We investigated the efficacy and toxicity of thoracic radiation therapy (RT) plus concurrent and consolidation carboplatin with either solvent-based paclitaxel (sb-paclitaxel) or solvent-free nanoparticle albumin-bound paclitaxel (nab-paclitaxel).

This multicenter phase 1/2 randomized trial included patients with inoperable stage IIIA/B nonsmall cell lung cancer (AJCC 7) and an Eastern Cooperative Oncology Group performance status of 0-1. In phase 1, 6 patients received weekly nab-paclitaxel (50 mg/m²) and carboplatin (AUC 2) with concurrent thoracic RT (60 Gy in 30 fractions), followed by nab-paclitaxel (100 mg/m²) on days 1, 8, and 15 and carboplatin (AUC 6) on day 1 for two 21-day cycles. In phase 2, 92 patients were randomly assigned to weekly sb-paclitaxel (50 mg/m²) or nab-paclitaxel (40 mg/m²) with concurrent RT, followed by consolidation therapy with sb-paclitaxel or nab-paclitaxel and carboplatin for 2 cycles.

Two phase 1 patients had dose-limiting toxicities, setting the phase 2 nab-paclitaxel dose at 40 mg/m². For the phase 2 cohort, 2-year overall survival was 67% for sb-paclitaxel and 56% for nab-paclitaxel (P = .10), with progression-free survival of 44% and 27%, respectively (P = .14). Fewer patients completed consolidation with nab-paclitaxel (26%) versus sb-paclitaxel (58%) (P = .005). Grade 3 and higher adverse events were more frequent with nab-paclitaxel (56%) than with sb-paclitaxel (30%) (P = .029).

Nab-paclitaxel was associated with higher toxicity and numerically lower efficacy than sb-paclitaxel when used with thoracic radiation in locally advanced nonsmall cell lung cancer.

Non-small cell lung cancer (NSCLC), as the most commonly diagnosed type of lung cancer, has long been a major focus for cancer drug researchers. Traditional chemotherapy has shown significant efficacy in patients initially diagnosed with NSCLC; however, with the emergence of drug resistance and notable toxic side effects, conventional and single-agent chemotherapy can no longer meet the treatment needs of patients. Nanomedicine systems have gained widespread attention among scholars due to their unique advantages, such as particle size, stable in vivo circulation, and multifunctional carrier materials. However, most single-drug delivery systems fail to meet the treatment expectations for NSCLC patients, prompting the active development of co-delivery nanomedicine systems in preclinical NSCLC research. These systems can utilize surface-modified carriers to co-deliver drugs, genes, photosensitizers, or sonosensitizers with different mechanisms of action. This approach not only achieves the synergistic effects of multiple drugs, multiple pathways, and the combination of chemotherapy with photodynamic/sonodynamic therapy but also, through the encapsulation of inorganic materials, allows for more controllable drug release under external forces such as magnetic fields. This further amplifies the synergistic effects between the drugs, and the results of these studies are significantly superior to those of single-drug treatments. In conclusion, this review summarizes the delivery strategies and the extended use of inorganic materials in the co-delivery of nanoparticles for NSCLC research in recent years, with the hope of providing reference for researchers' drug design strategies.

Nanotechnology has revolutionized cancer therapy by introducing advanced drug delivery systems that enhance therapeutic efficacy while reducing adverse effects. By leveraging various nanoparticle platforms-including liposomes, polymeric nanoparticles, and inorganic nanoparticles-researchers have improved drug solubility, stability, and bioavailability. Additionally, new nanodevices are being engineered to respond to specific physiological conditions like temperature and pH variations, enabling controlled drug release and optimizing therapeutic outcomes. Beyond drug delivery, nanotechnology plays a crucial role in the theranostic field due to the functionalization of specific materials that combine tumor detection and targeted treatment features. This review analyzes the clinical impact of nanotechnology, spanning from early-phase trials to pivotal phase 3 studies that have obtained regulatory approval, while also offering a critical perspective on the preclinical domain and its translational potential for future human applications. Despite significant progress, greater attention must be placed on key challenges, such as biocompatibility barriers and the lack of regulatory standardization, to ensure the successful translation of nanomedicine into routine clinical practice.

Lung cancer is one of the most prevalent tumor diagnoses and a leading cause of cancer-related mortality worldwide. Among its two primary subtypes, non-small cell lung cancer (NSCLC) accounts for approximately 80-85% of all lung cancer cases. Over the past decade, a significant number of publications have explored the application of nanomaterials in NSCLC. This study aimed to comprehensively evaluate the current state and evolving trends in research focused on utilizing nanomaterials as potent diagnostic and therapeutic tools for NSCLC.

To identify all pertinent publications, we used the Web of Science Core Collection (WoSCC) database. Based on stringent inclusion and exclusion criteria, relevant publications were carefully selected. For the bibliometric and visual analyses, we employed VOSviewer (version 1.6.20), CiteSpace (version 6.1.6), and R-bibliometrix (version 4.3.2).

Our analysis encompassed 1880 studies that fulfilled the inclusion criteria. We observed a steady increase in annual publications from 2014 to June 22, 2024. China, the USA, and India have emerged as leading nations in this field. Notably, the Chinese Academy of Sciences and Wang J stood out as the most influential institutions and authors, respectively. Most publications are featured in The International Journal of Nanomedicine. The keywords used in these publications were closely tied to non-small cell lung cancer and nanomaterials. In the past three years, "green synthesis" exhibited the highest burst strength, while "immune response" and "nanocrystal" represented emerging areas of intense research interest.

Through our exhaustive analysis, we synthesized the current research trends and emerging landscapes of nanomaterials in NSCLC. We characterized the publication patterns, pinpointed the most influential nations, institutions, authors, journals, and hot topics related to nanomaterial applications in NSCLC, and proposed potential avenues for future development.

Non-small cell lung cancer (NSCLC) is frequently diagnosed at an advanced stage, with 20 % of cases presenting as localized disease, 25 % with regional metastasis, and 55 % with distant metastasis, contributing significantly to increased morbidity and mortality rates. Current treatments, including chemotherapy, immunotherapy, radiotherapy and targeted therapy, have shown therapeutic efficacy but are limited by issues such as lack of specificity, cytotoxicity, and therapeutic resistance. Nanoparticles (NPs) offer promising solutions to these challenges by enhancing drug penetration and retention, improving biocompatibility and stability, and achieving greater precision in targeting cancer cells. This review provides insights into various types of NPs utilized in anti-metastatic drug delivery, emphasizing their ability to enhance the efficacy of existing chemotherapeutics for the prophylaxis of metastatic NSCLC. The usage of NPs as carriers of synthetic and natural compounds aimed at inhibiting cancer cell migration and invasion have also been reviewed. Special attention has been given to biomimetic nanomaterials including extracellular vesicles and engineered exosomes, that are capable of targeting molecular pathways such as EMT, p53 and PI3K/Akt to treat metastatic NSCLC. Additionally, emphasis has been given to clinical trials of these nanoformulations and their efficacy. Although therapeutic outcomes have demonstrated certain improvements, challenges related to toxicity persist, highlighting the need for further optimization of these formulations to enhance safety and efficacy. Finally, we discuss the current limitations and future perspectives for integrating NPs into clinical settings as novel therapeutic agents for lung cancer metastasis.

