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Low-intensity pulsed ultrasound with concomitant administration of intravenous microbubbles (LIPU-MB) can be used to open the blood–brain barrier. We aimed to assess the safety and pharmacokinetics of LIPU-MB to enhance the delivery of albumin-bound paclitaxel to the peritumoural brain of patients with recurrent glioblastoma. We conducted a dose-escalation phase 1 clinical trial in adults (aged ≥18 years) with recurrent glioblastoma, a tumour diameter of 70 mm or smaller, and a Karnofsky performance status of at least 70. A nine-emitter ultrasound device was implanted into a skull window after tumour resection. LIPU-MB with intravenous albumin-bound paclitaxel infusion was done every 3 weeks for up to six cycles. Six dose levels of albumin-bound paclitaxel (40 mg/m2, 80 mg/m2, 135 mg/m2, 175 mg/m2, 215 mg/m2, and 260 mg/m2) were evaluated. The primary endpoint was dose-limiting toxicity occurring during the first cycle of sonication and albumin-bound paclitaxel chemotherapy. Safety was assessed in all treated patients. Analyses were done in the per-protocol population. Blood–brain barrier opening was investigated by MRI before and after sonication. We also did pharmacokinetic analyses of LIPU-MB in a subgroup of patients from the current study and a subgroup of patients who received carboplatin as part of a similar trial (NCT03744026). This study is registered with ClinicalTrials.gov, NCT04528680, and a phase 2 trial is currently open for accrual. 17 patients (nine men and eight women) were enrolled between Oct 29, 2020, and Feb 21, 2022. As of data cutoff on Sept 6, 2022, median follow-up was 11·89 months (IQR 11·12–12·78). One patient was treated per dose level of albumin-bound paclitaxel for levels 1 to 5 (40–215 mg/m2), and 12 patients were treated at dose level 6 (260 mg/m2). A total of 68 cycles of LIPU-MB-based blood–brain barrier opening were done (median 3 cycles per patient [range 2–6]). At a dose of 260 mg/m2, encephalopathy (grade 3) occurred in one (8%) of 12 patients during the first cycle (considered a dose-limiting toxicity), and in one other patient during the second cycle (grade 2). In both cases, the toxicity resolved and treatment continued at a lower dose of albumin-bound paclitaxel, with a dose of 175 mg/m2 in the case of the grade 3 encephalopathy, and to 215 mg/m2 in the case of the grade 2 encephalopathy. Grade 2 peripheral neuropathy was observed in one patient during the third cycle of 260 mg/m2 albumin-bound paclitaxel. No progressive neurological deficits attributed to LIPU-MB were observed. LIPU-MB-based blood–brain barrier opening was most commonly associated with immediate yet transient grade 1–2 headache (12 [71%] of 17 patients). The most common grade 3–4 treatment-emergent adverse events were neutropenia (eight [47%]), leukopenia (five [29%]), and hypertension (five [29%]). No treatment-related deaths occurred during the study. Imaging analysis showed blood–brain barrier opening in the brain regions targeted by LIPU-MB, which diminished over the first 1 h after sonication. Pharmacokinetic analyses showed that LIPU-MB led to increases in the mean brain parenchymal concentrations of albumin-bound paclitaxel (from 0·037 μM [95% CI 0·022–0·063] in non-sonicated brain to 0·139 μM [0·083–0·232] in sonicated brain [3·7-times increase], p<0·0001) and carboplatin (from 0·991 μM [0·562–1·747] in non-sonicated brain to 5·878 μM [3·462–9·980] μM in sonicated brain [5·9-times increase], p=0·0001). LIPU-MB using a skull-implantable ultrasound device transiently opens the blood–brain barrier allowing for safe, repeated penetration of cytotoxic drugs into the brain. This study has prompted a subsequent phase 2 study combining LIPU-MB with albumin-bound paclitaxel plus carboplatin (NCT04528680), which is ongoing. National Institutes of Health and National Cancer Institute, Moceri Family Foundation, and the Panattoni family. [Display omitted]

