic cancer: a prospective, multicentre, biomolecular exploratory, phase II trial.
Metastatic pancreatic cancer (mPC) has a dismal prognosis. Herein, we conducted a prospective, multicentre, single-arm, phase II trial evaluating the efficacy and safety of penpulimab and anlotinib in combination with nab-paclitaxel/gemcitabine (PAAG) in patients with first-line mPC (NCT05493995). The primary endpoints included the objective response rate (ORR) and disease control rate (DCR), while secondary endpoints encompassed progression-free survival (PFS), overall survival (OS), and safety. In 66 patients analysed for efficacy, the best response, indicated by the ORR, was recorded at 50.0% (33/66) (95% CI, 37.4-62.6%), with 33 patients achieving partial response (PR). Notably, the DCR was 95.5% (63/66, 95% CI, 87.3-99.1%). The median PFS (mPFS) and OS (mOS) were 8.8 (95% CI, 8.1-11.6), and 13.7 (95% CI, 12.4 to not reached) months, respectively. Grade 3/4 treatment-related adverse events (TRAEs) were reported in 39.4% of patients (26/66). In prespecified exploratory analysis, patients with altered SWI/SNF complex had a poorer PFS. Additionally, low serum CA724 level, high T-cell recruitment, low Th17 cell recruitment, and high NK CD56dim cell scores at baseline were potential predicative biomarkers for more favourable efficacy. In conclusion, PAAG as a first-line therapy demonstrated tolerability with promising clinical efficacy for mPC. The biomolecular findings identified in this study possess the potential to guide the precise clinical application of the triple-combo regimen.
Topics: Humans; Male; Pancreatic Neoplasms; Female; Paclitaxel; Middle Aged; Aged; Deoxycytidine; Gemcitabine; Indoles; Albumins; Quinolines; Antineoplastic Combined Chemotherapy Protocols; Prospective Studies; Adult; Neoplasm Metastasis; Angiogenesis Inhibitors; Antibodies, Monoclonal, Humanized; Programmed Cell Death 1 Receptor
PubMed: 38844468
DOI: 10.1038/s41392-024-01857-6 -
Respiratory Medicine and Research Apr 2024Studies have shown improvement in overall survival with anti-PD1/PD-L1 molecules in combination with cisplatin/carboplatin and etoposide as a first-line treatment for...
Study design and rationale for IFCT- 2203 TAXIO: A study that aims to evaluate the effectiveness of a first-line chemotherapy regimen without etoposide, combined with durvalumab, for patients with extensive disease small cell lung cancer.
BACKGROUND
Studies have shown improvement in overall survival with anti-PD1/PD-L1 molecules in combination with cisplatin/carboplatin and etoposide as a first-line treatment for Small Cell Lung Cancer (SCLC). However, first-line efficacy remains limited and well below that observed in Non-Small Cell Lung Cancer (NSCLC). Etoposide may have a detrimental effect on lymphocyte activation, which could explain the limited benefit of immunotherapy in the first line and the lack of benefit in the second line for patients previously exposed to high levels of etoposide.
METHODS
We initiated a multicenter, single-arm, open-label phase II study of a chemotherapy regimen with durvalumab, combined with carboplatin and paclitaxel for extensive disease SCLC. Eligible patients will receive durvalumab plus carboplatin and paclitaxel every 3 weeks for up to 4 cycles, followed by durvalumab every 4 weeks until progression or unacceptable toxicity. A total of 67 patients will be enrolled in this study, with a 12-month enrollment period and 36-month follow-up. The primary endpoint is Overall Survival (OS) rate at 12 months. Secondary endpoints are best response rate, OS, OS at 24- and 36 months, progression free survival (PFS), duration of response, quality of life and safety.
RESULTS
This study aims to establish the efficacy of durvalumab combined with carboplatin and paclitaxel in patients with extensive disease Small Cell Lung Cancer.
CLINICAL TRIAL REGISTRATION
EU CT: 2023-504670-38-00.
PubMed: 38843598
DOI: 10.1016/j.resmer.2024.101113 -
Frontiers in Neurology 2024Symptomatic intracranial in-stent restenosis (sISR) poses a major challenge in the management of cerebrovascular diseases, often requiring effective and safe treatment...
BACKGROUND
Symptomatic intracranial in-stent restenosis (sISR) poses a major challenge in the management of cerebrovascular diseases, often requiring effective and safe treatment options.
OBJECTIVES
This study aims to evaluate the efficacy and safety of paclitaxel-coated balloon (PCB) angioplasty for treating sISR.
METHODS
We conducted a retrospective analysis of five patients aged 49-74 years, who were treated with PCB angioplasty between January 2017 and June 2022. Treatment procedures included pre-operative digital subtraction angiography, antiplatelet therapy, and the use of the SeQuent Please balloon. Patients received aspirin and clopidogrel prior to and after the procedure.
RESULTS
The procedure achieved a 100% success rate. The degree of ISR was significantly reduced from an average pre-operative rate of 72±18.9% to a post-operative rate of 34±8.22%. Long-term follow-up showed that the majority of patients did not experience restenosis, confirming the long-term effectiveness of the treatment.
CONCLUSIONS
PCB angioplasty demonstrates significant potential as an effective and safe treatment option for patients with sISR, especially those considered to be at high risk. This study supports further investigation into PCB angioplasty as a standard treatment for sISR.
