Recombinant Human Endostatin Research Articles

P4.11E.07 Envafolimab Combined with Recombinant Human Endostatin and Chemotherapy for NSCLC

P4.11E.07 Envafolimab Combined with Recombinant Human Endostatin and Chemotherapy for NSCLC

P4.11E.06 Envafolimab Combined with Recombinant Human Endostatin and Chemotherapy as First-Line Treatment for Advanced Squamous NSCLC

P4.11E.06 Envafolimab Combined with Recombinant Human Endostatin and Chemotherapy as First-Line Treatment for Advanced Squamous NSCLC

Real-world effectiveness and safety of recombinant human endostatin plus PD-1 inhibitors and chemotherapy as first-line treatment for EGFR/ALK-negative, advanced or metastatic non-small cell lung cancer

BackgroundThis study aimed to evaluate the effectiveness and safety of recombinant human endostatin (Rh-endostatin) plus programmed cell death 1 (PD-1) inhibitors and chemotherapy as first-line treatment for advanced or metastatic non-small cell lung cancer (NSCLC) in a real-world setting.MethodsThis was a retrospective study on patients with EGFR/ALK-negative, advanced or metastatic NSCLC. Patients received Rh-endostatin plus PD-1 inhibitors and chemotherapy every three weeks for 4 to 6 cycles. The primary endpoint was progression-free survival (PFS), and the secondary endpoints were objective response rate (ORR), disease control rate (DCR), overall survival (OS), and safety.ResultsA total of 68 patients were included in this retrospective analysis. As of data cutoff (December 13, 2022), the median follow-up of 21.4 months (interquartile range [IQR], 8.3-44.4 months). The median PFS and OS was 22.0 (95% confidence interval [CI]: 16.6-27.4) and 31.0 months (95% CI: 23.4-not evaluable [NE]), respectively. The ORR was 72.06% (95% CI: 59.85-82.27%), and DCR was 95.59% (95% CI: 87.64-99.08%). Patients with stage IIIB/IIIC NSCLC had significantly longer median PFS (23.4 vs. 13.2 months), longer median OS (not reached vs. 18.0 months), and higher ORR (89.2% vs. 51.6%) than those with stage IV NSCLC (all p ≤ 0.001). The ORR was higher in patients with high PD-L1 expression (tumor proportion score [TPS] ≥ 50%) than in those with low PD-L1 expression or positive PD-L1 expression (75% vs. 50%, p = 0.025). All patients experienced treatment-related adverse events (TRAEs), and ≥ grade 3 TRAEs occurred in 16 (23.53%) patients.ConclusionsRh-endostatin combined with PD-1 inhibitors plus chemotherapy as first-line treatment yielded favorable effectiveness with a manageable profile in patients with advanced or metastatic NSCLC, representing a promising treatment modality.

A single-center, retrospective study-spring-evaluating the efficacy and safety of recombinant human vascular endothelial inhibitor combined with anti-PD-1 in elderly patients aged 80 and above with NSCLC.

To investigate the efficacy and safety of combining Recombinant Human Endostatin Injection (marketed as Endo) with anti-PD-1 in elderly patients aged 80 and above with non-small cell lung cancer (NSCLC). Retrospective analysis of 181 patients with NSCLC aged 80 and above treated in the Department of Respiratory and Critical Care Medicine at Chaohu Hospital, affiliated with Anhui Medical University, from June 2019 to January 2024. Patients who received at least one cycle of combined Endo with anti-PD-1 were included based on inclusion criteria. Clinical and pathological data were collected, including complete blood count, liver and kidney function, electrocardiogram, coagulation function, thyroid function, cardiac enzymes, and whole-body imaging. Adverse events were recorded with a final follow-up on January 25, 2024. The primary endpoints were progression-free survival (PFS) and overall survival (OS), with safety as a secondary endpoint. This study involved 14 elderly patients with NSCLC aged over 80. Median progression-free survival (mPFS) was 102 days, and median overall survival (mOS) was 311 days. Subgroup analyses based on treatment cycles showed a non-significant 441-day mPFS increase in the long-term group (≥6 cycles, 5 patients) compared to the short-term group (<6 cycles, 9 patients). However, the mOS in the long-term group significantly exceeded the short-term group by 141 days, with statistical significance (P=0.048). Further categorization revealed a 204-day shorter mPFS in the monotherapy maintenance group (Endo or Immunol) compared to the combination maintenance group (Endo combined with Immunol, 441 days). The mOS of the monotherapy maintenance group was longer (686 days) than the combination maintenance group (311 days), but no statistical significance (P= 0.710, 0.920). Throughout the treatment, 77 adverse events were recorded, mainly grade 1-2, with no new treatment-related reactions occurred. Overall, the safety of Endo combined with anti-PD-1 was considered good and manageable. The combination of Endo and anti-PD-1 could be an effective treatment choice for patients with NSCLC aged 80 and above.