Purpose To investigate the efficacy of using surgical glove (SG) compression therapy to prevent nanoparticle albumin-bound paclitaxel (nab-PTX)-induced peripheral neuropathy. Patients and methods Patients with primary and recurrent breast cancer who received 260 mg/m 2 of nab-PTX were eligible for this case-control study. Patients wore two SGs of the same size, i.e., one size smaller than the size that fit their dominant hand, for only 90 min. They did not wear two SGs on the non-dominant hand, which served as the control hand. Peripheral neuropathy was evaluated at each treatment cycle using common terminology criteria for adverse events (CTCAE) version 4.0 and the Patient Neurotoxicity Questionnaire. The temperature of each fingertip of the compression SG-protected hand and control hand was measured using thermography. Results Between August 2013 and January 2016, 43 patients were enrolled and 42 were evaluated. The occurrence rates of CTCAE grade 2 or higher sensory and motor peripheral neuropathies were significantly lower for SG-protected hands than for control hands (sensory neuropathy 21.4 vs. 76.1 %; motor neuropathy 26.2 vs. 57.1 %). No patients withdrew from this study because they could not tolerate the compression from the SGs. SG compression therapy significantly decreased the temperature of each fingertip by 1.6–2.2 °C as compared with the temperature before chemotherapy ( p  < 0.0001). Conclusions SG compression therapy is effective for reducing nab-PTX-induced peripheral neuropathy. The nab-PTX exposure to the peripheral nerve may be decreased because the SG decreases microvascular flow to the fingertip.

Nanoparticle albumin-bound paclitaxel (Abraxane ® ) [hereafter referred to as nab -paclitaxel] is a taxane developed to avoid some of the toxicities associated with solvent-bound (sb) paclitaxel. Nab -paclitaxel, in combination with carboplatin, is indicated for the first-line treatment of non-small cell lung cancer (NSCLC) in patients who are not candidates for curative surgery and/or radiation therapy. This article summarizes pharmacological, efficacy and tolerability data relevant to the use of nab -paclitaxel in this indication. Compared with sb-paclitaxel plus carboplatin, nab -paclitaxel plus carboplatin significantly improved the objective response rate (ORR), but did not prolong progression-free survival or overall survival (OS), in the overall population of patients with advanced NSCLC in a multinational phase III trial. The nab -paclitaxel regimen also provided benefit over the sb-paclitaxel regimen in certain patient subgroups, including patients with squamous cell histology (in terms of ORR) and patients who were elderly (in terms of OS). Nab -paclitaxel plus carboplatin had a manageable tolerability profile with some benefits over sb-paclitaxel plus carboplatin, including lower rates of grade ≥3 neutropenia, peripheral neuropathy, arthralgia and myalgia, although was associated with more grade ≥3 anaemia and thrombocytopenia. Given its efficacy and tolerability, intravenous nab -paclitaxel plus carboplatin is a valuable first-line treatment option for patients with advanced NSCLC.

Albumin-bound paclitaxel (nab-paclitaxel) is a solvent-free formulation of paclitaxel that was initially developed more than a decade ago to overcome toxicities associated with the solvents used in the formulation of standard paclitaxel and to potentially improve efficacy. Nab-paclitaxel has demonstrated an advantage over solvent-based paclitaxel by being able to deliver a higher dose of paclitaxel to tumors and decrease the incidence of serious toxicities, including severe allergic reactions. To date, nab-paclitaxel has been indicated for the treatment of three solid tumors in the USA. It was first approved for the treatment of metastatic breast cancer in 2005, followed by locally advanced or metastatic non-small-cell lung cancer in 2012, and most recently for metastatic pancreatic cancer in 2013. Nab-paclitaxel is also under investigation for the treatment of a number of other solid tumors. This review highlights key clinical efficacy and safety outcomes of nab-paclitaxel in the solid tumors for which it is currently indicated, discusses ongoing trials that may provide new data for the expansion of nab-paclitaxel's indications into other solid tumors, and provides a clinical perspective on the use of nab-paclitaxel in practice.

