Liposomal Doxorubicin Hydrochloride Research Articles

Albumin Nanoparticles Increase the Efficacy of Doxorubicin Hydrochloride Liposome Injection Based on Threshold Theory.

One of the most significant reasons hindering the clinical translation of nanomedicines is the rapid clearance of intravenously injected nanoparticles by the mononuclear phagocyte system, particularly by Kupffer cells in the liver, leading to an inefficient delivery of nanomedicines for tumor treatment. The threshold theory suggests that the liver's capacity to clear nanoparticles is limited, and a single high dose of nanoparticles can reduce the hepatic clearance efficiency, allowing more nanomedicines to reach tumor tissues and enhance therapeutic efficacy. Building upon this theory, researchers have conducted numerous validation studies based on the same nanoparticle carrier systems. These studies involve the use of albumin nanoparticles to improve the therapeutic efficacy of albumin nanomedicines as well as polyethylene glycol (PEG)-modified liposomal nanoparticles to enhance the efficacy of PEGylated liposomal nanomedicines. However, there is no research indicating the feasibility of the threshold theory when blank nanoparticles and nanomedicine belong to different nanoparticle carrier systems currently. In this study, we prepared two different sizes of albumin nanoparticles by using bovine serum albumin. We used the marketed nanomedicine liposomal doxorubicin hydrochloride injection (trade name: LIBOD, manufacturer: Shanghai Fudan-zhangjiang Biopharmaceutical Co., Ltd.), as the representative nanomedicine. Through in vivo experiments, we found that using threshold doses of albumin nanoparticles still can reduce the clearance rate of LIBOD, prolong its time in vivo, increase the area under the plasma concentration-time curve (AUC), and also lead to an increased accumulation of the drug at the tumor site. Furthermore, evaluation of in vivo efficacy and safety further indicates that threshold doses of 100 nm albumin nanoparticles can enhance the antitumor effect of LIBOD without causing harm to the animals. During the study, we found that the particle size of albumin nanoparticles influenced the in vivo distribution of the nanomedicine at the same threshold dose. Compared with 200 nm albumin nanoparticles, 100 nm albumin nanoparticles more effectively reduce the clearance efficiency of LIBOD and enhance nanomedicine accumulation at the tumor site, warranting further investigation. This study utilized albumin nanoparticles to reduce hepatic clearance efficiency and enhance the delivery efficiency of nonalbumin nanocarrier liposomal nanomedicine, providing a new avenue to improve the efficacy and clinical translation of nanomedicines with different carrier systems.

An Automated Capillary Electrophoresis Based Method for Drug Release Profiling of Liposomal Doxorubicin

Liposomal doxorubicin hydrochloride is an antineoplastic agent widely used against human cancers. The data from in vitro drug release test (IVRT) is essential for quality and/or bioequivalence evaluation in drug approval and post-approval regulation of liposomal drug products. However, most of the currently available IVRT methods for liposomal doxorubicin hydrochloride have experimental deficiencies associated with liposomal rupture during the separation process which is needed for selective quantification of released drug from liposomal-bound drug. In addition, many of the methods are time consuming, requiring bulk quantities of liposomal drug product, and lack of automation. We have developed a selective, sensitive, and automated capillary electrophoresis (CE)-based IVRT method, measuring released doxorubicin without additional sampling and separation steps. This method requires a small volume of sample compared to currently available methods. The IVRT release study with liposomal doxorubicin was conducted at different temperatures and pH conditions. It was observed that the release profiles obtained for five formulations including the reference listed drug were similar at pH 6.50 and 47.0 °C. The drug release increased with the increase of media pH and temperature. Complete doxorubicin release (100 %) was obtained in 7 h at pH 6.50 and 47.0 °C, and in less than 3 h at pH 6.50 and 52.0 °C. This CE-based method can be extended for determination of the IVRT profiling of other liposomal drug products.