Syndrome of inappropriate antidiuretic hormone secretion (SIADH) is the most common cause of hyponatremia. Although SIADH induced by carboplatin (CBDCA) plus nab-paclitaxel (nab-PTX) has been reported, there is limited evidence for SIADH being suspected by pharmacists during chemotherapy in elderly patients and contributing to early intervention through diagnostic support for physicians.

An 84-year-old man was diagnosed with stage 3A squamous cell carcinoma of the right lung. Genetic mutations and expression of programmed cell death protein ligand 1 were < 1%. The patient was started on CBDCA area under the curve of 5 mg/mL·min on day 1 plus nab-PTX 70 mg/m2 on days 1, 8 and 15 once every 3 weeks. The serum sodium level immediately before the start of chemotherapy was 141 mmol/L. On day 8, it decreased to 119 mmol/L, and the physician started oral sodium chloride (3 g/day) administration. Because the pharmacist suspected that this hyponatremia may be due to chemotherapy-induced SIADH, the pharmacist suggested an examination of plasma and urine osmolality and urinary sodium levels to the physician. The serum creatinine level, plasma osmolality, urine osmolality, and urinary sodium level were 1.06 mg/dL, 253 mOsm/kg, 355 mOsm/kg, and 59 mEq/L, respectively; furthermore, the patient was not dehydrated. Based on the findings, a diagnosis of chemotherapy-induced SIADH was made. The physician and pharmacist conferred and decided to continue chemotherapy with frequent monitoring of serum sodium levels. Subsequently, the serum sodium level improved to 139 mmol/L on day 20 without additional treatment, and oral administration of sodium chloride was discontinued on day 22. The patient completed five cycles of chemotherapy. Computed tomography revealed a partial response throughout chemotherapy. Furthermore, sodium levels did not decrease again throughout chemotherapy. The Naranjo Adverse Drug Reaction Probability Scale score was 5 points, which is categorized as "probable."

We encountered a case in which the patient developed chemotherapy-induced SIADH but was able to continue chemotherapy because of early pharmacist intervention. In elderly patients without genetic mutations and few treatment options, even if they develop SIADH, chemotherapy should be continued with monitoring of serum sodium levels by physicians and pharmacists.

Triple-negative breast cancer (TNBC) is a highly aggressive form of breast cancer. Common treatments following surgical resection include PD-1-targeting checkpoint inhibitors (pembrolizumab), as 20% of tumors are PD-L1 positive with or without systemic chemotherapy. Over the last several years, our laboratory has developed nano-immune conjugates (NIC) in which hydrophobic chemotherapy drugs like paclitaxel (PTX) and SN38, the active metabolite of irinotecan, are made water soluble by formulating them into albumin-based nanoparticles (nab) that are hydrophobically linked to various IgG1 monoclonal antibodies, creating an antigen-targetable nano-immune conjugate. To date, we have successfully tested PTX containing NICs linked to either VEGF- or CD20-targeted antibodies in two phase I clinical trials against multiple relapsed ovarian/uterine cancer or non-Hodgkin's lymphoma, respectively. Herein, we describe a novel NIC created with either PTX or SN38 that is coated with anti-PD-L1-targeting antibodies for the treatment of a preclinical model of TNBC. In vitro testing suggests that the chemotherapy drug and antibody retain their toxicity and ligand binding capability in the context of the NIC. Furthermore, both the PTX and SN-38 NIC demonstrate superior anti-tumor efficacy relative to antibody and chemotherapy drugs alone in a PD-L1 + MDA-MB-231 human TNBC xenograft model, which could translate clinically to patients with TNBC.

Precision dosing of classical cytotoxic drugs in oncology remains underdeveloped, especially in treating non-small cell lung cancer (NSCLC). Despite advancements in targeted therapy and immunotherapy, classical cytotoxic agents continue to play a critical role in NSCLC treatment. However, the current body surface area (BSA)-based dosing of these agents fails to adequately address interindividual variability in pharmacokinetics. By better considering patient characteristics, treatment outcomes can be improved, reducing risks of under-exposure and over-exposure. This narrative review explores opportunities for precision dosing for key cytotoxic agents used in NSCLC treatment: cisplatin, carboplatin, pemetrexed, docetaxel, (nab-)paclitaxel, gemcitabine, and vinorelbine. A comprehensive review of regulatory reports and an extensive literature search were conducted to evaluate current dosing practices, pharmacokinetics, pharmacodynamics, and exposure-response relationships. Our findings highlight promising developments in precision dosing, although the number of directly implementable strategies remains limited. The most compelling evidence supports using the biomarker cystatin C for more precise carboplatin dosing and adopting weekly dosing schedules for docetaxel, paclitaxel, and nab-paclitaxel. Additionally, we recommend direct implementation of therapeutic drug monitoring (TDM)-guided dosing for paclitaxel. This review stresses the urgent need to reassess conventional dosing paradigms for classical cytotoxic agents to better align with the principles of the precision dosing framework. Our recommendations show the potential of precision dosing to improve NSCLC treatment, addressing gaps in the current dosing of classical cytotoxic drugs. Given the large NSCLC patient population, optimising the dosing of these agents could significantly improve treatment outcomes and reduce toxicity for many patients.

Albumin-bound paclitaxel (nab-PTX) is an important chemotherapeutic drug used for the treatment of advanced and metastatic non-small cell lung cancer (NSCLC). One critical issue in its clinical application is the development of resistance; thus, a deeper understanding of the mechanisms underlying the primary resistance to nab-PTX is expected to help to develop effective therapeutic strategies to overcome resistance. In this study, we made an unexpected discovery that NSCLC with wild-type (WT) Liver kinase B1 (LKB1), an important tumor suppressor and upstream kinase of AMP-activated protein kinase (AMPK), is more resistant to nab-PTX than NSCLC with mutant LKB1. Mechanistically, LKB1 status does not alter the intracellular concentration of nab-PTX or affect its canonical pharmacological action in promoting microtubule polymerization. Instead, we found that LKB1 mediates AMPK activation, leading to increased expression of SLC7A11, a key amino acid transporter and intracellular level of glutathione (GSH), which then attenuates the production of reactive oxygen species (ROS) and apoptotic cell death induced by nab-PTX. On the other hand, genetic or pharmacological inhibition of AMPK in LKB1-WT NSCLC reduces the expression of SLC7A11 and intracellular GSH, increases ROS level, and eventually promotes the apoptotic cell death induced by nab-PTX in vitro. Consistently, the combination of nab-PTX with an AMPK inhibitor exhibits a greater therapeutic efficacy in LKB1-WT NSCLC using xenograft models in vivo. Taken together, our data reveal a novel role of LKB1-AMPK-SLC7A11-GSH signaling pathway in the primary resistance to nab-PTX, and provide a therapeutic strategy for the treatment of LKB1-WT NSCLC by targeting the LKB1-AMPK-SLC7A11-GSH pathway.