Background This phase I/II study aimed to determine the maximum tolerated dose (MTD) of nanoparticle albumin-bound paclitaxel ( nab ® -paclitaxel) plus cisplatin as treatment for metastatic nasopharyngeal carcinoma (NPC). Methods Patients were enrolled into 1 of 3 dose cohorts, each with 21-day treatment cycles: 1) intravenous (IV) nab -paclitaxel 260 mg/m 2 on day 1; 2) IV nab -paclitaxel 140 mg/m 2 on days 1 and 8; 3) IV nab -paclitaxel 100 mg/m 2 on days 1, 8, and 15. All patients received IV cisplatin 75 mg/m 2 on day 1. Treatment continued for 4–6 cycles, or until progression or unacceptable toxicity. If more than one-third of the patients in a cohort experienced a dose-limiting toxicity (DLT), the dose used in the previous cohort would be designated the MTD. Secreted protein acidic and rich in cysteine (SPARC) expression was detected by immunohistochemistry staining. Results Sixty-nine patients were enrolled, of whom 64 and 67 were eligible for efficacy and safety analysis, respectively. Two DLTs occurred in cohort 1 (grade 4 febrile neutropenia, grade 3 myalgia), none occurred in cohort 2, and 2 occurred in cohort 3 (both grade 3 fatigue). The MTD was not reached. Partial responses were achieved by 42 patients, 15 had stable disease, and 7 had progressive disease, giving an overall response rate of 66 %. Median progression-free survival was 9 months (95 % CI, 6–12 months). Grade ≥ 3 adverse events were mainly hematologic. There was no significant difference between the 3 cohorts with respect to efficacy or safety. Biomarker analyses indicated that stromal, rather than tumoral, SPARC may predict the response to nab-paclitaxel in NPC. Conclusions Our findings suggest that nab -paclitaxel plus cisplatin is a highly active regimen with moderate toxicity for the treatment of metastatic NPC, which warrants further investigation in a phase III study. Trial registrations ClinicalTrials.gov ID: NCT01735409 . The trial was registered on November 20th, 2012.

Combination of the prodrug technique with an albumin nano drug-loaded system is a novel promising approach for cancer treatment. However, the long-lasting and far-reaching challenge for the treatment of cancers lies in how to construct the albumin nanometer drug delivery system with lead compounds and their derivatives. In this study, we reported the preparation of injectable albumin nanoparticles (NPs) with a high and quantitative drug loading system based on the Nab TM technology of paclitaxel palmitate (PTX-PA). Our experimental study on drug tissue distribution in vivo demonstrated that the paclitaxel palmitate albumin nanoparticles (Nab-PTX-PA) remained in the tumor for a longer time post-injection. Compared with saline and paclitaxel albumin nanoparticles (Abraxane ® ), intravenous injection of Nab-PTX-PA not only reduced the toxicity of the drug in normal organs, and increased the body weight of the animals but maintained sustained release of paclitaxel (PTX) in the tumor, thereby displaying an excellent antitumor activity. Blood routine analysis showed that Nab-PTX-PA had fewer adverse effects or less toxicity to the normal organs, and it inhibited tumor cell proliferation more effectively as compared with commercial paclitaxel albumin nanoparticles. This carrier strategy for small molecule drugs is based on naturally evolved interactions between long-chain fatty acids (LCFAs) and Human Serum Albumin (HSA), demonstrated here for PTX. Nab-PTX-PA shows higher antitumor efficacy in vivo in breast cancer models. On the whole, this novel injectable Nab-PTX-PA has great potential as an effective drug delivery system in the treatment of breast cancer.

The curative effects of nanoparticle albumin-bound (nab)-paclitaxel in the first-line treatment of metastatic breast cancer (MBC) are still controversial, with even more after the removal of marketing approval of indication of bevacizumab. Five electronic databases and the related resources were searched for eligible randomized clinical trials (RCTs) without year and language restrictions to perform a meta-analysis. The studies were comparing the efficacy and safety between nab-paclitaxel chemotherapy versus solvent-based (sb)-taxanes chemotherapy such as sb-paclitaxel and docetaxel. The primary end points were overall response rate (ORR) and disease control rate (DCR). Secondary end points were progression-free survival (PFS), overall survival (OS), adverse events (AEs), and dose discontinuation rate (DDR). Five RCTs (1,554 patients) were finally identified from 1,902 studies. When compared to sb-paclitaxel, nab-paclitaxel showed significant beneficial effects in terms of ORR (OR 2.39, 95% CI 1.69–3.37, p < 0.001), DCR (OR 1.89, 95% CI 1.07–3.35, p = 0.03), and PFS (HR 0.75, 95% CI 0.62–0.90, p = 0.002). Nab-paclitaxel also showed significantly longer OS (HR 0.73, 95% CI 0.54–0.99, p = 0.04) than docetaxel. AEs and DDR were comparable between the two arms. Using nab-paclitaxel could significantly improve efficacy with comparable toxicities in the treatment of MBC.