Pneumocystis jirovecii with high probability detected in bronchoalveolar lavage fluid of chemotherapy-related interstitial pneumonia in patients with lymphoma using metagenomic next-generation sequencing technology

BackgroundPrevious studies achieved low microbial detection rates in lymphoma patients with interstitial pneumonia (IP) after chemotherapy. However, the metagenomic next-generation sequencing (mNGS) is a comprehensive approach that is expected to improve the pathogen identification rate. Thus far, reports on the use of mNGS in lymphoma patients with chemotherapy-related IP remain scarce. In this study, we summarized the microbial detection outcomes of lymphoma patients with chemotherapy-related IP through mNGS testing of bronchoalveolar lavage fluid (BALF).MethodsFifteen lymphoma patients with chemotherapy-related IP were tested for traditional laboratory microbiology, along with the mNGS of BALF. Then, the results of mNGS and traditional laboratory microbiology were compared.ResultsOf the 15 enrolled patients, 11 received rituximab and 8 were administered doxorubicin hydrochloride liposome. The overall microbial yield was 93.3% (14/15) for mNGS versus 13.3% (2/15) for traditional culture methods (P ≤ 0.05). The most frequently detected pathogens were Pneumocystis jirovecii (12/15, 80%), Cytomegalovirus (4/15, 26.7%), and Epstein-Barr virus (3/15, 20%). Mixed infections were detected in 10 cases. Five patients recovered after the treatment with antibiotics alone without glucocorticoids.ConclusionOur findings obtained through mNGS testing of BALF suggested a high microbial detection rate in lymphoma patients with IP after chemotherapy. Notably, there was an especially high detection rate of Pneumocystis jirovecii. The application of mNGS in patients with chemotherapy-related IP was more sensitive.

Effect of Composition and Size on Surface Properties of Anti-Cancer Nanoparticles.

Liposomal formulations offer significant advantages as anticancer drug carriers for targeted drug delivery; however, due to their complexity, clinical translation has been challenging. In addition, liposomal product manufacturing has been interrupted in the past, as was the case for Doxil® (doxorubicin hydrochloride liposome injection). Here, interfacial tension (IFT) measurements were investigated as a potential physicochemical characterization tool to aid in liposomal product characterization during development and manufacturing. A pendant drop method using an optical tensiometer was used to measure the interfacial tension of various analogues of Doxil® liposomal suspensions in air and in dodecane. The effect of liposome concentration, formulation (PEG and cholesterol content), presence of encapsulated drug, as well as average particle size was analyzed. It was observed that Doxil® analog liposomes demonstrate surfactant-like behavior with a sigmoidal-shape interfacial tension vs. concentration curve. This behavior was heavily dependent on PEG content, with a complete loss of surfactant-like behavior when PEG was removed from the formulation. In addition to interfacial tension, three data analyses were identified as able to distinguish between formulations with variations in PEG, cholesterol, and particle size: (i) polar and non-polar contribution to interfacial tension, (ii) liposomal concentration at which the polar and non-polar components were equal, and (iii) rate of interfacial tension decay after droplet formation, which is indicative of how quickly liposomes migrate from the bulk of the solution to the surface. We demonstrate for the first time that interfacial tension can be used to detect certain liposomal formulation changes, such as PEG content, encapsulated drug presence, and size variability, and may make a useful addition to physicochemical characterization during development and manufacturing of liposomal products.

Retracted: Effect of Paclitaxel Combined with Doxorubicin Hydrochloride Liposome Injection in the Treatment of Osteosarcoma and MRI Changes before and after Treatment.

[This retracts the article DOI: 10.1155/2022/5651793.].

Microwave ablation combined with transarterial chemoembolization containing doxorubicin hydrochloride liposome for treating primary and metastatic liver cancers