High-grade chemotherapy-induced peripheral neuropathy (CIPN) represents a dreaded toxicity of cancer treatments. In some cases, it may limit activities of daily living and become permanent. Because many prior studies of CIPN were conducted in breast cancer populations, less is known about CIPN in men. We therefore determined the incidence and correlates of high-grade CIPN in a large cohort of patients with lung cancer.

We collected data from the ECOG-ACRIN E1594 (comparison of 4 chemotherapy regimens: cisplatin-paclitaxel, cisplatin-gemcitabine, cisplatin-docetaxel, carboplatin-paclitaxel) and E4599 (carboplatin-paclitaxel ± concurrent and maintenance bevacizumab) clinical trials. We identified cases with grade ≥3 CIPN. Multivariable logistic regression modeling was performed to estimate adjusted odds ratios according to patient characteristics.

Among 1,998 patients included in the study, 167 (8%) developed grade ≥3 CIPN. Grade ≥3 CIPN was associated with higher body mass index (BMI) (P = .01), sex (7% for men vs 10% for women; P = .005), age (11% for ≥65 years vs 7% for <65 years; P < .001), chemotherapy regimen (P = .01), and greater number treatment cycles (P < .001). In a multivariate model, regimens featuring higher doses of paclitaxel or cisplatin, greater number of chemotherapy cycles, female sex, greater age, and higher BMI remained independently associated with grade ≥3 CIPN.

High-grade CIPN is associated with chemotherapy type and exposure, female sex, greater age, and elevated BMI. Given the ongoing use of cytotoxic agents in established and new (eg, antibody-drug conjugates) treatment regimens, these findings have implications for patient monitoring and treatment selection.

Lung cancer remains the most common malignancy independent of sex. Here, we focused on unraveling the molecular mechanisms of CaS nanoclusters inducing cytotoxicity by investigating DNA damage, the cell cycle, oxidative stress, and cellular repair mechanisms in non-small-cell lung carcinoma (NSCLC) cells compared to healthy lung fibroblasts. Our previous studies have demonstrated the therapeutic potential of calcium sulfide (CaS) nanostructures in skin and breast cancer models, leading to a significant reduction in cancer cell proliferation. However, how CaS nanoclusters enhance their therapeutic effects on cancer cells while minimizing damage to healthy cells remains unknown. Our results show that CaS nanoclusters, once dissociated into Ca2+ and H2S in an acidic microenvironment, selectively allow extracellular calcium to enter, leading to an increase in free calcium entry, triggering oxidative stress and limiting DNA repair mechanisms in NSCLC. Furthermore, CaS nanoclusters selectively arrest NSCLC cells in the G0-G1 and S phases of the cell cycle without affecting healthy cells' cycles. Here, we also show that the selective effects of CaS nanoclusters on lung adenocarcinoma are less likely to be regulated by intrinsic apoptotic or mitochondrial pathways. They are, rather, caused by an increase in Ca2+ and ROS, causing double-stranded DNA breakages. This selectivity for malignant cells is pH-dependent because it occurs in the acidic microenvironment characteristic of these cells. Overall, this is the first piece of evidence that CaS disrupts genomic stability, prevents the replication of damaged cells, and ultimately influences cell fate decisions such as cell cycle arrest or cell death including mitotic catastrophe and necroptotic simultaneous events.

The size of nanodrugs plays a crucial role in shaping their chemical and physical characteristics, consequently influencing their therapeutic and diagnostic interactions within biological systems. The optimal size of nanomedicines, whether small or large, offers distinct advantages in disease treatment, creating a dilemma in the selection process. Addressing this challenge, size-transformable nanodrugs have surfaced as a promising solution, as they can be tailored to entail the benefits associated with both small and large nanoparticles. In this review, various strategies are summarized for constructing size-transformable nanosystems with a focus on nanotherapeutic applications in the field of biomedicine. Particularly we highlight recent research developments in cancer therapy. This review aims to inspire researchers to further develop various toolboxes for fabricating size-transformable nanomedicines for improved intervention against diverse human diseases.

Although immunotherapy combinations have revolutionised cancer treatment, the rapid screening of effective and optimal therapies from large numbers of candidate combinations, as well as exploring subgroup efficacy, remains challenging. This necessitates innovative, integrated, and efficient trial designs. In this study, we extend the MIDAS design to include subgroup exploration and propose an enhanced Bayesian information borrowing platform design called MIDAS-2. MIDAS-2 enables quick and continuous screening of promising combination strategies and exploration of their subgroup effects within a unified platform design framework. We use a regression model to characterize the efficacy pattern in subgroups. Information borrowing is applied through Bayesian hierarchical modelling to improve trial efficiency considering the limited sample size in subgroups. Time trend calibration is also employed to avoid potential baseline drifts. Simulation results demonstrate that MIDAS-2 yields high probabilities for identifying the effective drug combinations as well as promising subgroups, facilitating appropriate selection of the best treatments for each subgroup. The proposed design is robust against small time trend drifts, and the type I error is successfully controlled after calibration when a large drift is expected. Overall, MIDAS-2 provides an adaptive drug screening and subgroup exploring framework to accelerate immunotherapy development in an efficient, accurate, and integrated fashion.

The simultaneous occurrence of head and neck squamous carcinoma in two anatomical sites is rare, posing challenges in treatment selection. This paper presents a clinical case of concurrent hypopharyngeal carcinoma and nasopharyngeal carcinoma, successfully treated with a combination of chemoradiotherapy and an immune checkpoint inhibitor. The patient achieved complete remission and progression-free survival of nearly 3 years, with preserved organ function and minimal toxic side effects, leading to a good quality of life. This case highlights the potential of combined concurrent chemoradiotherapy and immune checkpoint inhibitors in managing double primary HNSCC, offering a promising treatment option for these patients.

Recent developments in nanotechnology have regained hope in enabling the eradication of lung cancer, while overcoming the drawbacks of the classic therapeutics. Nevertheless, there are still formidable obstacles that hinder the translation of such platforms from the bench into the clinic. Herein, we shed light on the clinical potential of these formulations and discuss their future directions.

The current article sheds light on the recent advancements in the recruitment of nanoformulations against lung cancer, focusing on their unique features, merits, and demerits. Moreover, inorganic nanoparticles, including gold, silver, magnetic, and carbon nanotubes are highlighted as emerging drug delivery technologies. Furthermore, the clinical status of these formulations is discussed, with particular attention on the challenges that they encounter in their clinical translation. Lastly, the future perspectives in this promising area are inspired.

