A retrospective study of adjuvant albumin-bound paclitaxel plus S-1 after D2 gastrectomy versus oxaliplatin plus S-1 in gastric cancer.

Adjuvant oxaliplatin plus S-1 (SOX) chemotherapy for gastric cancer (GC) after D2 gastrectomy has been proven effective. There has yet to be a study that evaluates adjuvant nanoparticle albumin-bound paclitaxel (nab-paclitaxel) plus S-1. In this single-center, retrospective study, GC patients after D2 gastrectomy received either nab-paclitaxel plus S-1 (AS group) or SOX group were recruited between January 2018 and December 2020 in The First Affiliated Hospital of Zhejiang University. Intravenous nab-paclitaxel 120 mg/m2 or 260 mg/m2 and oxaliplatin 130 mg/m2 were administered as eight 3 week cycle, especially in the AS and SOX group. Patients received S-1 twice daily with a dose of 40 mg/m2 in the two groups on days 1-14 of each cycle. The end points were disease-free survival (DFS) rate at 3 years and adverse events (AEs). There were 56 eligible patients, 28 in the AS group and 35 in the SOX group. The 3 year DFS rate was 78.0% in AS group versus 70.7% in SOX group (p = 0.46). Subgroup analysis showed that the patients with signet-ring positive in the AS group had a prolonged DFS compared with the SOX group (40.0 vs. 13.8 m, p = 0.02). The diffuse-type GC or low differentiation in the AS group was associated with numerically prolonged DFS compared with the SOX group, but the association was not statistically significant (p = 0.27 and p = 0.15 especially). Leukopenia (14.3%) were the most prevalent AEs in the AS group, while thrombocytopenia (28.5%) in the SOX group. Neutropenia (7.1% in AS group) and thrombocytopenia (22.8% in SOX group) were the most common grade 3 or 4 AEs. In this study analyzing past data, a tendency towards a greater 3 year DFS was observed when using AS regimen in signet-ring positive patients. AS group had fewer thrombocytopenia compared to SOX group. More studies should be conducted with larger sample sizes.

Efficacy and safety of pyrotinib combined with albumin-bound paclitaxel as first-line treatment for HER2-positive metastatic breast cancer in patients previously treated with adjuvant and/or neoadjuvant trastuzumab therapy: The stage 1 results of a single-arm, phase 2 prospective clinical trial.

OBJECTIVE: It has been observed that the prognosis of patients with HER2-positive metastatic breast cancer has improved significantly with HER2-targeted agents. However, there is still a lack of evidence regarding first-line anti-HER2 treatment options for patients who have received adjuvant and/or neoadjuvant trastuzumab for HER2-positive metastatic breast cancer. Besides, there are no reliable markers that can predict the efficacy of anti-HER2 treatment in these patients. METHODS: Patients who have received adjuvant and/or neoadjuvant trastuzumab for HER2-positive metastatic breast cancer were enrolled. Pyrotinib plus albumin-bound paclitaxel were used as first-line treatment. The primary endpoint was the objective response rate (ORR). The safety profile was also assessed. In order to explore predictive biomarkers using Olink technology, blood samples were collected dynamically. RESULTS: From December 2019 to August 2023, the first stage of the study involved 27 eligible patients. It has not yet reached the median PFS despite the median follow-up being 17.8 months. Efficacy evaluation showed that the ORR was 92.6%, and the DCR was 100%. Adverse events of grade 3 or higher included diarrhoea (29.6%), leukopenia (11.1%), neutropenia (25.9%), oral mucositis (3.7%), and hand-foot syndrome (3.7%). Toll-like receptor 3 (TLR3) and Proto-oncogene tyrosine-protein kinase receptor (RET) were proteins with significant relevance to PFS in these patients. CONCLUSIONS: This study demonstrates that pyrotinib plus albumin-bound paclitaxel as a first-line treatment regimen shows good efficacy and manageable safety for patients who have received adjuvant and/or neoadjuvant trastuzumab for HER2-positive metastatic breast cancer. Besides, a significant association was identified between the expression levels of TLR3 and RET and the PFS in patients.

Evaluation of nanoparticle albumin-bound paclitaxel loaded macrophages for glioblastoma treatment based on a microfluidic chip.