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.

Current first-line treatment options for human epidermal growth factor receptor 2 (HER2)-negative advanced gastric or gastroesophageal junction (G/GEJ) adenocarcinoma have limited efficacy. This study aimed to evaluate the efficacy and safety of camrelizumab plus albumin-bound paclitaxel and S-1 as first-line treatment for this population. In this phase 2 trial (NCT04675866), patients received albumin-bound paclitaxel (125 mg/m , days 1 and 8) and S-1 (40-60 mg per body surface area, twice daily on days 1-14) for 4-6 cycles of 21 days each. Camrelizumab (200 mg every 3 weeks) was concurrently initiated and continuously administered until disease progression, intolerable toxicity, or completion of 2-year treatment. The primary endpoint was objective response rate (ORR). Between December 2020 and December 2024, 47 patients were enrolled. By the data cutoff date (January 6, 2025), the median follow-up duration was 16.7 months (range, 1.6-42.2 months). Among the 40 patients with evaluable efficacy, the ORR was 67.5% (95% CI: 52.3%-82.7%). The disease control rate was 95.0%. Median progression-free survival was 7.8 (95% CI: 6.2-9.4) months, and median overall survival was 23.8 (95% CI: 15.2-32.4) months. Grade 3-4 treatment-related adverse events(TRAEs) occurred in 18 patients (38.3%), with the most common being decreased neutrophil count (12 [25.5%]) and anemia (four [8.5%]). The combination of camrelizumab, albumin-bound paclitaxel, and S-1 as first-line treatment for patients with HER2-negative advanced G/GEJ adenocarcinoma showed promising efficacy and an acceptable safety profile. Randomized controlled clinical trials are required to further demonstrate its efficacy and optimal application scenario. https://clinicaltrials.gov/study/NCT04675866?term=Hou%20Xinfang&rank=1, identifier NCT04675866.

The present study is the first phase II clinical trial aimed to evaluate the efficacy and safety of S‐1 plus nanoparticle albumin‐bound paclitaxel (Nab‐PTX) as first‐line chemotherapy for advanced gastric cancer (AGC). Previously untreated patients with metastatic gastric adenocarcinoma received S‐1 in oral doses of 40 mg (BSA <1.25 m2), 50 mg (1.25 ≤ BSA < 1.50 m2) and 60 mg (BSA ≥1.50 m2) b.i.d. on days 1‐14 in combination with Nab‐PTX (120 mg/m2, on days 1 and 8) for each 21‐day cycle. Primary endpoint was progression‐free survival (PFS), and secondary endpoints were overall response rate (ORR), overall survival (OS), disease control rate (DCR), and toxicity. A total of 73 gastric cancer patients with metastatic and measurable lesions were enrolled in the first‐line setting. Median PFS and OS were 9.63 months and 14.60 months, respectively. Four (5.5%) patients had complete responses, 39 (53.4%) had partial responses (PRs), 21 (28.8%) had stable disease, four (5.5%) progressed and five (6.8%) were not evaluable. ORR and DCR were 58.9% and 87.7%, respectively. Most toxicities were mild, and no treatment‐related deaths occurred. Grade 3 to 4 toxicities occurred in 22 patients (30.1%) as follows: leukopenia (13.7%), neutropenia (12.3%), anemia (5.5%), thrombocytopenia (1.4%), diarrhea (6.8%), vomiting (2.7%), stomatitis (1.4%), peripheral neuropathy (1.4%), and hand‐foot syndrome (1.4%). Seven patients achieved good responses and underwent gastrectomy plus metastasectomy. Thirty (41.1%) patients had S‐1 maintenance with a median of four cycles. S‐1 plus Nab‐PTX is an efficient and safe regimen as first‐line treatment for patients with AGC. As the first phase II study of fluoropyrimidines plus nanoparticle albumin‐bound paclitaxel (Nab‐PTX) in gastric cancer patients, this study found that S‐1 plus Nab‐PTX is an efficient and safe regimen as first‐line treatment for patients with advanced gastric cancer.