LGG-10. RECOMBINANT HUMAN ENDOSTATIN IN COMBINATION WITH CHEMOTHERAPY FOR PEDIATRIC LOW-GRADE GLIOMAS

Abstract BACKGROUND Pediatric low-grade gliomas (pLGGs) entail highly effective treatment regimens. In this study, we aimed to examine the efficacy and safety of recombinant human endostatin (rh-ES) combined with chemotherapy for pLGGs. METHODS We collected the clinical data of pLGG patients treated with carboplatin and vincristine (CV) plus rh-ES in the Department of Neuro-oncology, Sanbo Brain Hospital Capital Medical University, Beijing, China, from July 2015 to October 2019 and retrospectively analyzed the effectiveness and safety of this regimen. RESULTS A total of 41 eligible patients were enrolled. Median age at diagnosis was 4 years. Median follow-up lasted for 22.7 months (range 8-73.4 months). Six patients achieved complete response, 7 attained partial response, 4 had minor response, the disease was stable in 3 cases, and in 1 the condition progressed. The objective response rate was 90.2% and complete response rate was 14.6%. The median time to response was 4.1 months. The duration of response was 28.1 months. The progression rate within 6 months of treatment completion was 6.9%. 5-year rates were 74% for progression-free survival and 92% for overall survival. The main toxicities included myelosuppression and carboplatin allergy. No serious rh-ES-related toxicities were observed. CONCLUSIONS Rh-ES in combination with CV in pLGG patients was effective and safe and could achieve rapid and lasting responses.

To investigate the clinical efficacy of recombinant human endostatin combined with FOLFOX4 in the treatment of advanced colorectal cancer.

To investigate the clinical efficacy of recombinant human endostatin combined with FOLFOX4 in the treatment of advanced colorectal cancer.

Toripalimab (anti-PD-1) plus recombinant human endostatin as adjuvant therapy in patients with resected stage III melanoma: Interim analysis of an open-label phase II trial.

e21557 Background: Patients with completely resected stage III melanoma are under high risk of disease recurrence. Recurrence-free survival (RFS) remains unsatisfactory despite there is adjuvant anti-PD-1 monotherapy following surgery, with the 1-year RFS about 70% and 2-year RFS about 49% in our country. It's urgent to explore combined regimens with anti-PD-1 to further improve the RFS. Here we report the interim efficacy and safety results of toripalimab (a PD-1 inhibitor) plus recombinant human endostatin (an angiogenesis inhibitor) as combined adjuvant therapy for patients with resected stage III melanoma. Methods: This prospective single-center, single-arm, open-label phase II trial screened adult patients with stage III melanoma who had undergone complete tumor resection within the previous 13 weeks for eligibility. Toripalimab was administrated in intravenous drip to patients at 3 mg/kg every 2 weeks in a 4-week cycle (day 1 and day 15 of each cycle), for up to 13 cycles or until disease recurrence, unacceptable toxicity or decease. Recombinant human endostatin was administrated in a continuous intravenous infusion at a dose of 210 mg from day 1 to day 3 for each 4-week cycle, for up to 6 cycles or until disease recurrence, unacceptable toxicity or decease. The primary endpoints were the 1-year and 2-year RFS. Results: By the data cut-off on Jan 25, 2024, 43 eligible patients with resected stage III melanoma between October 2021 and December 2023 were enrolled. In ITT population (n = 43), patients' median age was 56 (IQR 52~69) years. There were 25 (58%) male and 18 (42%) female; 27 (63%) with acral melanoma and 16 (37%) with cutaneous melanoma. With a median follow-up of 14 months, the 1-year and 2-year RFS rates were 83% and 71%, respectively. For security, 33 (77%) patients experienced at least one adverse event (AE), including 27 grade 1-2 AEs and 6 grade 3~4 AEs. One patient discontinued the combined therapy due to immunotherapy-associated myocarditis. Conclusions: Toripalimab in combination with recombinant human endostatin as adjuvant therapy could further improve disease-free survival in Chinese patients with completely resected stage III melanoma, with a manageable toxicity profile. Clinical trial information: 05907512 .