Introduction: Glioblastoma (GBM) is a primary brain malignancy with a dismal prognosis and remains incurable at present. In this study, macrophages (MΦ) were developed to carry nanoparticle albumin-bound paclitaxel (nab-PTX) to form nab-PTX/MΦ. The aim of this study is to use a GBM-on-a-chip to evaluate the anti-GBM effects of nab-PTX/MΦ. Methods: In this study, we constructed nab-PTX/MΦ by incubating live MΦ with nab-PTX. We developed a microfluidic chip to co-culture GBM cells and human umbilical vein endothelial cells, mimicking the simplified blood-brain barrier and GBM. Using a syringe pump, we perform sustainable perfusion of nutrient media. To evaluate the anti-GBM effects nab-PTX/MΦ, we treated the GBM-on-a-chip model with nab-PTX/MΦ and investigated GBM cell proliferation, migration, and spheroid formation. Results: At the chosen concentration, nab-PTX did not significantly affect the viability, chemotaxis and migration of MΦ. The uptake of nab-PTX by MΦ occurred within 1 h of incubation and almost reached saturation at 6 h. Additionally, nab-PTX/MΦ exhibited the M1 phenotype, which inhibits tumor progression. Following phagocytosis, MΦ were able to release nab-PTX, and the release of nab-PTX by MΦ had nearly reached its limit at 48 h. Compared with control group and blank MΦ group, individual nab-PTX group and nab-PTX/MΦ group could inhibit tumor proliferation, invasion and spheroid formation. Meanwhile, the anti-GBM effect of nab-PTX/MΦ was more significant than nab-PTX. Discussion: Our findings demonstrate that nab-PTX/MΦ has a significant anti-GBM effect compared to individual nab-PTX or MΦ administration, suggesting MΦ as potential drug delivery vectors for GBM therapy. Furthermore, the developed GBM-on-a-chip model provides a potential ex vivo platform for innovative cell-based therapies and tailored therapeutic strategies for GBM.

Hemorrhagic cystitis in gastric cancer after nanoparticle albumin-bound paclitaxel: A case report.

BACKGROUND: The advanced first-line regimen for advanced gastric cancer is based on a combination of fluoropyrimidine and platinum and/or paclitaxel (PTX), forming a two- or three-drug regimen. Compared to conventional PTX, nanoparticle albumin-bound PTX (Nab-PTX) has better therapeutic effects and fewer adverse effects reported in studies. Nab-PTX is a great option for patients presenting with advanced gastric cancer. Herein, we highlight an adverse event (hemorrhagic cystitis) of Nab-PTX in advanced gastric cancer. CASE SUMMARY: A 55-year-old male was diagnosed with lymph node metastasis after a laparoscopic-assisted radical gastrectomy for gastric cancer that was treated by Nab-PTX and S-1 (AS). On the 15th day after treatment with AS, he was diagnosed with hemorrhagic cystitis. CONCLUSION: Physicians should be aware that hemorrhagic cystitis is a potential adverse event associated with Nab-PTX treatment.

Short-Term Safety Evaluation of Albumin-Bound Paclitaxel in Intraoperative and Postoperative Hyperthermic Intraperitoneal Chemotherapy for Gastric Cancer.

PURPOSE: To evaluate the short-term safety of albumin-bound paclitaxel in hyperthermic intraperitoneal chemotherapy (HIPEC) during and after gastric cancer (GC) surgery. METHODS: A retrospective analysis of clinical data was conducted for GC surgery patients at Zhongnan Hospital of Wuhan University, from January 2020 to September 2022. The study group (n = 120) received HIPEC and the control group (n = 268) did not receive albumin-bound paclitaxel. Short-term safety indicators including intraoperative complications, hematological toxicity, liver and kidney function, and gastrointestinal function recovery were compared between the two groups. RESULTS: There were no statistically significant differences between the two groups regarding intraoperative complications, hematological toxicity, liver and kidney function, and gastrointestinal function recovery time (P > 0.05 for all). In the study group, patients were further divided into subgroups based on dose and timing. Subgroup analysis revealed no significant differences among the different dose subgroups. However, when focusing on timing subgroups, the postoperative subgroup exhibited significantly higher white blood cell counts and bilirubin levels compared to the intraoperative subgroup, while the intraoperative subgroup had significantly higher bilirubin levels compared to both postoperative and intraoperative plus postoperative subgroups. CONCLUSION: Albumin-bound paclitaxel demonstrates good safety and tolerability in HIPEC during and after GC surgery, without increasing the risk of intraoperative complications.

Efficacy of Nanoparticle Albumin-Bound Paclitaxel (nab-PTX) Monotherapy Can Be Improved after Treatment with Immune Checkpoint Inhibitor in Patients with Non-Small Cell Lung Cancer: Long-Term Follow-Up and Updated Analysis of Two Previous Prospective Clinical Studies.