Nanoformulations have a promising potential in improving the physico-chemical properties, pharmacokinetics, delivery efficiency, and selectivity of lung cancer therapeutics. The key challenges that encounter their clinical translation include their structural intricacy, high production cost, scale-up issues, and unclear toxicity profiles. The application of biodegradable platforms improves the biosafety of lung cancer-targeted nanomedicine. Moreover, the design of novel targeting strategies that apply a lower number of components can promote their industrial scalability and deliver them to the market at affordable prices.

Nanomedicines have opened up new possibilities for treating lung cancer. Focusing on tackling the challenges that hinder their clinical translation will promote the future of this area of endeavor.

Doublet platinum or taxane-based therapies are the current standard backbone of treatment for advanced gastric/gastroesophageal junction (GEJ) adenocarcinoma. Previously used anthracycline-based triplet regimens are no longer used routinely due to toxicity and lack of superior efficacy. We hypothesized that the addition of nab-paclitaxel to FOLFOX (FOLFOX-A) would induce higher efficacy and better tolerability.

Eligible patients with chemotherapy-naïve advanced unresectable HER2-negative gastric or GEJ adenocarcinoma were enrolled in this phase II single-arm trial of FOLFOX (oxaliplatin 85 mg/m2, leucovorin 400 mg/m2, 5-FU 2400 mg/m2 over 46-48 hours) + nab-paclitaxel (150 mg/m2) every 14 days of a 28-day cycle. Evaluable disease according to RECIST v1.1 for solid tumors was required. The primary endpoint was the objective response rate. Simon's optimal 2-stage design was used to test 5% versus 20% response rate with 90% power and 10% one-sided type I error rate.

The study enrolled 39 patients. Median age was 63 (range 20-80) years, 30 (77%) were male, 34 (94%) were White, and 21 (57%) had gastric tumors. The median number of cycles completed was 4.5 (range: 0-36), and 25 patients required dose reductions or discontinuation of at least one component due to toxicity. Of the 38 patients evaluable for response, 15 (42.9%) had complete/partial response (CR/PR) as the best response, and 13 (37.1%) had stable disease. progression-free survival (PFS) and OS data were available for 38 patients, with a median follow-up duration of 27 months (range: 18.2-51.9 months for censored patients). Median PFS was 6.6 months (95% CI: 5.6-12.9), with 31.0% (95% CI: 18.4%-52.4%) 12-month PFS rate. The median OS was 10.5 months (95% CI: 8.8-20.7), 12-month OS rate was 44.7% (95% CI: 31.4%-63.7%). Treatment-related grade 3-4 toxicities included peripheral sensory neuropathy and anemia (18.4% each), neutropenia (15.8%), and diarrhea and lymphopenia (7.9% each).

FOLFOX-A has a significant response rate, expected toxicities, and should be considered for future investigation in combination with immunotherapy given the recent approvals.

This study aimed to assess the safety and efficacy of generic nab-paclitaxel in the Chinese population in a real-world setting.

This prospective, multicenter, observational study enrolled patients with malignancies who received any generic nab-paclitaxel-based regimens in China. The primary endpoint was safety, and secondary endpoint was objective response rate (ORR). Logistic regression was used to explore risk factors for adverse events (AEs) of special interest (AESIs).

Between September 2019 and April 2023, 1168 patients were enrolled and evaluated for safety, and 602 were assessed for tumor response. Of 1168 patients, 169 (14.5%) received generic nab-paclitaxel monotherapy, and 999 (85.5%) received generic nab-paclitaxel-based combination therapy. Grade 3-4 AEs occurred in 19.3% (225/1168) patients, most commonly including neutrophil count decreased (7.6%), anemia (5.8%), and white blood cell decreased (5.7%). In subgroup analysis, peripheral sensory neuropathy was observed frequently in breast cancer (45.6%). Multivariate analysis showed that patients receiving combination therapy and ≥ 4 treatment cycles (OR, 1.925; 95% CI 1.363-2.719; p < 0.001) were more susceptible to the AESIs.

This study demonstrates a promising safety and efficacy of generic nab-paclitaxel-based regimens for Chinese patients with malignancies in a real-world setting, providing valuable insights for clinical decision-making.

gov NCT04060290.

According to a modern view, cancer no longer follows a purely mechanistic model. Rather, a tumor is conceived as a more complex structure, composed of cancer cells, the activities of which may interact and reshape the so-called tumor microenvironment (TME), leading to preservation of specific tumoral niches and promoting the survival of tumoral stem cells. Background/Objective: Therapeutic strategies must deal with this unique cancer architecture in the near future by widening their range of activities outside the cancer cells and rewiring a TME to ensure it is hostile to cancer growth. Therefore, an intratumoral therapeutic strategy may open the door to a new type of anticancer activity, one that directly injures the tumoral structure while also eliciting an influence on the TME through local and systemic immunomodulation. This review would like to assess the current situation of intratumoral strategies and their clinical implications. Methods We analyzed data from phase I, II, and III trials, comprehensive reviews and relevant clinical and preclinical research, from robust databases, like PUBMED, EMBASE, Cochrane Library, and clinicaltrials.gov. Results: Intratumoral strategies can be quite variable. It is possible the injection and inhalation of traditional antiblastic agents or immunomodulant agents, or intrapleural administration. Ablation strategy is available, both thermal and photodynamic method. Moreover, TTfields and NPs are analyzed and also brachytherapy is mentioned. Intratumoral therapy can find space in "adjuvant"/perioperative or metastatic settings. Finally, intratumoral strategies allow to synergize their activities with systemic therapies, guaranteeing better local and systemic disease control. Conclusions: Intratumoral strategies are overall promising. Antiblastic/immunomodulant injection and NPs use are especially interesting and intriguing. But, there is generally a lack of phase II and III trials, in particular NPs use need additional experimentation and clinical studies.

Taxol is widely used in cancer chemotherapy; however, the oral absorption of Taxol remains a formidable challenge. Since the intestinal p-glycoprotein (P-gp) mediated drug efflux is one of the primary causes, the development of P-gp inhibitor is emerging as a promising strategy to realize Taxol's oral delivery. Because P-gp exists in many tissues, the non-selective P-gp inhibitors would lead to toxicity. Correspondingly, a potent and intestine specific P-gp inhibitor would be an ideal solution to boost the oral absorption of Taxol and avoid exogenous toxicity. Herein, we would like to report a highly potent and intestine specific P-gp inhibitor to enable oral delivery of Taxol in high efficiency. Through a multicomponent reaction and post-modification, various benzofuran-fused-piperidine derivatives were achieved and the biological evaluation identified 16 c with potent P-gp inhibitory activity. Notably, 16 c was intestine specific and showed almost none absorption (F=0.82 %), but possessing higher efficacy than Encequidar to improve the oral absorption of Taxol. In MDA-MB-231 xenograft model, the oral administration of Taxol and 16 c showed high therapeutic efficiency and low toxicity, thus providing a valuable chemotherapy strategy.