Real-world effectiveness and safety of PD-1 inhibitors combined with recombinant human endostatin and chemotherapy in refractory, recurrent/metastatic nasopharyngeal carcinoma.

e18007 Background: Nasopharyngeal carcinoma(NPC) is one of the most common head and neck malignancies with a high overall survival rate. However, the treatment of refractory, recurrent or metastatic NPC is complicated. This study aimed to evaluate the safety and effectiveness of GEP (Gemcitabine combined with recombinant human endostatin (Rh-endostatin) and anti-PD-1 antibody) in patients with refractory, recurrent or metastatic NPC that cannot be treated locally in the real-world setting. Methods: Patients with refractory, recurrent or metastatic NPC (Refractory patients were defined as those unsuitable for local treatment due to extensive tumor recurrence/metastasis or necrosis of ulcers) treated in our hospital from December 2022 to October 2023 were retrospectively reviewed and analyzed. with the GEP regimen. Patients received 1-6 cycles of GEP therapy, including Gemcitabine (1.0 g /m2 ond1 and d8) combined with Rh-endostatin (180-210 mg/continuous intravenous pump 72-120h) and PD-1 antibody, Objective response rate (ORR) and disease control rate (DCR) were determined by Clopper-Pearson's method. The incidence of adverse events (AES). Results: A total of 25 patients who completed ≥ 2 cycles of treatment and at least one efficacy assessment were included in the efficacy analysis. The median age was 59 years (range: 33-75 years), 36% of patients ≥ 65 years. There was significant liquefaction necrosis in 17 cases (68%). 68% of the patients were treated with second-line or above GEP. 32% (8/25) of patients had tumor progression after anti-vascular therapy, and 44% (11/25) had disease progression after immunotherapy. Based on RECIST 1.1, the ORR was 44.00% (95%CI: 26.67%, 62.93%), and DCR was 92.00% (95%CI: 70.04%, 95.83%). The history of immunotherapy was a significant influence factor on ORR. 30 patients who received at least one course of GEP therapy were included in the safety analysis. Grade 3 AEs were observed in 7 patients (20%), with hematological toxicity (6/7) and hypertension (1/7). Other AEs with more than 20% incidence were hematological toxicity (93.0%), weight loss (67.0%), abdominal distension and constipation (47.0%), hypertension (47%), infection (33.0%), liver dysfunction (27.0%), nausea and vomiting (23.0%), and infusion reaction (20.0%). The recurrent lesions of 15 patients with recurrent NPC were accompanied by significant liquefaction necrosis and ulcers. The ORR was 46.7%, and DCR was 100%. Among them, 5 patients had grade 1 nosebleed, and the other grade 2 or above AEs were hematological toxicity, and there were no grade 4 treatment-related AEs. Conclusions: Real-world data demonstrated that GEP was well-tolerated, safe and effective in patients with refractory, recurrent or metastatic NPC.

Immunotherapy combined with antiangiogenic therapy as third- or further-line therapy for stage IV non-small cell lung cancer patients with ECOG performance status 2: A retrospective study.