INTRODUCTION: Recent studies have suggested enhanced therapeutic effects of subsequent chemotherapy after immune checkpoint inhibitor (ICI) treatment, highlighting the importance of subsequent treatment selection. Nanoparticle albumin-bound paclitaxel (nab-PTX) is commonly used in subsequent chemotherapies; however, its efficacy as a subsequent treatment after ICI treatment has not been reported. METHODS: We retrospectively evaluated the efficacy and safety of nab-PTX using two prospective studies that we previously reported. The first study evaluated the efficacy and safety of nab-PTX as a second-line treatment after the failure of the first-line cytotoxic chemotherapy, excluding ICI (study 1; n = 32), and the other as a subsequent treatment after failure of ICI treatment, regardless of treatment line (study 2; n = 29). RESULTS: The objective response rate was significantly higher in study 2 {55.2% (95% confidence interval [CI]: 28.1-79.6)} than in study 1 (28.1% [95% CI: 13.7-46.7]) (p = 0.04). Although the disease control rate was slightly higher in study 2 (86.2% [95% CI: 65.9-97.0]) than in study 1 (71.9% [95% CI: 53.3-86.3]), there was no significant difference (p = 0.2). The median progression-free survival was significantly longer in study 2 than in study 1 (3.9 months [95% CI: 2.0-5.5] in study 1 vs. 5.6 months [95% CI: 3.0-12.8] in study 2; hazard ratio [HR]: 0.46 [95% CI: 0.27-0.81], p = 0.006). The median overall survival was slightly longer in study 2 despite the greater number of patients who received nab-PTX in late treatment line, but there was no significant difference between study 1 and study 2 (10.9 months [95% CI: 5.1-16.8] in study 1 vs. 11.9 months [95% CI: 7.6-24.8] in study 2; HR: 0.77 [95% CI: 0.46-1.31], p = 0.34). Safety profiles did not differ between the patients in studies 1 and 2. CONCLUSION: Nab-PTX monotherapy may be an effective subsequent treatment option after ICI treatment.

Prolonged progression-free survival achieved by gemcitabine, cisplatin, and albumin-bound paclitaxel for the treatment of advanced biliary tract cancers.

Background: A regimen of gemcitabine, cisplatin, and nab-paclitaxel (GPA) has shown promising results in patients with advanced biliary tract cancer (aBTC). Objectives: This study aimed to evaluate the benefit of GPA compared to a regimen of gemcitabine plus cisplatin (GP) in patients with aBTC. Design: Retrospective study. Methods: Patients with aBTC who received first-line chemotherapy with GPA or GP regimen at the Samsung Medical Center between July 2020 and June 2022 were included. The primary endpoint was progression-free survival (PFS). Results: In all, 37 patients were treated with GPA and 43 patients with GP. The GPA group showed significantly longer median PFS [12.0 months (95% CI, 7.2-16.8)] compared to the GP group [5.5 months (95% CI, 3.7-7.4; p = 0.007)]. The median overall survival (OS) was also longer in the GPA group [18.7 months (95% CI, 13.7-23.7)] than in the GP group [10.7 months (95% CI, 1.5-19.9); p = 0.021]. First-line chemotherapy with GPA was associated with longer PFS, while metastatic disease at initial diagnosis and post-treatment increase in CA 19-9 level were associated with worse PFS. Conclusion: The GPA regimen improved the PFS of patients with aBTC compared to the GP regimen but showed no significant benefit in terms of OS after adjusting for confounding variables. Further large-scale studies are required to establish optimal indications for GPA.

Comparing new and standard chemotherapy treatments for advanced biliary tract cancer: a study of effectiveness and survival In this study, researchers at Samsung Medical Center investigated the effectiveness of two chemotherapy regimens for advanced biliary tract cancer (aBTC) from July 2020 to June 2022. The study compared a new treatment combination, gemcitabine, cisplatin, and nab-paclitaxel (GPA), against the standard treatment of gemcitabine and cisplatin (GP). The main focus was on progression-free survival (PFS) ­ the time patients lived without their cancer worsening, and overall survival (OS) ­ the total lifespan after treatment. A total of 37 patients received the GPA treatment, while 43 received the GP treatment. The results showed that patients on the GPA regimen had a longer median PFS of 12.0 months, compared to 5.5 months for those on the GP regimen. This significant difference suggested that GPA might be more effective in slowing cancer progression. Moreover, the median OS was also longer for patients treated with GPA (18.7 months) than for those with the GP regimen (10.7 months). These findings indicated that GPA not only delayed the progression of cancer but also potentially increased the overall survival time of patients. However, when accounting for other factors that could influence the results, the advantage of GPA in terms of overall survival became less clear. This suggests that while GPA is effective in delaying disease progression, its impact on extending the overall life expectancy of patients with aBTC is not definitive. Despite these promising findings, the researchers cautioned that the benefits of the GPA regimen in extending overall survival need further investigation. The study underscores the potential of GPA in improving outcomes for aBTC patients but also highlights the necessity for more comprehensive studies. These future studies are needed to confirm the optimal treatment for this challenging cancer type. This research is a step towards better understanding and managing aBTC, a cancer that currently has limited treatment options.