We evaluated the feasibility of completing 6 cycles of nab-paclitaxel (nab-P) and carboplatin (C) in a single arm prospective clinical trial for advanced/recurrent EC and safety and efficacy of day (D) 1, 8 nab-P in combination with D1 C q3weeks.

Patients with early-stage, high-risk, advanced primary/recurrent EC without prior platinum/taxane exposure were enrolled in an open-label, single-institution trial (NCT02744898). Patients received 6 cycles of D1 nab-P 100 mg/m2 IV with C AUC 6 IV and D8 nab-P 100 mg/m2 IV q21D. The trial tested the null hypothesis that subjects completing 6 cycles was ≤0.50 versus the alternative that the proportion is ≥0.75 in a single stage design with alpha = 0.05 and power = 80% with 23 subjects. Patients who completed 6 cycles (primary outcome), objective response rate (ORR) and clinical benefit rate (CBR) were estimated with exact 95% Clopper-Pearson confidence intervals. Progression free survival (PFS) and overall survival (OS) were estimated using Kaplan-Meier methods.

From 08/2016-03/2018, 23 patients were enrolled. Nineteen patients (82.6%, 95% CI: 61.2%, 95.0%) completed 6 cycles, thus we could reject our null. Twelve patients (52.2%) experienced ≥1 grade 3/4 treatment-related adverse events including: anemia, 6 (26.1%); neutropenia, 5 (21.7%); diarrhea, 3 (13.0%). Fourteen patients (60.1%) reported grade 1 neuropathy. Of 9 patients with measurable target lesions, the ORR was 33.3% (95% CI: 7.5%, 70.1%) and CBR was 55.6% (95% CI: 21.2%, 86.3%). Median PFS in the advanced/recurrent patients was 23.2 (95% CI: 12.1, NR) months.

The nab-P/C D1, 8 regimen met pre-specified feasibility criteria with acceptable toxicity and efficacy. Use of nab-P decreases need for steroid pre-medications, and this carboplatin doublet may prove advantageous for trials assessing combinations with immune checkpoint inhibitors in advanced EC.

The LUNAR trial demonstrated the significant efficacy and safety of Tumor Treating Fields (TTFields) plus standard-of-care (SOC) [immune checkpoint inhibitor (ICI) and docetaxel (DTX)] for patients with previously treated metastatic non-small cell lung cancer (mNSCLC). However, it remains uncertain as to whether the high costs are justified by the corresponding survival benefits. Here, the cost-effectiveness of using TTFields plus SOC for treating mNSCLC was evaluated from the perspective of the Chinese healthcare system.

A Markov model with a 15-year time horizon was established and used to comparedeveloped to enable the simulation of treatment-associated costs and patient outcomes when comparing TTFields plus SOC to SOC alone. Primary outcomes for these analyses included total costs, life-years (LYs), quality-adjusted LYs (QALYs), and incremental cost-effectiveness ratio (ICER) values. The impact of paramere uncertainty on model outcomes was evaluated through sensitivity analyses. Additional subgroup and scenario analyses were also performed to extend these results.

While TTFields plus SOC exhibited a $74,688 increase in total costs relative to SOC ($96,092 vs. $21,404), it was associated with 0.38 additional QALYs (1.08 vs. 0.82 QALYs) for an ICER of $284,490/QALY. This value exceeded the $35,983/QALY willingness-to-pay (WTP) threshold selected for these analyses by a wide margin. Relative to ICI and DTX treatment, the incremental costs of TTFields plus ICI and TTFields plus DTX were $78,115 and $71,307, respectively, with corresponding gains of 0.42 and 0.13 QALYs, yielding ICERs of $187,434/QALY, and $546,386/QALY. The parameter that most strongly impacted the results of these analyses was the cost of TTFields.

The results indicated that given current treatment costs, TTFields plus SOC was insufficiently cost-effective in treating patients with mNSCLC in China, although TTFields plus ICI yields substantial health benefits.

This study aimed to evaluate the risk of adverse events (AEs) in breast cancer patients treated with pembrolizumab combined with paclitaxel versus those receiving pembrolizumab or paclitaxel monotherapy, using the FDA Adverse Event Reporting System (FAERS) database.

Data were extracted from the FAERS database for breast cancer patients treated with pembrolizumab combined with paclitaxel or with pembrolizumab or paclitaxel monotherapy from Q1 2016 to Q2 2023. Disproportionation analysis was performed by calculating the reporting odds ratio (ROR) with corresponding 95% confidence interval (95% CI), the information component (IC), and the lower bound of the information component 95% confidence interval (IC025) to identify potential safety signals.

No significant difference in AEs was observed between the combined treatment group and the pembrolizumab monotherapy group. However, the combined treatment group exhibited a substantial increase in AE risk compared to the paclitaxel monotherapy group. The most significant increases in AE risk were adrenal insufficiency (ROR = 189.94, 95% CI 25.41-1419.7, IC = 3.37, IC025 = 1.59), hypophysitis (ROR = 99.46, 95% CI 12.72-777.4, IC = 3.31, IC025 = 1.44), and myocarditis (ROR = 69.5, 95% CI 8.55-565.23, IC = 3.25, IC025 = 1.33). The time-to-event for combined treatment was 35 (34-70) days, for pembrolizumab was 43 (35-90) days, and for paclitaxel was 42 (37-76) days. The combination therapy group demonstrated significantly shorter intervals to the onset of adrenal insufficiency (p = 0.008), myocarditis (p < 0.001), and immune-related enterocolitis (p = 0.009).

Analysis of the FAERS database indicates that combination therapy significantly elevates the risk of adrenal insufficiency, myocarditis, hypophysitis, and immune-related enterocolitis compared to paclitaxel monotherapy. These findings provide critical insights for clinicians in predicting and managing potential AEs associated with this treatment regimen.

Cancer is still ranked among the top three causes of death in the 30- to 69-year-old age group in most countries and carries considerable societal and macroeconomic costs that differ depending on the cancer type, geography, and patient gender. Despite advances in several pharmacological approaches, the lack of stability and specificity, dose-related toxicity, and limited bioavailability of chemotherapy (standard therapy) pose major obstacles in cancer treatment, with multidrug resistance being a driving factor in chemotherapy failure. The past three decades have been the stage for intense research activity on the topic of nanomedicine, which has resulted in many nanotherapeutics with reduced toxicity, increased bioavailability, and improved pharmacokinetics and therapeutic efficacy employing smart drug delivery systems (SDDSs). Polymeric micelles (PMs) have become an auspicious DDS for medicinal compounds, being used to encapsulate hydrophobic drugs that also exhibit substantial toxicity. Through preclinical animal testing, PMs improved pharmacokinetic profiles and increased efficacy, resulting in a higher safety profile for therapeutic drugs. This review focuses on PMs that are already in clinical trials, traveling the pathways from preclinical to clinical studies until introduction to the market.