AimsTo determine the safety and efficacy of microwave ablation (MWA) and transarterial chemoembolization (TACE) with doxorubicin hydrochloride liposome (DHL) in patients with primary liver cancer (PLC) and metastatic liver cancer (MLC). Materials and methodsThe medical records of patients with primary or metastatic liver cancer who underwent MWA combined with TACE containing DHL from March 2019 to March 2022 were collected and analyzed. Treatment-related adverse events (AEs) were recorded. Local tumor response was evaluated according to the modified RECIST criteria. Local tumor progression-free survival (LTPFS) and overall survival (OS) were calculated using the Kaplan-Meier method. ResultsAltogether, 96 patients with liver cancer were included (PLC, n ​= ​45; MLC, n ​= ​51). Forty (41.7%) patients experienced AEs during treatment, and eight (8.3%) patients developed grade 3 AEs. Compared to before treatment, the serum total bilirubin level and neutrophil to lymphocyte ratio significantly increased after treatment. The median LTPFS was 14.5 months in patients with PLC and 10.7 months in patients with MLC. The median OS was not reached in patients with PLC or MLC. The 1-month and 3-month disease control rates reached more than 80% in both groups. ConclusionMWA combined with TACE with DHL may be a safe and effective method for the treatment of liver cancer.

Development and validation of an LC-MS/MS method for the quantification of free and total doxorubicin in human plasma and its clinical application for a novel doxorubicin hydrochloride liposome injection in Chinese patients with breast cancer

AbstractA novel doxorubicin hydrochloride liposome injection was prepared to reduce toxicity and side effects, as well as extend plasma half-life in the treatment of breast cancer. In this study, a rapid and sensitive bioanalytical method was developed and validated to characterize the pharmacokinetic profile of total and free doxorubicin in plasma of 3 Chinese patients after intravenous infusion of this injection. Plasma samples were prepared by protein precipitation for the determination of total doxorubicin, while solid phase extraction was used to determine free doxorubicin. After plasma sample pre-treatment, total and free concentrations were quantified individually using a validated LC-MS/MS method. The calibration curves were found to be linear in the range of 0.20–500.0 ng mL−1 for total doxorubicin and in the range of 1.00–1,000 ng mL−1 for free doxorubicin. The free concentrations in plasma were only one sixth to one quarter of the total levels. Liposomal doxorubicin had a longer apparent half-life (>50 h) than the non-targeted drug (<10 h) reported in the reference. and a lower volume of distribution. This novel injectable formulation steadily released free doxorubicin from liposomes over a long period of time to reduce cardiac toxicity and side effects, while ensuring a clinical curative effect.

Pegylated liposomal doxorubicin (Duomeisu®) monotherapy in patients with HER2-negative metastatic breast cancer heavily pretreated with anthracycline and taxanes: a single-arm, phase II study

PurposeTo evaluate the efficacy and safety of pegylated liposomal doxorubicin (PLD) in patients with human epidermal growth factor receptor 2 (HER2)-negative metastatic breast cancer (MBC) heavily pretreated with anthracycline and taxanes.MethodsIn this single-arm, phase II study, patients with HER2-negative MBC previously treated with anthracycline and taxanes as second- to fifth chemotherapy received PLD (Duomeisu®, generic doxorubicin hydrochloride liposome) 40 mg/m2 every 4 weeks until disease progression, unacceptable toxicity, or completion of six cycles. Primary endpoint was progression-free survival (PFS). Secondary endpoints included overall survival (OS), objective response rate (ORR), disease control rate (DCR), clinical benefit rate (CBR), and safety.ResultsOf 44 enrolled patients (median age, 53.5 years; range, 34–69), 41 and 36 were evaluable for safety and efficacy, respectively. In total, 59.1% (26/44) of patients had ≥ 3 metastatic sites, 86.4% (38/44) had visceral disease, and 63.6% (28/44) had liver metastases. Median PFS was 3.7 months (95% confidence interval [CI] 3.3–4.1) and median OS was 15.0 months (95% CI 12.1–17.9). ORR, DCR, and CBR were 16.7%, 63.9%, and 36.1%, respectively. The most common adverse events (AEs) were leukopenia (53.7%), fatigue (46.3%), and neutropenia (41.5%), with no grade 4/5 AEs. The most common grade 3 AEs were neutropenia (7.3%) and fatigue (4.9%). Patients experienced palmar-plantar-erythrodysesthesia (24.4%, 2.4% grade 3), stomatitis (19.5%, 7.3% grade 2), and alopecia (7.3%). One patient displayed a left ventricular ejection fraction decline of 11.4% from baseline after five cycles of PLD therapy.ConclusionPLD (Duomeisu®) 40 mg/m2 every 4 weeks was effective and well-tolerated in patients with HER2-negative MBC heavily pretreated with anthracycline and taxanes, revealing a potentially viable treatment option for this population.Trial registration Chinese Clinical Trial Registry: ChiCTR1900022568.