Efficacy and safety of pembrolizumab combined with albumin-bound paclitaxel and nedaplatin for advanced esophageal squamous cell carcinoma.

Objective: This research aimed to assess the efficacy and safety of pembrolizumab (PBL) combined with albumin-bound paclitaxel (ab-Pac) and nedaplatin (NDP) for advanced esophageal squamous cell carcinoma (ESCC). Methods: A total of 47 ESCC patients were administered PBL or NDP on day 1 and ab-Pac on days 1 and 8, every 21 days for one cycle. Tumor and toxicities were evaluated every two cycles and every cycle, respectively. Results: The objective response rate was 68.1% and the disease control rate was 100%. The median follow-up was 16.7 months; median progression-free and overall survival were 12.6 and 19.9 months, respectively. Conclusion: The combination of PBL with ab-Pac and NDP proved to be an effective and safe treatment regimen for advanced ESCC.

Phase I dose-escalation study of nab-paclitaxel combined with cisplatin and capecitabin as induction chemotherapy followed by concurrent chemoradiotherapy in patients with nasopharyngeal carcinoma.

BACKGROUND AND PURPOSE: Nab-paclitaxel is a promising albumin-bound paclitaxel with a therapeutic index superior to that of docetaxel, but the optimal dose of nab-paclitaxel combined with cisplatin and capecitabine as induction chemotherapy followed by concurrent chemoradiotherapy for patients with locally advanced nasopharyngeal carcinoma remains unknown. MATERIALS AND METHODS: This was an open-label, single-arm study investigating the safety and efficacy of nab-paclitaxel + cisplatin + capecitabin as IC for three cycles, followed by cisplatin CCRT, conducted by using the standard "3 + 3" design in LA-NPC. If more than one-third of the patients in a cohort experienced dose-limiting toxicity (DLT), the dose used in the previous cohort was designated the maximum tolerated dose (MTD). The recommended phase 2 dose (RP2D) was defined as one level below the MTD. RESULTS: From 29 May 2021 to 17 March 2022, 19 patients with LA-NPC were enrolled, one patient withdrew informed consent. Two DLTs occurred in cohort 4 (grade 4 febrile neutropenia and grade 3 peripheral neuropathy), and an MTD was established as 225 mg/m2. The most frequent grade 3 or 4 adverse events were neutropenia (16.7 %), hypertriglyceridemia (16.7 %), leukopenia (5.6 %) and peripheral neuropathy (5.6 %) during IC. CONCLUSION: The RP2D is nab-paclitaxel 200 mg/m2 on day 1, combined with cisplatin 75 mg/mg2 on day 1 and capecitabin1000 mg/m2 on days 1-14, twice a day, every 3 weeks, for three cycles as an IC regimen prior to CCRT. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT04850235.

Efficacy and safety of camrelizumab combined with albumin-bound paclitaxel as third- or later-line regimen in patients with advanced non-small cell lung cancer.