Patients with Eastern Cooperative Oncology Group performance status (ECOG PS) 2 probably cannot tolerate chemotherapy or other antitumor therapies. Some studies have reported that immunotherapy combined with antiangiogenic therapy is well-tolerated and shows good antitumor activity. However, the efficacy of this combination as a later-line therapy in patients with ECOG PS 2 is unclear. This study evaluated the effectiveness and safety of this combination strategy as third- or further-line therapy in stage IV non-small cell lung cancer (NSCLC) patients with ECOG PS 2. In this retrospective study, patients treated with camrelizumab plus antiangiogenic therapy (bevacizumab, anlotinib, or recombinant human endostatin) were included. Objective response rate (ORR), disease control rate (DCR), progression-free survival (PFS), overall survival (OS), quality of life (QOL) assessed by ECOG PS, and safety were analyzed. Between January 10, 2019, and February 28, 2024, a total of 59 patients were included. The ORR was 35.6% (21/59) and the DCR was 86.4%. With a median follow-up of 10.5 months (range: 0.7-23.7), the median PFS was 5.5 months (95% confidence interval [CI]: 3.8-7.3) and the median OS was 10.5 months (95% CI: 11.2-13.6). QOL was improved (≥1 reduction in ECOG PS) in 39 patients (66.1%). The most common Grade 3-4 treatment-related adverse events were hepatic dysfunction (6 [10%]), hypertension (5 [8%]), and hypothyroidism (3 [5%]). There were no treatment-related deaths. Third- or further-line immunotherapy combined with antiangiogenic therapy is well-tolerated and shows good antitumor activity in stage IV NSCLC patients with ECOG PS 2. Future large-scale prospective studies are required to confirm the clinical benefits of this combination therapy.

Induction chemotherapy followed by concurrent chemoradiotherapy combined with toripalimab and Endostar in high-risk locally advanced nasopharyngeal carcinoma: A multicenter, randomized, phase 2 trial.

6086 Background: Even though induction chemotherapy (IC) followed by concurrent chemoradiotherapy (CCRT) can improve the survival rate of patients with locally advanced nasopharyngeal carcinoma (LA-NPC), the recurrence and/or metastasis rates for patients with stage IV (T4 and/or N3) diseases remain high. This study investigates the efficacy and safety of adding Toripalimab (PD-1 inhibitor) and Endostar (recombinant human endostatin) to IC-CCRT in patients with high-risk LA-NPC. Methods: High-risk LA-NPC patients were randomly divided (1:1) into either the IC-CCRT+TE group (gemcitabine and cisplatin induction chemotherapy followed by concurrent chemoradiotherapy combined with Toripalimab and Endostar) or the IC-CCRT group (gemcitabine and cisplatin induction chemotherapy followed by concurrent chemoradiotherapy). Toripalimab (240mg, d1) was administered intravenously every 3 weeks for up to 12 cycles (3 induction, 2 concurrent, and 7 adjuvant). Endostar (7.5mg/m2, d1-10) was continuously injected intravenously every 3 weeks for a total of 5 cycles (3 induction and 2 concurrent). The primary endpoint was 3-year progression-free survival (PFS), and the secondary endpoints included 3-year overall survival (OS), 3-year locoregional relapse-free survival (LRFS), 3-year distant metastasis-free survival (DMFS), objective response rate (ORR) and safety. Results: From September 7, 2020, to August 23, 2022, a total of 106 eligible patients were randomly assigned to the IC-CCRT+TE group (n = 53) and IC-CCRT group (n = 53). At a median follow-up of 25 months, the PFS was significantly improved in the IC-CCRT+TE group compared to the IC-CCRT group (HR=0.36, p=0.041). 28 patients (52.8%) in the IC-CCRT+TE group and 5 patients (9.4%) in the IC-CCRT group achieved complete response (CR) after induction chemotherapy, and the difference was statistically significant (P &lt; 0.001). The incidence of grade ≥3 acute adverse events in the IC-CCRT+TE group and IC-CCRT group was 66.0% and 62.3%, respectively. The incidence of grade ≥3 late adverse events in two groups was 5.8% and 5.7%, respectively. The incidence of grade ≥3 immune-related adverse events was only 4.7%. Conclusions: IC-CCRT combined with Toripalimab and Endostar significantly improved PFS in patients with high-risk locally advanced nasopharyngeal carcinoma, and the adverse events are manageable. Clinical trial information: NCT04447326 .

A meta-analysis of recombinant human endostatin combined with NP regimen for treating non-small cell lung cancer.