Paclitaxel (PTX) is a first-line drug for the treatment of lung cancer, but its targeting and therapeutic effect are unsatisfactory. Herein, lung cancer cell (A549) membrane biomimetic PTX-loaded poly (lactic-co-glycolic acid) (PLGA) nanoparticles (AM@PTX-NPs) were constructed to eliminate the shortcomings of PTX. The AM@PTX-NPs were successfully prepared with a high drug loading efficiency (10.90±0.06 %). Moreover, transmission electron microscopy, SDS-PAGE, and western blotting proved that AM@PTX-NPs were spherical nanoparticles camouflaged by the A549 cell membrane. Both in vitro and in vivo assays revealed that the AM@PTX-NPs displayed outstanding targeting capacity due to A549 membrane modification. The cytotoxicity experiment showed that the developed biomimetic formulation was able to effectively reduce the proliferation of A549 cells. Moreover, AM@PTX-NPs exhibited a significant tumor growth inhibition rate (73.00 %) with good safety in the tumor-bearing mice, which was higher than that of the PTX-NPs without A549 membrane coating (37.39 %). Overall, the constructed bioinspired vector could provide a novel platform for the PTX delivery and demonstrated a promising strategy for the targeted cancer treatment.

Esophageal cancer (EC), a prevalent malignancy, has a high incidence and mortality. X-ray repair cross complementing 2 (XRCC2) functions on DNA damage and repair that works the progression of various cancers. Nevertheless, the role and mechanism of XRCC2 remain unknown in EC. The XRCC2 expression was examined by reverse transcription quantitative polymerase chain reaction and western blot. The function of XRCC2 in EC were investigated through cell counting kit-8, colony formation, transwell, flow cytometry, chromatin immunoprecipitation, luciferase, and western blot experiments. Besides, the role of XRCC2 in EC was assessed by western blot and immunohistochemistry experiments after nude mice were injected with EC109 cells and treated with nab-paclitaxel. The XRCC2 expression was upregulated in EC. Knockdown of XRCC2 diminished cell viability, and the number of colonies, migration cells and invasion cells of KYSE150 and EC109 cells. Silencing of XRCC2 diminished the cell viability of both two cells with a lower IC50, whereas boosted the apoptosis rate of both cells with the treatment of albumin-paclitaxel. All these outcomes were reverse with the upregulation of XRCC2 in both two cells. Mechanically, XRCC2 was transcriptionally regulated by specificity protein 1 (SP1), and silencing of SP1 inhibited the cell growth of EC. In vivo, transfection of shXRCC2 with or without albumin-paclitaxel treatment both decreased the tumor size and weight, as well as the expression of XRCC2 and Ki-67 in xenografted mice. XRCC2 transcriptionally regulated by SP2 promoted proliferation, migration, invasion, and chemoresistance of EC cells.

Delivery systems based on albumin nanoparticles (NPs) have recently garnered substantial interest in anti-tumor drug development. However, systematic bibliometric analyses in this field remain lacking. This study aimed to analyze the current research status, hotspots, and frontiers in the application of albumin NPs in the field of oncology from a bibliometric perspective.

Using the Web of Science Core Collection (WOSCC) as the data source, retrieved articles were analyzed using software, such as VOSviewer 1.6.18 and CiteSpace 6.1.6, and the relevant visualization maps were plotted.

From 1 January 2000, to 15 April 2024, 2,262 institutions from 67 countries/regions published 1,624 articles related to the application of albumin NPs in the field of oncology. The USA was a leader in this field and held a formidable academic reputation. The most productive institution was the Chinese Academy of Sciences. The most productive author was Youn YS, whereas Kratz F was the most frequently co-cited author. The most productive journal was the International Journal of Nanomedicine, whereas the Journal of Controlled Release was the most co-cited journal. Future research hotspots and frontiers included "rapid and convenient synthesis methods predominated by self-assembly," "surface modification," "construction of multifunctional NPs for theranostics," "research on natural active ingredients mainly based on phenolic compounds," "combination therapy," and "clinical applications."

Based on our bibliometric analysis and summary, we obtained an overview of the research on albumin NPs in the field of oncology, identified the most influential countries, institutions, authors, journals, and citations, and discussed the current research hotspots and frontiers in this field. Our study may serve as an important reference for future research in this field.

Bevacizumab with platinum doublet therapy including paclitaxel + carboplatin improves the survival of patients with non-squamous non-small cell lung cancer. However, in a previous trial (CA031), paclitaxel + carboplatin led to Grade > 3 neutropenia in a Japanese population. Nanoparticle albumin-bound paclitaxel exhibits an improved toxicity profile. We evaluated the safety, dosage and response rate of the nanoparticle albumin-bound paclitaxel + carboplatin + bevacizumab combination in a Japanese population.

Chemotherapy-naive patients with advanced non-squamous non-small cell lung cancer were included. The dosage schedule was established in the Phase I trial as follows: 4-6 cycles of carboplatin (area under the concentration-time curve = 6 on Day 1) + nanoparticle albumin-bound paclitaxel (100 mg/m2 on Days 1, 8 and 15) + bevacizumab (15 mg/kg on Day 1), followed by maintenance therapy (nanoparticle albumin-bound paclitaxel + bevacizumab). The response rate and presence of adverse effects were evaluated in the Phase II trial.

The overall response rate was 56.5% (90% confidence interval: 44.5-68.5), and 93% of patients (43/46) showed tumor shrinkage or maintained a stable disease course. The primary endpoint was achieved. At the median follow-up duration of 42 months, the median overall survival was 18.9 (range: 10.5-32.4) months. The most frequently observed Grade ≥ 3 adverse effects were neutropenia (72%), leukopenia (50%) and anemia (30%).

All adverse effects were manageable and none resulted in patient death. In conclusion, the nanoparticle albumin-bound paclitaxel + carboplatin + bevacizumab combination is favorable and well tolerated in Japanese patients as first-line treatment for advanced non-squamous non-small cell lung cancer.

Lung cancer is associated with a high mortality rate worldwide. Non-small-cell lung cancer (NSCLC) is a major subtype of lung cancer. Carboplatin (CBDCA) plus nab-paclitaxel (PTX) has become a standard treatment for advanced unresectable NSCLC. However, treatment with nab-PTX has not been established as a standard therapy for resectable locally advanced (LA)-NSCLC.

We conducted a comprehensive study involving consecutive patients with locally advanced NSCLC who underwent induction therapy including nab-PTX followed by surgical resection. Fifteen patients with locally advanced NSCLC underwent induction therapy including nab-PTX followed by surgical resection. Concurrent chemoradiotherapy (CRT) consisted of weekly administration of nab-PTX (50 mg/m2) plus CBDCA (area under the plasma concentration time curve (AUC) 2) and thoracic radiotherapy (50 Gy/25 fractions).