Background: The clinical efficacy and safety of camrelizumab as a third- or later-line regimen in patients with advanced non-small cell lung cancer (NSCLC) have not been determined in large clinical trials. Objective: This study aimed to evaluate the clinical efficacy and safety of camrelizumab in combination with albumin-bound paclitaxel as a third- or later-line treatment for patients with advanced NSCLC. Methods: A total of 257 patients with advanced NSCLC who were histopathologically confirmed and failed in clinical second-line therapy regimens at Jiangxi Province Cancer hospital from January 2018 to December 2021 were retrospectively selected. Patients with advanced NSCLC were divided into the single treatment group (STG) of camrelizumab, and the combined treatment group (CTG) of camrelizumab in combination with albumin-bound paclitaxel according to the treatment regimen. The primary outcomes of interest were clinical efficacy[objective response rate (ORR) and disease control rate (DCR)], progression-free survival (PFS), and overall survival (OS). Survival data were analyzed using the Kaplan-Meier method, and the log-rank test was performed. Additionally, Cox proportional hazard regression was used to analyze the correlation of prognosis and baseline characteristics between subgroups, to identify the potential independent risk factors for PFS and OS. Furthermore, the occurrence of side effects was assessed according to the Common Terminology Criteria for Adverse Events (CTCAE 4.03). Results: Of the 257 patients with advanced NSCLC included in the research, 135 patients received camrelizumab, and 122 patients received camrelizumab plus albumin-bound paclitaxel. The ORR of CTG and STG was 59.84% and 50.38%, and the DCR was 77.05% and 65.93%, respectively. The median PFS in CTG was higher than that in the STG (5.27 vs. 3.57 months, P = 0.0074), and the median OS was longer (7.09 vs. 6.47 months, P < 0.01). The lines of treatment, metastases, and PD-L1 expression levels were independent risk factors for the mPFS and mOS of patients with advanced NSCLC. The occurrence of adverse events was similar between camrelizumab and camrelizumab plus albumin-bound paclitaxel groups. Conclusion: Camrelizumab combined with albumin-bound paclitaxel as the third- or later-line regimen greatly prolonged PFS and OS of advanced NSCLC patients. A prospective clinical trial is warranted.

Efficacy and safety of sintilimab plus albumin-bound-paclitaxel in recurrent or metastatic cervical cancer: a multicenter, open-label, single-arm, phase II trial.

Background: Sintilimab is an antibody against programmed cell death protein 1. We assessed the efficacy and safety of sintilimab plus albumin-bound (nab)-paclitaxel for the treatment of recurrent or metastatic cervical cancer. Methods: This multicenter, open-label, single-arm, phase II study (ClinicalTrials.gov identifier NCT04341883) enrolled patients with recurrent or metastatic cervical cancer who progressed after at least one line of systemic therapy. The patients received sintilimab 200 mg and nab-paclitaxel 260 mg/m2 body surface area every 3 weeks. The primary endpoint was objective response rate (ORR) assessed by investigators per Response Evaluation Criteria in Solid Tumors version 1.1. Key secondary endpoints were progression-free survival (PFS), overall survival (OS), duration of response (DoR), and safety. Findings: From January 13, 2020 to February 21, 2022, 27 patients were enrolled and received treatment. Median patient age was 50 years (range, 34-68 years). By data cut-off (May 22, 2022), in intention-to-treat population, ORR was 44.4% (95% CI, 24.4%-64.5%). The disease control rate was 88.9% (95% CI, 70.8%-97.6%). Median PFS was 5.2 months (95% CI, 2.7-7.7 months). Median DoR was 3.8 months (95% CI, 0.7-6.9 months), and median OS was 13.1 months (95% CI, 5.8-20.4 months). Treatment-related grade 3 or 4 adverse events (AEs) occurred in 44.4% of the patients, and the most common AEs were decreased neutrophil count (22.2%), decreased white blood cell count (14.8%), and anemia (7.4%). The most common potential immune-related AEs were grade 1-2 hypothyroidism (18.5%), neutropenia (11.1%), and rash (7.4%). Interpretation: Sintilimab plus nab-paclitaxel treatment shows promising antitumor activity and manageable toxicity in patients with advanced cervical cancer. Larger randomized controlled trials are required for validation. Funding: Innovent Biologics Co., Ltd.; Csps Holdings Co., Ltd.

Efficacy and safety of nanoparticle albumin-bound paclitaxel in advanced non-small cell lung cancer: A systematic review and meta-analysis of clinical trials and observational studies.