A multicenter randomized trials to compare the bioequivalence and safety of a generic doxorubicin hydrochloride liposome injection with Caelyx ® in advanced breast cancer.

To compare the pharmacokinetic (PK) bioequivalence (BE) and safety of a generic pegylated liposomal doxorubicin (PLD) formulation with the reference product Caelyx®. A multicenter, single-dose, open-label, randomized, two-way crossover study was conducted in patients with breast cancer. For each period, the patients were administered with the test or the reference PLD intravenously at a dose of 50 mg/m2. Cmax, AUC0-t and AUC0-∞ for free, and encapsulated doxorubicin (doxorubicin) and partial AUC (AUC0-48h, AUC48h-t) for encapsulated doxorubicin were evaluated in 17 blood samples taken predose, and increasing time intervals over the following 14 days in each period. A washout period of 28-35 days was observed before crossing over. 48 patients were enrolled and randomised, of which 44 were included and analysed in bioequivalence set (BES). The 90% confidence intervals (CIs) of the geometric mean ratio (GMR) of Cmax, AUC0-t and AUC0-∞ for free doxorubicin and encapsulated doxorubicin all fall within the bioequivalent range of 80% to 125%. The 90% CIs of GMR of partial AUC (AUC0-48h, AUC48h-t) for encapsulated doxorubicin also fall within the bioequivalent range. 48 patients were all included in the safety set (SS). The incidence of treatment-emergent adverse events (TEAEs) related to T and R was 95.8% (46/48) and 97.8% (45/46) respectively. The highest incidence of TEAEs was various laboratory abnormalities. 2 patients withdrew due to T-drug-related AEs. Only one patient experienced serious adverse events and no death occurred in this study. There were no significant differences between the safety profiles of the generic formulation and Caelyx®. Bioequivalence between the test and the reference products was established for free and encapsulated doxorubicin. http://www.chinadrugtrials.org.cn, identifier [CTR20210375].

Effect of Paclitaxel Combined with Doxorubicin Hydrochloride Liposome Injection in the Treatment of Osteosarcoma and MRI Changes before and after Treatment.

Objective The aim of this study is to investigate the effect of paclitaxel combined with doxorubicin hydrochloride liposome injection (DHLI) in the treatment of osteosarcoma and the MRI changes before and after treatment. Methods A total of 108 osteosarcoma patients treated in our hospital (January 2020–April 2022) were selected to carry out a single-center retrospective study. Among them, 54 patients receiving the combination chemotherapy (MDT) with high-dose methotrexate, ifosfamide, cisplatin, and ADM were selected as the control group (COG), while 54 patients receiving MDT with high-dose methotrexate, ifosfamide, cisplatin, paclitaxel, and DHLI were chosen as the study group (STG). The COG and STG had the same dose intensity and chemotherapy cycles, and clinical and MRI evaluations were performed after treatment. Results The evaluation of postoperative clinical efficacy showed that the disease control rate (DCR) of the STG was markedly higher than that of the COG (P < 0.05). The incidence of cardiac toxicity was remarkably lower in the STG than that in the COG (P < 0.05), with no between-group differences in the incidence of fever, abnormal liver function, myelosuppression, stomatitis, and alopecia (P > 0.05). Obvious differences were found in the semiquantitative parameters of MRI in the STG before and after chemotherapy (P < 0.05) and were also found in the SImax, TTP, SEE, PPE, WOR, and R values in the COG before and after chemotherapy (P < 0.05). After chemotherapy, statistical differences were observed in the semiquantitative parameters of MRI between the two groups, with lower parameters such as Slope, SImax, SEE, and R values and higher parameters such as TTP, PPE, and WOR values in the STG than those in the COG (P < 0.05). Conclusion Paclitaxel combined with DHLI has definite efficacy in osteosarcoma chemotherapy, which is conducive to narrowing the lesion, controlling the disease, and reducing the occurrence of cardiac-related risk events. In addition, the semiquantitative parameters of dynamic contrast-enhanced MRI (DCE-MRI) have a high predictive value for the efficacy of chemotherapy, which can reflect the degree of tumor necrosis and contribute to a timely and objective assessment of the efficacy of osteosarcoma chemotherapy.