PubMed: 38841701
DOI: 10.3389/fneur.2024.1360609 -
Scientific Reports Jun 2024Alternaria alternata fungus is a potent paclitaxel producer isolated from Corylus avellana. The major challenge is the lack of optimized media for endophytic fungi...
Alternaria alternata fungus is a potent paclitaxel producer isolated from Corylus avellana. The major challenge is the lack of optimized media for endophytic fungi productivity. In the effort to maximize the production of taxoids by A. alternata, several fermentation conditions, including pH (pH 4.0-7.0), different types and concentrations of carbon (fructose, glucose, sucrose, mannitol, sorbitol, and malt extract), and nitrogen (urea, ammonium nitrate, potassium nitrate, ammonium phosphate, and ammonium sulfate) were applied step by step. Based on the results, A. alternata in a medium containing sucrose 5% (w/v) and ammonium phosphate 2.5 mM at pH 6.0 showed a rapid and sustainable growth rate, the highest paclitaxel yield (94.8 µg gFW vs 2.8 µg gFW in controls), and the maximum content of amino acids. Additionally, the effect of pectin was evaluated on fungus, and mycelia harvested. Pectin significantly enhanced the growth and taxoid yield on day 21 (respectively 171% and 116% of their corresponding on day 7). The results were checked out by mathematical modeling as well. Accordingly, these findings suggest a low-cost, eco-friendly, and easy-to-produce approach with excellent biotechnological potential for the industrial manufacture of taxoids.
Topics: Alternaria; Fermentation; Pectins; Culture Media; Paclitaxel; Models, Theoretical; Hydrogen-Ion Concentration; Nitrogen
PubMed: 38839906
DOI: 10.1038/s41598-024-63681-w -
Supportive Care in Cancer : Official... Jun 2024Alopecia is a common side-effect of chemotherapy and can be extremely distressing to patients. Scalp cooling can be used to reduce hair loss, but the optimal duration of... (Randomized Controlled Trial)
Randomized Controlled Trial
PURPOSE
Alopecia is a common side-effect of chemotherapy and can be extremely distressing to patients. Scalp cooling can be used to reduce hair loss, but the optimal duration of cooling remains unclear. Our aim was to determine whether increasing the duration of scalp cooling improves hair preservation.
METHODS
Patients with HER2-negative, non-metastatic, breast cancer received scalp cooling during adjuvant chemotherapy: three cycles of epirubicin/cyclophosphamide (EC) followed by three cycles of paclitaxel. The patients were randomly assigned to two groups. Group A (n=18) wore a Paxman cooling cap during each infusion and for 30 min post-infusion while Group B (n=19) wore the cap from 30 min before to 2 h after each infusion. All patients were asked to complete a questionnaire recording hair loss/regrowth, adverse events, and quality of life. Success of treatment was defined as <50% hair loss.
RESULTS
The success rates after each of the three cycles did not differ significantly between the two groups (EC: Group A: 40%, Group B: 44%; paclitaxel: Group A: 50%, Group B: 36%; p>0.05). Hair regrowth was significantly higher in Group B at the 8-week follow-up, but not at the 6-month follow-up. Head discomfort affected more patients in Group B than in Group A during the first session (94% vs. 62%, respectively; p=0.039).
CONCLUSION
Long duration scalp cooling during chemotherapy might increase patients' discomfort and does not appear to improve hair preservation.
Topics: Humans; Alopecia; Female; Breast Neoplasms; Pilot Projects; Middle Aged; Chemotherapy, Adjuvant; Antineoplastic Combined Chemotherapy Protocols; Cyclophosphamide; Paclitaxel; Adult; Scalp; Epirubicin; Quality of Life; Hypothermia, Induced; Time Factors; Aged; Surveys and Questionnaires
PubMed: 38839667
DOI: 10.1007/s00520-024-08579-z -
Cell Reports. Medicine Jun 2024Luminal androgen receptor (LAR)-enriched triple-negative breast cancer (TNBC) is a distinct subtype. The efficacy of AR inhibitors and the relevant biomarkers in...
Luminal androgen receptor (LAR)-enriched triple-negative breast cancer (TNBC) is a distinct subtype. The efficacy of AR inhibitors and the relevant biomarkers in neoadjuvant therapy (NAT) are yet to be determined. We tested the combination of the AR inhibitor enzalutamide (120 mg daily by mouth) and paclitaxel (80 mg/m weekly intravenously) (ZT) for 12 weeks as NAT for LAR-enriched TNBC. Eligibility criteria included a percentage of cells expressing nuclear AR by immunohistochemistry (iAR) of at least 10% and a reduction in sonographic volume of less than 70% after four cycles of doxorubicin and cyclophosphamide. Twenty-four patients were enrolled. Ten achieved a pathologic complete response or residual cancer burden-I. ZT was safe, with no unexpected side effects. An iAR of at least 70% had a positive predictive value of 0.92 and a negative predictive value of 0.97 in predicting LAR-enriched TNBC according to RNA-based assays. Our data support future trials of AR blockade in early-stage LAR-enriched TNBC.
Topics: Humans; Triple Negative Breast Neoplasms; Phenylthiohydantoin; Nitriles; Benzamides; Female; Receptors, Androgen; Middle Aged; Neoadjuvant Therapy; Paclitaxel; Aged; Adult; Antineoplastic Combined Chemotherapy Protocols
PubMed: 38838676
DOI: 10.1016/j.xcrm.2024.101595