Background: The efficacy and safety of nanoparticle albumin-bound paclitaxel (nab-paclitaxel) in advanced non-small cell lung cancer (NSCLC) have yielded inconsistent findings. Materials and methods: We conducted a systematic review and meta-analysis, including comparative and noncomparative trials and cohort studies, to assess the efficacy and safety of nab-paclitaxel in advanced NSCLC. The search covered PubMed, CENTRAL, Scopus, and ClinicalTrials.gov until October 2022. Efficacy outcomes (OR, PR, progressive disease, OS, and PFS) and safety outcomes (neutropenia, leukopenia, thrombocytopenia, anemia, and sensory neuropathy) were analyzed. Results: Our meta-analysis included data from 35 studies (9 RCTs, 2 cohort studies, and 24 noncomparative studies). Nab-paclitaxel significantly improved OR rate (RRRCT 1.35 [95% CI 1.19, 1.53], I2 = 36.6%; RRcohort 1.67 [95% CI 1.30, 2.14], I2 = 4.3%) and PR rate (RRRCT 1.34 [95% CI 1.18, 1.53], I2 = 38.8%; RRcohort 1.59 [95% CI 1.22, 2.07], I2 = 19.4%) compared to the control group. It further demonstrated more pronounced benefits in squamous cell carcinoma and as a second-line treatment. Pooled evidence from the RCTs also indicated improved OS (HR 0.90 [95% CI 0.81, 0.99], I2 = 9.2%) and PFS (HR 0.84 [95% CI 0.76, 0.93], I2 = 14.5%) However, evidence on the reduction of adverse events with nab-paclitaxel treatment was insufficient, and biases in study selection and detection may have influenced the results. Conclusions: Nab-paclitaxel enhances OR, PR, PFS, and marginally improves OS in advanced NSCLC, particularly in patients with prior chemotherapy. Further research is needed to establish its safety advantages.

Corrigendum: Synergistic effects of nab-PTX and anti-PD-1 antibody combination against lung cancer by regulating Pi3K/AKT pathway through the Serpinc1 gene.

[This corrects the article DOI: 10.3389/fonc.2022.933646.].

Cystoid Macular Edema following Treatment with Nanoparticle Albumin-Bound Paclitaxel and Atezolizumab for Metastatic Breast Cancer.

Cystoid macular edema (CME) is a rare side effect associated with chemotherapy. Although the development of CME has been reported to occur following treatment with taxane drugs, such as nanoparticle albumin-bound paclitaxel (Nab-PTX), the occurrence of CME with treatment with atezolizumab has not yet been reported. Here, we report the case of a 49-year-old woman who developed CME 19 months into chemotherapy with Nab-PTX and atezolizumab. Improvement was not achieved with steroid injections into the Tenon's sac, and Nab-PTX and atezolizumab treatments were ceased. One month later, there was subjective improvement in her symptoms. Although many reports have indicated that cessation of chemotherapy has successfully improved CME, a specific treatment for CME has not yet been established. Clinicians should be aware of the ophthalmologic side effects and offer immediate treatment if symptoms develop.

Albumin-bound paclitaxel augment temozolomide treatment sensitivity of glioblastoma cells by disrupting DNA damage repair and promoting ferroptosis.

BACKGROUND: Temozolomide (TMZ) treatment efficacy in glioblastoma (GBM) patients has been limited by resistance in the clinic. Currently, there are no clinically proven therapeutic options available to restore TMZ treatment sensitivity. Here, we investigated the potential of albumin-bound paclitaxel (ABX), a novel microtubule targeting agent, in sensitizing GBM cells to TMZ and elucidated its underlying molecular mechanism. METHODS: A series of in vivo and in vitro experiments based on two GBM cell lines and two primary GBM cells were designed to evaluate the efficacy of ABX in sensitizing GBM cells to TMZ. Further proteomic analysis and validation experiments were performed to explore the underlying molecular mechanism. Finally, the efficacy and mechanism were validated in GBM patients derived organoids (PDOs) models. RESULTS: ABX exhibited a synergistic inhibitory effect on GBM cells when combined with TMZ in vitro. Combination treatment of TMZ and ABX was highly effective in suppressing GBM progression and significantly prolonged the survival oforthotopic xenograft nude mice, with negligible side effects. Further proteomic analysis and experimental validation demonstrated that the combined treatment of ABX and TMZ can induce sustained DNA damage by disrupting XPC and ERCC1 expression and nuclear localization. Additionally, the combination treatment can enhance ferroptosis through regulating HOXM1 and GPX4 expression. Preclinical drug-sensitivity testing based on GBM PDOs models confirmed that combination therapy was significantly more effective than conventional TMZ monotherapy. CONCLUSION: Our findings suggest that ABX has the potential to enhance TMZ treatment sensitivity in GBM, which provides a promising therapeutic strategy for GBM patients.

Clinical outcomes of immune checkpoint inhibitor plus nab-paclitaxel in metastatic upper tract urothelial carcinoma.