The aim of this study was to evaluate the efficacy and safety of recombinant human endostatin in combination with vinorelbine + cisplatin (NPE) for the treatment of advanced non-small cell lung cancer (NSCLC). Randomized controlled trials (RCTs) of NPE for advanced NSCLC in PubMed, Cochrane Library, EMBASE, Web of Science, China National Knowledge Infrastructure, and Wanfang databases were searched using a computerized search of the database from the time of creation to May 2023. Two investigators independently extracted literature information and assessed the quality of the included literature. Meta-analysis was performed using RevMan 5.4.0 software. A total of 24 RCTs with 2114 patients with advanced NSCLC were finally included. The results of meta-analysis showed that the total effective rate in the group received NPE regimen was significantly higher than those in the group without NPE regimen (RR = 1.70, 95% CI: 1.48-1.95, P < .00001). Meanwhile, the clinical benefit rate in the group received NPE regimen was also significantly higher than those in the group without NPE regimen (RR = 1.22, 95% CI: 1.15-1.29, P < .00001). However, there was no significant difference in the incidence of adverse event rate between the 2 groups (RR = 0.98, 95% CI: 0.76-1.27, P = .88). Compared with NP (vinorelbine + cisplatin) regimens for patients with advanced NSCLC, NPE regimens improve the total effective rate and clinical benefit rate of treatment, but there can be no significant difference in adverse effects. Prospective randomized trials are needed to further validate the safety and efficacy of this treatment modality.

The efficacy and safety of continuous intravenous infusion of rh-endostatin combined with platinum-based doublet chemotherapy for advanced non-small-cell lung cancer

BackgroundPlatinum-based doublet chemotherapy is commonly used in the treatment of non-small cell lung cancer (NSCLC). A growing body of evidence indicates that incorporating antiangiogenic agents into platinum-based chemotherapy may enhance the survival outcomes for NSCLC patients. However, the optimal administration protocol for intravenous recombinant human endostatin (rh-endostatin), an antiangiogenic agent, remains uncertain at present.AimThis study aims to investigate the efficacy and safety of 5-d continuous intravenous infusion of rh-endostatin in combination with chemotherapy for patients with advanced NSCLC. The predictive biomarkers for this treatment regimen were further probed.MethodsThis prospective, single-arm multicenter study enrolled a total of 48 patients with advanced NSCLC who were histologically or cytologically confirmed but had not received any prior treatment from January 2021 to December 2022. Prior to the chemotherapy, these patients received a continuous intravenous infusion of rh-endostatin (210 mg) over a period of 120 h, using an infusion pump. The chemotherapy regimen included a combination of platinum with either pemetrexed or paclitaxel, given in 21-day cycles. The primary endpoint of the study was median progression-free survival (mPFS), and the secondary endpoints included median overall survival (mOS), objective response rate (ORR), disease control rate (DCR), and assessment of adverse events (AEs).ResultsThe mPFS was 6.5 months (95% confidence interval (CI): 3.8–9.1 m) while the mOS was 12.3 months (95% CI: 7.6–18.5 m). The ORR and DCR was 52.1% and 75.0%, respectively. Leukopenia (52.1%), anemia (33.3%), and thrombocytopenia (20.8%) were the most common adverse effects and these toxicities were deemed acceptable and manageable. In addition, a correlation was noted between elevated serum carcinoembryonic antigen (CEA) levels and decreased PFS and OS.ConclusionsThe incorporation of a 5-day continuous intravenous infusion of rh-endostatin into platinum-based doublet chemotherapy has demonstrated both safety and efficacy in the treatment of advanced NSCLC. Furthermore, the baseline serum levels of CEA may potentially function as a predictor for the efficacy of rh-endostatin when combined with chemotherapy in NSCLC patients.ClinicalTrials.govNCT05574998.

The Preventive Effect of Endostar on Radiation-induced Pulmonary Fibrosis.