Taxane monotherapy regimens for the treatment of recurrent epithelial ovarian cancer.

Taxane monotherapy regimens for the treatment of recurrent epithelial ovarian cancer.

Bioequivalence of a hybrid pegylated liposomal doxorubicin hydrochloride injection and Caelyx®: A single-dose, randomized, multicenter, open-label, two-period crossover study in patients with advanced ovarian cancer

ObjectiveTo evaluate the bioequivalence of a hybrid pegylated liposomal doxorubicin (PLD) hydrochloride injection with reference product Caelyx®. MethodsThis multicenter, open-label, balanced, randomized, two-treatment, two-period, two-sequence, single-dose, crossover, bioequivalence study was conducted in female patients aged ≥18 years and ≤75 years with ovarian cancer, whose disease progressed or recurred after platinum-based chemotherapy, and who were scheduled to start PLD therapy. Patients were intravenously infused drugs over 1 h at 50 mg/m2 dose two hours after breakfast on the first day of the chemotherapy cycle in period-I and crossed over to the other arm in period-II (day 29). Pharmacokinetic (PK) analyses were performed using two separate, validated liquid chromatography-mass spectrometry methods for encapsulated and unencapsulated doxorubicin. ResultsBoth the test and reference formulations were well-tolerated and safe. The pharmacokinetic analysis for both encapsulated and unencapsulated doxorubicin was conducted in 50 patients and PK parameters were found to be comparable between test and reference products. The geometric mean ratios (90% confidence interval) of hybrid PLD/Caelyx® were; maximum measured plasma concentration (Cmax): 91.94-97.28%, area under the plasma concentration versus time from time 0 to t (AUC0-t): 95.19-103.67%, AUC from time 0 to ∞ (AUC0-∞): 95.13-103.66% for encapsulated doxorubicin and for unencapsulated doxorubicin Cmax: 92.08-116.46%, AUC0-t: 91.91-108.28%, AUC0-∞: 93.45-110.05%. ConclusionThe PLD formulation was found to be bioequivalent to Caelyx®.

Enhanced Therapeutic Efficacy of Combining Losartan and Chemo-Immunotherapy for Triple Negative Breast Cancer.

Triple-negative breast cancer (TNBC) is a particularly aggressive subtype of breast cancer, which is relatively resistant to anti-programmed cell death-1 (α-PD1) therapy, characterized as non-immunogenic, dense stroma and accumulation of M2 tumor-associated macrophages (TAMs). Despite progress in strategies to deplete extracellular matrix (ECM) and enhance tumor-cell immunogenicity, the combinatorial anti-cancer effects with α-PD1 need to be explored. Here, we applied doxorubicin hydrochloride liposome (Dox-L) as immunogenic cell death (ICD)-inducing nano-chemotherapy and used losartan as stroma-depleting agent to improve α-PD1 efficacy (Losartan + Dox-L + α-PD1). The results showed that losartan could cause ECM reduction, facilitating enhanced delivery of Dox-L and further dendritic cell (DC) maturation. Additionally, losartan could also alleviate hypoxia for TNBC, thus reprogramming pro-cancer M2 TAMs to anti-cancer M1 TAMs, successfully overcoming immune-suppressive microenvironment. These modifications led to a significant increase in T cells’ infiltration and augmented anti-tumor immunity as exemplified by the notable reduction in tumor size and lung metastases. In summary, our findings support that combined treatment of losartan with Dox-L normalizes immunological-cold microenvironment, improves immuno-stimulation and optimizes the efficacy of TNBC immunotherapy. A novel combinational strategy with FDA-approved compounds proposed by the study may potentially be useful in TNBC clinical treatment.