Background: Metastatic upper tract urothelial carcinoma (mUTUC) is a malignant cancer associated with poor prognosis. Few studies have investigated the clinical outcome of a recently developed combination regimen of programmed cell death 1 (PD-1) inhibitor plus nab-paclitaxel in mUTUC. Methods: We retrospectively retrieved data from the electronic medical records of cisplatin-ineligible or cisplatin-refractory mUTUC patients from five participating Chinese centers, who received treatment of PD-1 inhibitor plus nab-paclitaxel between April 2018 and January 2022. Clinical response was assessed according to Response Evaluation Criteria in Solid Tumors criteria version 1.1 (RECIST 1.1). Duration of response (DOR), overall survival (OS), and progression-free survival (PFS) were evaluated by the Kaplan-Meier method. Results: The confirmed overall response rate (ORR) was 14/34 (41.2%), and the disease control rate (DCR) was 24/34 (70.6%). Complete response (CR) was achieved in one case, partial response (PR) in 13 cases (38.2%), stable disease (SD) in 10 cases (29.4%), and progressive disease (PD) occurred in 10 cases (29.4%). After a median follow-up period of 16.0 months [95% confidence interval (CI): 9.9-22.1], 14 deaths were reported, with a median OS of 15.0 months (95% CI: 9.9-20.1); 22 progressions were reported, with a median PFS of 6.0 months (95% CI: 2.4-9.6). Patients with visceral metastasis had a similar PFS [hazard ratio (HR): 1.28, 95% CI: 0.53-3.09, P=0.574) and OS (HR: 1.94, 95% CI: 0.64-5.83, P=0.279] to patients with lymph node metastasis only. Conclusions: This real-world study suggests that PD-1 inhibitor plus nab-paclitaxel is effective in cisplatin-ineligible and cisplatin-refractory mUTUC patients with acceptable toxicity, especially for patients with visceral metastasis.

Biguanide-anchored albumin-based nanoplatform inhibits epithelial-mesenchymal transition and reduces the stemness phenotype for metastatic cancer therapy.

In clinical chemotherapy, albumin-bound paclitaxel (Abraxane) can improve the tumor targeting property and therapeutic efficacy of paclitaxel (PTX) against orthotopic malignancies. However, patients with metastatic cancer have a poor prognosis, probably due to the instability, chemoresistance, and inability of albumin-bound paclitaxel to alter the tumor microenvironment. Here we propose a new biguanide-modified albumin-based nanoplatform that encapsulates paclitaxel for the effective treatment of metastatic cancer. The PTX is encapsulated in poly (lactic-co-glycolic acid) cores coated with biguanide-modified albumin (HSA-NH). The functionalized nanoparticles (HSA-NH NPs) exhibit a remarkable stable profile with low drug release (P < 0.05 versus Abraxane), target tumor tissues, suppress epithelial-mesenchymal transition (EMT) events for anti-metastatic effects, and reduce the phenotype of cancer stem cells. As a result, HSA-NH NPs effectively prolong animal survival (55 days) by inhibiting not only primary tumor growth but also metastasis. This study provides proof of concept that the biguanide-anchored albumin-based nanoplatform encapsulating PTX is a powerful, safe, and clinically translational strategy for the treatment of metastatic cancer. STATEMENT OF SIGNIFICANCE: Albumin-bound paclitaxel (Abraxane) can increase paclitaxel's tumor targeting and therapeutic efficacy in clinical cancer treatments such as breast cancer. However, the instability, chemoresistance, and lack of tumor microenvironment modulation of albumin-bound paclitaxel may lead to poor therapeutic efficacy in metastatic cancer patients. Here we develop biguanide-anchored albumin-based nanoplatforms that encapsulate paclitaxel (HSA-NH NPs) for metastatic cancer treatment. Poly(lactic-co-glycolic acid) (PLGA) cores encapsulating paclitaxel improve the stability of HSA-NH NPs. Based on the activities of metformin, biguanide-anchored albumin adsorbed on PLGA cores improves paclitaxel efficacy, inhibits various aberrant changes during epithelial-mesenchymal transition, and reduces tumor cell stemness. The biguanide-anchored albumin-based nanoplatform encapsulating PTX can serve as a potent, safe, and clinically translational approach for metastatic cancer therapies.

Efficacy comparisons of solvent-based paclitaxel, liposomal paclitaxel, nanoparticle albumin-bound paclitaxel, and docetaxel after neoadjuvant systemic treatment in breast cancer.