Radiation-induced pulmonary fibrosis (RIPF) is a long-term complication of thoracic radiotherapy without effective treatment available. This study aimed to establish a RIPF mouse model and explore the therapeutic effects and mechanisms of recombinant human endostatin (Endostar). C57BL/6 mice received a 16-Gy dose of X-rays to the whole thorax with or without the administration of Endostar for 24 weeks. Radiation-induced body weight loss was partially attenuated by Endostar (P<0.05). Endostar significantly reduced alveolar inflammation (P<0.05) and pulmonary fibrosis (P<0.001), as indicated by a decrease in the expression levels of collagen I and collagen IV in lung tissue (both P<0.001). Angiogenesis (as shown by CD31 immunohistochemistry) was also decreased (P<0.01). In irradiated mice, Endostar inhibited the transforming growth factor-β1 (TGF-β1)/drosophila mothers against the decapentaplegic 3 (Smad3)/extracellular regulated protein kinases (ERK) signaling pathway (all P<0.05). In vitro, Endostar treatment decreased the radiation-induced expression of TGF-β1, vascular endothelial growth factor (VEGF), p-Smad3, and p-ERK in alveolar epithelial cells and vascular endothelial cells (all P<0.05). Endostar could alleviate RIPF through decreased antiangiogenic activity and inhibition of the TGF-β1/Smad3/ERK pathway.

Generation and utilization of endostatin-sensitive cell lines for assessing the biological activity of endostatin.

Recombinant proteins are gaining increasing popularity for treating human diseases. The clinical effectiveness of recombinant proteins is directly related to their biological activity, which is an important indicator in drug development and quality control. However, certain recombinant proteins have unclear or complex signal pathways, making detecting their activity in vitro difficult. For instance, recombinant human endostatin (endostatin), a new antitumor drug developed in China, lacks a sensitive and stable assay for its biological activity since being market approval. To address this issue, we performed a genome-wide screening of immortalized human umbilical vein endothelial cells (HUVECs) using a CRISPR/Cas9 knockout library containing 20,000 targeted genes. We identified two potential endostatin-resistant genes, NEPSPP and UTS2, and successfully constructed a highly sensitive cell line, HUVEC-UTS2-3#, by knocking down the UTS2 gene. Based on the optimized parameters of HUVEC-UTS2-3# cells, we established a new method for detecting the biological activity of endostatin. The method was validated, and it produced results consistent with primary HUVEC cells but with higher sensitivity and more stable data. The use of gene-editing technology provides a novel solution for detecting the biological activity of recombinant proteins that other methods cannot detect.

Pre-clinical Efficacy and Safety Pharmacology of PEGylated Recombinant Human Endostatin.

This study aimed to outline the pre-clinical efficacy and safety pharmacology of PEGylated recombinant human endostatin (M2ES) according to the requirements of new drug application. The purity of M2ES was evaluated by using silver staining. Transwell migration assay was applied to detect the bioactivity of M2ES in vitro. The antitumor efficacy of M2ES was evaluated in an athymic nude mouse xenograft model of pancreatic cancer (Panc-1) and gastric cancer (MNK45). BALB/C mice were treated with different doses of M2ES (6, 12 and 24 mg/kg) intravenously, both autonomic activity and cooperative sleep were monitored before and after drug administration. The apparent molecular weight of M2ES was about 50 kDa, and the purity was greater than 98%. Compared with the control group, M2ES significantly inhibits human micro-vascular endothelial cells (HMECs) migration in vitro. Notably, weekly administration of M2ES showed a significant antitumor efficacy when compared with the control group. Treatment of M2ES (24mg/kg or below) showed no obvious effect on both autonomic activity and hypnosis. On the basis of the pre-clinical efficacy and safety pharmacology data of M2ES, M2ES can be authorized to carry out further clinical studies.

Efficacy and Safety Analysis of Recombinant Human Endostatin (Endostar) Combined With Chemoradiotherapy for Locally Advanced Cervical Cancer: A 2-Center Retrospective Study.