Evaluation of the Preventive Effect of Regional Cooling Nursing on Hand Foot Syndrome Caused by Doxorubicin Hydrochloride Liposome

Purpose: To explore the preventive effect of Regional cooling comprehensive nursing on hand foot syndrome caused by pegylated liposomal doxorubicin (PLD). Method: Adopt overall sampling method. Patients who used the same adjuvant drugs from January to December 2020 were randomly divided into an intervention group and a control group. The patients in the two groups received routine nursing guidance and drug prevention for the use of amygdalin. The patients in the intervention group were required to take protective measures of Regional cooling during chemotherapy. The occurrence of hand foot syndrome during adriamycin liposome administration was compared between the two groups. Results: By comparing the adverse reactions of cases during Adriamycin Administration, the incidence rates of grade I, II and III hand foot syndrome in the control group were 28.8%, 7.6% and 27.5% respectively, and the incidence rates of grade I, II and III hand foot syndrome in the intervention group were 42.1%, 12.3% and 7.0% respectively, with statistical significance (P < 0.05). Conclusion: Regional cooling nursing and preventive behavior guidance can effectively reduce the severity of hand foot syndrome caused by adriamycin.

The effectiveness of liposomal doxorubicin hydrochloride in combination with cyclophosphan in the treatment of breast cancer in an experiment

Purpose of the study. To evaluate the antitumor efficacy of liposomal doxorubicin hydrochloride in combination with tamoxifen in the treatment of breast cancer.Materials and methods. The study included mongrel white rats (n = 30). A model of carcinogenesis (Walker 256 tumors) was created for all animals. Then we divided these rats into 3 equal groups: 1 control group (n = 10) - animals were monitored without treatment; 2 group (n = 10) - animals received neoadjuvant therapy: liposomal doxorubicin hydrochloride + cyclophosphan; 3 group (n = 10) - animals received neoadjuvant therapy with doxorubicin hydrochloride (non-liposomal) and cyclophosphan. Animals of the second and third groups received two cycles of neoadjuvant therapy. All animals were monitored for 1.5 months. We evaluated the effectiveness of antitumor therapy by measuring the size of tumors, the dynamics of their regression, and counting the number of metastases in the lungs. The toxic effects of doxorubicin hydrochloride were assessed by blood parameters: platelet and lymphocyte levels.Results. We recorded a significant inhibition of the growth of tumor nodes in the second group of rats on the 25th day from the start of the experiment compared with the first and third groups: 36004.7, 86112.1 and 38962.4 mm3, respectively. By the end of the 3rd week of the experiment, we also noted the formation of a tumor regression trend in the 2nd and 3rd groups of animals, which was reliably maintained until the end of the observation. At the end of the experiment, the number of metastases in the first group of animals was 3 times more, in the third group almost 1.5 times more than in the second (p &lt; 0.05)Conclusion. The treatment of Walker 256 tumor with liposomal doxorubicin showed better efficacy and safety in comparison with non-liposomal doxorubicin. The tumor volume becomes smaller against the background of neoadjuvant chemotherapy with liposomal doxorubicin hydrochloride compared with its non-liposomal form, while there is no pronounced decrease in platelets and lymphocytes. We also recorded a significantly lower number of lung metastases in animals of the second group compared to other groups.

Irinotecan Plus Doxorubicin Hydrochloride Liposomes for Relapsed or Refractory Wilms Tumor.