PURPOSE: There are four kinds of taxanes: solvent-based paclitaxel (Sb-P), liposomal paclitaxel (Lps-P), nanoparticle albumin-bound paclitaxel (Nab-P), and docetaxel. This study aims to retrospectively evaluate the efficacy of different taxanes on neoadjuvant systemic treatment (NST) in breast cancer. METHODS: Patients who were diagnosed with breast cancer and had received integral NST from August 2013 to April 2022 were enrolled. The efficacy was divided into total pathological complete response (total-pCR), breast pathological complete response (breast-pCR), and axillary pathological complete response (axillary-pCR) for in-depth analysis and discussion. RESULTS: The choice of taxane was an independent risk factor for total-pCR and breast-pCR rates. The highest total-pCR and breast-pCR rates were found in the Nab-P group. The difference was not significant among all the taxanes in the axillary-pCR rate. CONCLUSION: Nab-P significantly improved the total-pCR and breast-pCR rates. It should be the first choice among taxanes in NST for breast cancer.

Sintilimab plus nab-paclitaxel as second-line treatment for advanced biliary tract cancer: study protocol for an investigator-initiated phase 2 trial (NapaSinti trial).

BACKGROUND: Biliary tract cancer (BTC) is a relatively rare but highly aggressive malignancy. However, there is currently no satisfactory second-line regimen for patients without specific genetic mutations. Nanoparticle albumin-bound paclitaxel, also known as nab-paclitaxel (Abraxane, Bristol Myers Squibb), has shown activity in patients with BTC. Studies investigating the immunogenic features of BTC suggested that checkpoint inhibition may lead to antitumor immune responses. In recent years, improved survival has been observed in patients treated with chemotherapy combined with immunotherapy across multiple cancer types, including BTC. This clinical trial aims to evaluate the efficacy and safety of second-line sintilimab in combination with nab-paclitaxel in advanced BTC patients. METHODS: The NapaSinti trial is a prospective, nonrandomized, open-label, phase 2 study conducted at a tertiary hospital in Chengdu, China. Eligible patients are those with histologically or cytologically confirmed locally advanced non-resectable or metastatic adenocarcinoma in the biliary tract (including intrahepatic cholangiocarcinoma, extrahepatic cholangiocarcinoma, and gallbladder cancer), aged between 18 and 75 years, with an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1, who have experienced disease progression after prior gemcitabine- or fluorouracil-based chemotherapy and have not received taxane or immune checkpoint inhibitor treatment. Enrolled patients will receive intravenous administration of sintilimab 200 mg on day 1 and nab-paclitaxel 125 mg/m2 on days 1 and 8, every three weeks. The primary endpoint is the objective response rate (ORR), while the secondary endpoints include overall survival (OS), progression-free survival (PFS), and safety. Exploratory objectives aim to identify biomarkers and molecular signatures for predicting response or prognosis. Using Simon's two-stage design, a total of 63 participants will be enrolled in the study. This trial was initiated in March 2022 in China. DISCUSSION: The NapaSinti trial evaluates the efficacy and safety of second-line sintilimab plus nab-paclitaxel for advanced biliary tract cancer. Additionally, the trial provides an opportunity for translational research. TRIAL REGISTRATION: Chinese Clinical Trial Registry ChiCTR2100052118. Registered October 19, 2021.

Safety signals of albumin-bound paclitaxel: Data mining of the Food and Drug Administration adverse event reporting system.

BACKGROUND: With the extensive application of paclitaxel for injection (albumin-bound), its adverse reactions have also received increasing attention. AIM: This study aims to provide a reference for the safe use of albumin-bound paclitaxel in clinical practice; adverse drug events signals of albumin-bound paclitaxel were reviewed and identified by data mining of the Food and Drug Administration (FDA) adverse event reporting system (FAERS). METHODS: The reporting odds ratio method was used for the quantitative detection of signals from the data in the FDA public data program (OpenFDA) during 2004-2019 for the albumin-bound paclitaxel. RESULTS: According to the OpenFDA, 1659 adverse events (AEs) were identified for albumin-bound paclitaxel. AEs were mostly observed in females rather than males, aged 45-64 years. AEs involved 17 system organ classes, mainly blood and lymphatic, gastrointestinal, hepatobiliary, respiratory, thoracic, and mediastinal systems, and general AEs. Safety signals were found in 20 unexpected adverse drug reactions which are not listed on drug labels, mainly including macular edema and lymphopenia. CONCLUSION: Identifying and evaluating albumin-bound paclitaxel-associated AEs signals by mining FAERS may help evaluate the safety profiles of albumin-bound paclitaxel and reduce the risk of medical treatment. In the clinical application of albumin-bound paclitaxel in addition to the adverse reactions mentioned in the drug instructions, lymphocyte changes should be paid close attention to, and eye monitoring should be conducted regularly to avoid drug withdrawal or organ damage caused by adverse reactions.