This study aims to assess the efficacy and safety of Endostar in the management of locally advanced cervical cancer. This retrospective, 2-center study enrolled 41 patients with locally advanced cervical cancer between June 2017 and December 2020. The patients were subjected to a combination of Endostar and chemoradiotherapy until they experienced disease progression or an unacceptable level of toxicity. The patients in the Endostar combined chemoradiotherapy (E + CRT) and CRT groups were matched 1:1 based on clinical features, including age, disease stage, and pathological type. The therapeutic efficacy and safety outcomes were compared between the 2 groups. Early treatment response: the CR rates in E + CRT and CRT groups were 48.8% and 26.8%, respectively (χ2 = 4.20, P < .05). The ORR and DCR were not significantly different between the 2 groups. Long-term efficacy: there was no significant difference in the 1-year and 2-year PFS rates and OS rates between 2 groups. However, in patients with stage IIB, subgroup analyses revealed a significant difference in PFS between the 2 groups (P < .05). Prognostic factors: stage, Eastern Cooperative Oncology Group (ECOG) score, and tumor size were independent predictive factors for PFS, while ECOG score and tumor size were those of OS in patients with locally advanced cervical cancer. Safety: The incidence of grade III-IV myelosuppression was significantly lower in E + CRT group than in CRT group (P < .05). The combination of Endostar and concurrent CRT exhibited greater efficacy in treating locally advanced cervical cancer with no severe adverse reactions, when compared to simple CRT. It is expected that this approach will evolve into a new treatment alternative for patients with locally advanced cervical cancer.

Enhancing safety and therapeutic efficacy: PD-1 inhibitor and recombinant human endostatin combination in advanced non-small cell lung cancer patients.

To assess the therapeutic efficacy of combining a programmed death-1 (PD-1) inhibitor with recombinant human endostatin in patients diagnosed with advanced non-small cell lung cancer (NSCLC). We retrospectively collected data from 83 patients with advanced NSCLC who received treatment at Xi'an Daxing Hospital between May 2020 and July 2022. Among them, 42 patients were treated with a PD-1 inhibitor combined with recombinant human endostatin (observation group), while 41 patients received PD-1 inhibitor monotherapy (control group). We evaluated the objective response rate, changes in serum tumor markers pre- and post-treatment, occurrence of adverse reactions, progression-free survival (PFS), 1-year survival rate, and identified independent risk factors affecting prognosis in both groups. The treatment efficacy in the observation group significantly surpassed that in the control group. Following treatment, the levels of cytokeratin 19 fragment antigen 21-1, carcinoembryonic antigen, and carbohydrate antigen 125 decreased significantly in the observation group compared to the control group (P < 0.001). There was no notable difference in the incidence of adverse reactions between the two groups (P < 0.001). The median PFS and 1-year survival rate were notably higher in the observation group (P < 0.001). Age, liver metastasis, and treatment regimen emerged as independent risk factors affecting poor prognosis in patients (P < 0.001). Combining a PD-1 inhibitor with recombinant human endostatin in patients with advanced NSCLC not only enhances clinical efficacy but also increases PFS and the 1-year survival rate while ensuring treatment safety. This combination therapy shows promise for clinical application.

Recombinant human endostatin as a potential anti-angiogenic agent: therapeutic perspective and current status.

Angiogenesis is the physiological process that results in the formation of new blood vessels develop from pre-existing vasculature and plays a significant role in several physiological and pathological processes. Inhibiting angiogenesis, a crucial mechanism in the growth and metastasis of cancer, has been proposed as a potential anticancer therapy. Different studies showed the beneficial effects of angiogenesis inhibitors either in patients suffering from different cancers, alone or in combination with conventional therapies. Even though there are currently a number of efficient anti-angiogenic drugs, including monoclonal antibodies and kinase inhibitors, the associated toxicity profile and theiraffordability constraints are prompting researchers to search for a safe and affordable angiostatic agent for cancer treatment. Endostatin is one of the endogenous anti-angiogenic candidates that have been extensively pursued for the treatment of cancer, but even over three decades after its discovery, we have not made much advancement in employing it as an anticancer therapeutic despite of its remarkable anti-angiogenic effect with low toxicity profile. A recombinant human endostatin (rh-Es) variant for non-small cell lung cancer was approved by China in 2006 and has since been used effectively. Several other successful clinical trials related to endostatin for various malignancies are either ongoing or have already been completed with promising results. Thus, in this review, we have provided an overview of existing anti-angiogenic drugs developed for cancer therapy, with a summary of tumour angiogenesis in the context of Endostatin, and clinical status of rh-Es in cancer treatment. Furthermore, we briefly discuss the various strategies to improve endostatin features (poor pharmacokinetic properties) for developing rh-Es as a safe and effective agent for cancer treatment.