The clinical stages were as follows: IIB (n =1), IIIA (n =12), and IIIC (n =2). Downstaging was observed in 73% (11/15) of patients on comparison with the clinical stage before concurrent CRT. Adverse drug reactions were observed in seven patients. Complete resection was performed in all patients. The re-evaluated pathological stage after pretreatment was diagnosed as stage 0 in three patients, stage IA1 in six, stage IA2 in one, and stage IIIA in five. The pathological effects of previous therapy were as follows: Ef3 (n =3), Ef2 (n =9), and Ef1a (n =3).

The therapeutic effect of induction therapy including nab-PTX was promising. Induction CRT, including nab-PTX, followed by resection, may be a viable alternative treatment option for locally advanced NSCLC.

To compare the effectiveness and safety of nab-paclitaxel, cisplatin, and capecitabine (nab-TPC) with gemcitabine and cisplatin as an alternative first line treatment option for recurrent or metastatic nasopharyngeal carcinoma.

Phase 3, open label, multicentre, randomised trial.

Four hospitals located in China between September 2019 and August 2022.

Adults (≥18 years) with recurrent or metastatic nasopharyngeal carcinoma.

Patients were randomised in a 1:1 ratio to treatment with either nab-paclitaxel (200 g/m2 on day 1), cisplatin (60 mg/m2 on day 1), and capecitabine (1000 mg/m2 twice on days 1-14) or gemcitabine (1 g/m2 on days 1 and 8) and cisplatin (80 mg/m2 on day 1).

Progression-free survival was evaluated by the independent review committee as the primary endpoint in the intention-to-treat population.

The median follow-up was 15.8 months in the prespecified interim analysis (31 October 2022). As assessed by the independent review committee, the median progression-free survival was 11.3 (95% confidence interval 9.7 to 12.9) months in the nab-TPC cohort compared with 7.7 (6.5 to 9.0) months in the gemcitabine and cisplatin cohort. The hazard ratio was 0.43 (95% confidence interval 0.25 to 0.73; P=0.002). The objective response rate in the nab-TPC cohort was 83% (34/41) versus 63% (25/40) in the gemcitabine and cisplatin cohort (P=0.05), and the duration of response was 10.8 months in the nab-TPC cohort compared with 6.9 months in the gemcitabine and cisplatin cohort (P=0.009). Treatment related grade 3 or 4 adverse events, including leukopenia (4/41 (10%) v 13/40 (33%); P=0.02), neutropenia (6/41 (15%) v 16/40 (40%); P=0.01), and anaemia (1/41 (2%) v 8/40 (20%); P=0.01), were higher in the gemcitabine and cisplatin cohort than in the nab-TPC cohort. No deaths related to treatment occurred in either treatment group. Survival and long term toxicity are still being evaluated with longer follow-up.

The nab-TPC regimen showed a superior antitumoural efficacy and favourable safety profile compared with gemcitabine and cisplatin for recurrent or metastatic nasopharyngeal carcinoma. Nab-TPC should be considered the standard first line treatment for recurrent or metastatic nasopharyngeal carcinoma. Longer follow-up is needed to confirm the benefits for overall survival.

Chinese Clinical Trial Registry ChiCTR1900027112.

The treatment landscape of non-small cell lung cancer (NSCLC) has seen significant advancements in recent years, marked by a shift toward target agents and immune checkpoint inhibitors (ICIs). However, chemotherapy remains a cornerstone of treatment, alone or in combination. Microtubule-targeting agents, such as taxanes and vinca alkaloids, play a crucial role in clinical practice in both early and advanced settings in NSCLC.

This review outlines the mechanisms of action, present significance, and prospective advancements of microtubule-targeting agents (MTAs), with a special highlight on new combinations in phase 3 trials. The online databases PubMed, Web of Science, Cochrane Library, and ClinicalTrials.gov were searched using the terms 'Microtubule-targeting agents' and 'non-small cell lung cancer' or synonyms, with a special focus over the last 5 years of publications.

Despite the emergence of immunotherapy, MTA remains crucial, often used alongside or after immunotherapy, especially in squamous cell lung cancer. Next-generation sequencing expands treatment options, but reliable biomarkers for immunotherapy are lacking. While antibody-drug conjugates (ADCs) show promise, managing toxicities remain vital. In the early stages, MTAs, possibly with ICIs, are standard, while ADCs may replace traditional chemotherapy in the advanced stages. Nevertheless, MTAs remain essential in subsequent lines or for patients with contraindications.

Aim: This study aimed to improve comparative effectiveness estimates and discuss challenges encountered through the application of Bayesian borrowing (BB) methods to augment an external control arm (ECA) constructed from real-world data (RWD) using historical clinical trial data in first-line non-small-cell lung cancer (NSCLC). Materials & methods: An ECA for a randomized controlled trial (RCT) in first-line NSCLC was constructed using ConcertAI Patient360™ to assess chemotherapy with or without cetuximab, in the bevacizumab-inappropriate subpopulation. Cardinality matching was used to match patient characteristics between the treatment arm (cetuximab + chemotherapy) and ECA. Overall survival (OS) was assessed as the primary outcome using Cox proportional hazards (PH). BB was conducted using a static power prior under a Weibull PH parameterization with borrowing weights from 0.0 to 1.0 and augmentation of the ECA from a historical control trial. Results: The constructed ECA yielded a higher overall survival (OS) hazard ratio (HR) (HR = 1.53; 95% CI: 1.21-1.93) than observed in the matched population of the RCT (HR = 0.91; 95% CI: 0.73-1.13). The OS HR decreased through the incorporation of BB (HR = 1.30; 95% CI: 1.08-1.54, borrowing weight = 1.0). BB was applied to augment the RCT control arm via a historical control which improved the precision of the observed HR estimate (1.03; 95% CI: 0.86-1.22, borrowing weight = 1.0), in comparison to the matched population of the RCT alone. Conclusion: In this study, the RWD ECA was unable to successfully replicate the OS estimates from the matched population of the selected RCT. The inability to replicate could be due to unmeasured confounding and variations in time-periods, follow-up and subsequent therapy. Despite these findings, we demonstrate how BB can improve precision of comparative effectiveness estimates, potentially aid as a bias assessment tool and mitigate challenges of traditional methods when appropriate external data sources are available.

Kaposi sarcoma (KS) incidence has decreased since the initiation of combination antiretroviral therapy (cART), but it remains the most common cancer in people with HIV/AIDS (PWHA). PWHA with advanced immunosuppression who initiate antiretroviral therapy are susceptible to the occurrence of an immune reconstitution inflammatory syndrome (IRIS).

This report covers the case of a 25-year-old male with AIDS-related KS who relapsed after Liposomal Doxorubicin, but recovered well after administration of nab-paclitaxel (Nab-PTX).

This is a rare case in choosing Nab-PTX to treat relapsed AIDS-KS and get good feedback. We report the case to provide a possible solution to treat AIDS-KS.

Combination of chidamide and anti-PD-L1 inhibitor produce synergistic anti-tumor effect in advanced NSCLC patients resistant to anti-PD-1 treatment. However, the effect of chidamide plus envafolimab has not been reported.