PurposeThe prognosis of relapsed or refractory pediatric Wilms tumor (WT) is dismal, and new salvage therapies are needed. This study aimed to evaluate the efficacy of the combination of irinotecan and a doxorubicin hydrochloride liposome regimen for relapsed or refractory pediatric WT.Patients and MethodsThe present study enrolled relapsed or refractory pediatric WT patients who were treated with the AI regimen (doxorubicin hydrochloride liposomes 40 mg/m2 per day, day 1, and irinotecan 50 mg/m2 per day with 90-min infusion, days 1–5; this regimen was repeated every 3 weeks) at Sun Yat-sen University Cancer Center from July 2018 to September 2020. The response was defined as the best-observed response after at least two cycles according to the Response Evaluation Criteria of Solid Tumors (RECIST 1.1), and toxicity was evaluated according to the Common Terminology Criteria for Adverse Events (CTCAE 4.03).ResultsA total of 16 patients (male:female, 8:8) with a median age of 4.2 years (0.5–11 years) with relapsed or refractory disease were enrolled in this study, including 14 patients with relapsed disease and two patients with refractory disease. These patients received 1–8 courses (median, 3 courses) of the AI regimen. Fourteen patients were assessable for response: two with complete response (CR), five with partial response (PR), two with stable disease (SD), and five with progressive disease (PD). The objective response rate was 50% (two CR, five PR), and the disease control rate was 64% (two CR, five PR, and two SD). Seven out of 14 patients (50%) were alive at the last follow-up, ranging from 2.6 to 32.4 months. The median progression-free survival and median overall survival were 3.5 months (range 0.5–12 months) and 8 months (range 1–28 months), respectively. Sixteen patients were assessable for toxicity, with the most common grade 3 or 4 adverse events being alopecia (62%), leukopenia (40%), abdominal pain (38%), diarrhea (23%), and mucositis (16%), etc. No fatal adverse events have been observed, and modest adverse effects can be administered.ConclusionIrinotecan and doxorubicin hydrochloride liposome regimens have positive efficacy on relapsed or refractory pediatric WT with well-tolerated toxicity. A prospective clinical trial is warranted.

Multiple blood parameters may serve as a warning to immunochemotherapy-related interstitial lung disease in B-cell lymphoma.

The main aim of this study was to determine some simple but meaningful parameters that indicate immunochemotherapy-related interstitial lung disease (ILD) early in B-cell lymphoma and provide direction to hematologists. The clinical and laboratory characteristics, the treatments and outcomes of 21 B-cell lymphoma patients with ILD who underwent rituximab (RTX) -based immunochemotherapy were collected and retrospectively analyzed. More cycles of immunochemotherapy and higher cumulative doses of RTX and doxorubicin hydrochloride liposome conferred a high risk of ILD. Compared to the baseline, patients had a significantly lower white blood cell count (WBC), absolute lymphocyte count (ALC), and albumin level (4.95×109 vs. 6.32×109, 0.71×109 vs. 1.61×109, 34.1 vs. 40.4 g/L; P<0.05), and higher C-reactive protein (CRP), alpha-hydroxybutyrate dehydrogenase (α-HBDH), and lactate dehydrogenase (LDH) (15.36 vs. 7.00 mg/L, 293.0 vs. 163.1 U/L, 361.8 vs. 231.1 U/L; P<0.05) levels at ILD onset. Further, a positive correlation was found between early glucocorticosteroid intervention and the good prognostication of ILD. In addition, an analysis of the prognoses of 2 cases of patients with pneumocystis pneumonia (PCP) infection indicated that after 3 cycles of treatment, patients, especially unfit patients or those who have received ILD glucocorticoid treatment, may need to receive trimethoprim/sulfamethoxazole (TMP/SMX) to prevent PCP. There was a relationship between variations of blood parameters and the occurrence of ILD which might serve as a warning for B-cell lymphoma patients with immunochemotherapy-related ILD.

Dual targeting single arrow: Neutrophil-targeted sialic acid-modified nanoplatform for treating comorbid tumors and rheumatoid arthritis

Clinically, rheumatoid arthritis (RA) is frequently accompanied by multi-system diseases. Among them, the incidence of comorbid tumors in RA is relatively high, resulting in a gradual increase in mortality; this poses a considerable challenge to clinical treatment. To date, no effective treatment plan for simultaneous tumor and RA therapy is available. Accordingly, we reported a sialic acid-modified doxorubicin hydrochloride liposome (DOX-SAL) that targets peripheral blood neutrophils (PBNs), which play an important role in tumors and RA. Furthermore, the prepared liposome induced PBN apoptosis by binding to L-selectin, which is highly expressed on the surface of PBNs activated by inflammation. This liposome, in turn, reduced the accumulation of inflammatory neutrophils at the disease site. In the first successfully established mouse model of RA comorbidity, induced by employing S180 sarcoma cells and collagen, DOX-SAL effectively inhibited tumor growth while simultaneously alleviating systemic RA symptoms without side effects. Additionally, the animals demonstrated adequate growth during the 48 days of treatment. This treatment strategy encompasses the best of both worlds, breaking the deadlock that tumors and RA cannot be effectively treated in parallel, highlighting a new concept and reference for the clinical treatment of comorbid tumors and RA.