Chinese expert consensus on treatment of malignant pleural effusion (2023 Edition)

Malignant pleural effusion (MPE) is a pleural effusion that is caused by a malignant tumor originating in the pleura or by a metastatic malignant tumor from another site that has invaded the pleura. MPE is associated with poor prognosis. Members of the Pleural and Mediastinal Diseases Working Group (preparatory) of Chinese Thoracic Society and some external experts selected clinical issues related to the management of MPE and conducted rigorous evidence retrieval and evaluation. After several meetings and revisions of the manuscript, recommendations were made. This consensus applies to patients aged≥18 years old with MPE caused by various malignancies except for pleural mesothelioma. It included four chapters: pathogenesis of MPE, prognostic evaluation of MPE, local thoracic treatment, and systemic anticancer therapy for MPE.The main recommendations of this consensus are as follows:1. Prognosis evaluation of MPE was valuable in formulating treatment options. It is suggested to comprehensively evaluate the patient's prognosis by combining the patient's performance status, tumor type, and laboratory examination.2. It is recommended that in patients with symptomatic MPE, therapeutic thoracentesis could be used as the initial therapeutic option. Evaluate whether the lung is expandable after thoracentesis and drainage, and then develop a therapeutic regimen.3. In patients with MPE and known expandable or nonexpandable lung, an indwelling pleural catheter (IPC) is recommended as a first-line pleural management. Daily IPC drainages are recommended. In patients with MPE and expandable lung, talc pleurodesis by talc poudrage or talc slurry is recommended if the drug is accessible. Other pleurodesis agents include povidone iodine, bleomycin, and doxycycline.4. After drainage, it is suggested to consider the option of intrapleural use of recombinant human endostatin or bevacizumab alone or in combination with intrapleural chemotherapy. Intrapleural intervention including electrocautery, argon knife, cryotherapy, laser and radiofrequency ablation, is recommended for use in patients who have undergone rigorous evaluation in eligible hospitals. The use of intrapleural urokinase or streptokinase via pleural catheter is recommended for patients with symptomatic MPE and loculated effusion.5. For patients with good performance status and metastatic malignancies, systemic anti-cancer treatment is recommended as standard of care.

Efficacy and safety of immune checkpoint inhibitors plus recombinant human endostatin therapy as second-line treatment in advanced non-small-cell lung cancer with negative driver gene: a pilot study.

Immune checkpoint inhibitors (ICIs) have become the standard second-line treatment for advanced non-small cell lung cancer (NSCLC). Recentfindings indicating an intertwined regulation of vascular endothelial growth factor (VEGF) signaling and immunosuppression in the tumor microenvironment suggest that the combination of ICIs and angiogenesis inhibitors could have synergistic antitumor activity, along with favorable tolerability. However, ICIs plus anti-angiogenesis therapy has not been widely evaluated. The purpose of this pilot study was to evaluate the efficacy and safety of ICIs plus recombinant human (rh)-endostatin as second-line treatment in advanced NSCLC with negative driver gene. Prospectively evaluated the efficacy and safety of ICIs plus rh-endostain as second-line treatment in advanced NSCLC with negative driver gene. The primary endpoints of the study were progression-free survival (PFS) and overall survival (OS). The secondary endpoints were objective response rate (ORR), disease control rate (ORR), and safety. A total of 34 patients were recruited in this study. 18 patients received ICIs plus anti-angiogenesis therapy (ICIs combination therapy), and 16 patients received ICIs monotherapy. DCR was 88.9% vs 43.8% (P = 0.009). Median PFS (mPFS) was 8.3 months vs. 3.7 months (HR = 0.276, 95% CI 0.125-0.607, P = 0.001). Median OS (mOS) was 18.0 months vs 9.6 months (HR=0.364, 95% CI 0.147-0.902, P=0.009). In multivariate Cox regression analysis, ICI combination therapy prolonged PFS (HR = 0.069, 95% CI 0.019-0.185, P < 0.001) and OS (HR = 0.044, 95% CI 0.011-0.185, P < 0.001). We did not observe a significant difference in the incidence of adverse events (AEs) between the two groups (P > 0.05). Compared with ICIs monotherapy, ICIs combination therapy improves clinical response in patients with advanced NSCLC with negative driver gene, significantly prolongs PFS and OS, and does not significantly difference the incidence of AEs.