This study aimed to evaluate the efficacy of chidamide plus envafolimab in advanced NSCLC patients resistant toanti-PD-1 treatment.

Eligible advanced NSCLC patients after resistant to anti-PD-1 therapy received chidamide and envafolimab. The primary endpoint was objective response rate (ORR). The secondary end points included disease control rate (DCR), progression-free survival (PFS), and safety. The expression of histone deacetylase 2 (HDAC2), PD-L1, and blood TMB (bTMB) was also analyzed.

After a median follow-up of 8.1 (range: 7.6-9.2) months, only two patients achieved partial response. The ORR was 6.7% (2/30), DCR was 50% (15/30), and median PFS (mPFS) was 3.5 (95% confidence interval: 1.9-5.5) months. Biomarker analysis revealed that patients with high-level HDAC2 expression had numerically superior ORR (4.3% vs. 0), DCR (52.2% vs. 0) and mPFS (3.7 vs. 1.4m). Patients with negative PD-L1 had numerically superior DCR (52.2% vs. 33.3%) and mPFS (3.7m vs. 1.8m), so were those with low-level bTMB (DCR: 59.1% vs. 16.7%, mPFS: 3.8 vs.1.9m). Overall safety was controllable.

High HDAC2patients showed better ORR, DCR, and PFS. In addition, patient with negative PD-L1 and low-level bTMB had better DCR and PFS. This may be related to the epigenetic function of chidamide. However, the sample size was not big enough, so it is necessary to increase sample size to confirm the conclusion.

Combination of chidamide and envafolimab showed efficacy signals in certain NSCLC patients. But further identification of beneficial population is necessary for precision treatment.

The bioactive components of microbial origin have been extensively applied to restrict the enormous enzyme-catalyzed processes. Hence, the present study was executed to explore the α -amylase inhibition (AAI) potential of glycoprotein isolated from Lactobacillus delbrueckii (LGp) to regulate in vitro starch hydrolysis. As a non-competitive inhibitor, the protein exhibited AAI (85%) with, IC50 135 ± 0.55 μg/mL. It was stable over a broad range of pH (3-11) and temperature (25-75 °C). Furthermore, LGp was significantly effective against amylase and starch from different sources. In addition, it also exhibited antioxidant and emulsifying potential. The UV, FT-IR and fluorescence analysis affirm the alterations in amylase molecular conformation after interaction with the LGp inhibitor. These results provide a substantial basis for the future use of LGp for controlled starch hydrolysis in vitro and as an antioxidant and emulsifying agent in the food industry.

Tumor-treating field (TTFields) was a novel antitumor therapy that provided significant survival for previously treated metastatic non-small cell lung cancer (mNSCLC). The consistency of the cost of the new treatment regimen with its efficacy was the main objective of the study.

The primary parameters, derived from the Phase 3 LUNAR study, were collected to evaluate the cost and efficacy of TTFields plus standard-of-care (SOC) (immune checkpoint inhibitors [ICIs] and docetaxel [DTX]) or SOC in patients with mNSCLC by establishing a three-state Markov model over a 15-year time horizon. Primary outcome measures for this study included costs, life-years (LYs), quality-adjusted LYs (QALYs), and incremental cost-effectiveness ratios (ICERs). Sensitivity analyses were performed.

The total costs of TTFields plus SOC, TTFields plus ICI, and TTFields plus DTX were $319,358, $338,688, and $298,477, generating 1.23 QALYs, 1.58 QALYs, and 0.89 QALYs, respectively. The ICERs of TTFields plus SOC versus SOC, TTFields plus ICI versus ICI, and TTFields plus DTX versus DTX were $613,379/QALY, $387,542/QALY, and $1,359,559/QALY, respectively. At willingness-to-pay (WTP) thresholds of $150,000/QALY, the probability of combination TTFields being cost-effective was 0%. In addition, TTFields plus SOC exhibited similar efficacy (1.12 QALYs and 1.14 QALYs) and costs ($309,822 and $312,531) in the treatment of squamous cell carcinoma (SCC) and non-squamous cell carcinoma (NSCC) populations.

In the United States, TTFields plus SOC as second-line treatment was not a more cost-effective strategy for patients with mNSCLC. Of the analyzed regimens, TTFields plus ICI was associated with most significant health benefits.

Paclitaxel is an effective chemotherapeutic agent against a variety of cancer types. However, the clinical utility of paclitaxel is restricted by its poor solubility in water and high toxicity, resulting in low drug tolerance. These difficulties could be resolved by using suitable pharmacological carriers. Hence, it is essential to determine innovative methods of administering this effective medication to overcome paclitaxel's inherent limitations.

An extensive literature search was conducted using multiple electronic databases to identify relevant studies published.

In this comprehensive analysis, many different paclitaxel delivery systems are covered and discussed, such as albumin-bound paclitaxel, polymeric micelles, paclitaxel-loaded liposomes, prodrugs, cyclodextrins, and peptide-taxane conjugates. Moreover, the review also covers various delivery routes of conventional paclitaxel or novel paclitaxel formulations, such as oral administration, local applications, and intraperitoneal delivery.

In addition to albumin-bound paclitaxel, polymeric micelles appear to be the most promising formulations for innovative drug delivery systems at present. A variety of variants of polymeric micelles are currently undergoing advanced phases of clinical trials.

We evaluated the effect of high-dose polymeric nanoparticle micellar paclitaxel (PM-Pac) on survival in patients with stage III-IV high-grade serous ovarian cancer (HGSC) who underwent upfront surgery.

We prospectively recruited the patients who received PM-Pac (280 mg/m2) and carboplatin at an area under the curve (AUC) of 5 (cohort 1) in two tertiary centers between October 2015 and June 2019. As historical controls, we retrospectively collected data on those who received paclitaxel (175 mg/m2) and carboplatin (AUC 5; cohort 2) or paclitaxel (175 mg/m2), carboplatin (AUC 5) and bevacizumab (15 mg/kg; cohort 3).

A total of 128 patients were divided into cohorts 1 (n=49, 38.3%), 2 (n=53, 41.4%), and 3 (n=26, 20.3%). Cohort 1 showed better progression-free survival (PFS) than cohort 2 in all patients and those treated with optimal debulking surgery (ODS; median, 35.5 vs. 28.1 and 35.5 vs. 28.9 months; p ≤ 0.01) despite no difference in PFS between cohorts 1 and 3 and between cohorts 2 and 3. In particular, stage III disease was a favorable factor for PFS, whereas cohort 2 was related to worse PFS (adjusted hazard ratios, 0.456 and 1.834; 95% confidence interval, 0.263 - 0.790 and 1.061 - 3.171), showing no difference in PFS between cohorts 1 and 3 in those treated with ODS.

High-dose PM-Pac improved PFS compared to conventional chemotherapy, and the change of paclitaxel to PM-Pac had as much effect on PFS as the addition of bevacizumab in patients with stage III-IV HGSC who underwent ODS.