Doxorubicin Hydrochloride Liposome-Based CHOP Regimen in the Initial Treatment of Elderly Patients with Diffuse Large B-Cell Lymphoma: A Retrospective Study

To evaluate the efficacy and safety of CHOP regimen based on doxorubicin hydrochloride liposome in the initial treatment of elderly patients with diffuse large B-cell lymphoma (DLBCL). Thirty-one patients with DLBCL treated from January 1, 2012 to December 31, 2019 were analyzed retrospectively, their median age was 83 (71-95) years old, and all of them were in Ⅲ-Ⅳ stage, including 17 cases who had international prognostic index (IPI) ≥ 3. The patients were treated with R-CHOP and CHOP regimens based on doxorubicin hydrochloride liposome. The efficacy and safety were evaluated during and after treatment. A total of 219 chemotherapy cycles and 7 median cycles were performed in 31 patients. The overall response (OR) rate and complete remission (CR) rate was 80.7% (25/31) and 61.3% (19/31), respectively, as well as 2 cases (6.5%) stable, 4 cases (12.9%) progressive. The main toxicities were as follows: the incidence of grade Ⅲ -Ⅳ neutropenia was 29% (9/31); two patients (6.5%) developed degree Ⅰ-Ⅱ cardiac events, which were characterized by new degree Ⅰ atrioventricular block; there were no cardiac events requiring emergency treatment and discontinuation of chemotherapy. The 1-year, 2-year and 3-year overall survival rate was 83.9%, 77.4% and 61.3%, respectively. The 1-year, 2-year and 3-year progression-free survival rate was 77.4%, 64.5% and 61.3%, respectively. The chemotherapy regimen based on doxorubicin hydrochloride liposome has better efficacy and higher cardiac safety for elderly patients with DLBCL.

The efficacy and safety of irinotecan plus doxorubicin liposome in relapsed/refractory Wilms’ tumors: A retrospective study.

e22007 Background: To evaluate the efficacy of the regimen of combination of irinotecan and doxorubicin hydrochloride liposome in relapsed/refractory pediatric Wilms’ tumor. Life quality and toxicity are seriously considered and assessed. Methods: The project stipulated 5-day course of irinotecan 50 mg/m2 (90-minute infusion) and doxorubicin hydrochloride liposome 40mg/m2 every 3 weeks. Granulocyte colony-stimulating factor was applied when the number of neutrophil count was lower than 1,000/ L. Results: 16 patients received 1to 8 courses (median, 3 courses) of this regimen, including 8 males and 8 females, with a median age of 4.2 years old (range, 0.5-11) . 2 patients were not assessable for response (1were treated in third CR, and 1with refractory WT received only one course as part of complex salvage regimens). Of 14 patients treated for relapsed or refractory Wilms’ tumor and accessed for response, 2 patients had complete responses (CR), 5 patients had partial responses (PR). Of 2 patients had stable diseases (SD), including 1 patient showed objective response on pulmonary lesion. The disease control rate was 64% (2 CR, 5 PR, and 2 SD), and the objective response rate was 50% (2 CR, 5 PR). The median progression-free survival was 3.5 months (range 0.5-12), and the median survival duration was 8 months (range 1-28). Myelosuppressive and gastrointestinal adverse effects were self-limited and clinically controllable with routinely intervention, and this therapeutic regimen was generally continued without delayed therapy. Multiple courses of this regimen had no cumulative toxicity and achieved disease control in relapsed or refractory Wilms’ tumor. Conclusions: The regimen of combination of irinotecan and doxorubicin hydrochloride liposome has positive effect on relapsed/refractory Wilms’ tumor with gentle toxicity without reducing the efficacy, and achieves good quality of life.