Treatment Of Advanced Malignant Tumors Research Articles

A pharmacovigilance study of adverse event profiles and haemorrhagic safety of bevacizumab based on the FAERS database

ABSTRACT Background Bevacizumab is used for the treatment of advanced malignant tumors; it acts by inhibiting angiogenesis. This study aimed to examine adverse events (AEs) of bevacizumab, especially hemorrhage, using the Food and Drug Administration Adverse Event Reporting System (FAERS) database. Research Design and Methods The reporting odds ratio (ROR) and proportional reporting ratio (PRR) were used to analyze the AEs of bevacizumab using FAERS registration data from January 2004 to September 2022. Clinical information regarding hemorrhagic signals was further analyzed. Results The number of bevacizumab-associated AE reports was 96,477. Our study found that 892 significant preferred terms (PTs) were spread throughout 25 organ systems. The system organ classes (SOCs) focus on general disorders, administration site conditions, blood and lymphatic system disorders, injury, poisoning, and procedural complications. A total of 2,847 bevacizumab-related hemorrhage cases were reported, and 37 hemorrhagic signals were identified. Hemorrhagic signals were focused on SOC levels in vascular, gastrointestinal, and nervous system disorders. Colorectal, lung, and breast cancers are the three most common malignancies associated with BV-induced hemorrhage. Conclusion The AE report from the present study confirms the majority of label information for bevacizumab, while also identifying new AEs. In addition, this was a large descriptive study of bevacizumab-induced hemorrhage.

Real-World Study: A Powerful Tool for Malignant Tumor Research in General Surgery.

Real-world study (RWS) is a method to draw conclusions by collecting and analyzing real-world data under a real clinical background. Compared with traditional randomized controlled trials (RCTs), RWSs are favored by clinicians because of their low cost and good extrapolation. In recent years, RWS has made remarkable achievements in the field of general surgery, especially in the drug treatment of advanced malignant tumors. Therefore, to further understand the main contents of the existing RWS and the application prospect of RWS in the future, this paper systematically reviews the clinical application of RWS in malignant tumors in general surgery in the past three years.

A Therapeutic Whole-Tumor-Cell Vaccine Covalently Conjugated with a TLR7 Agonist.

A single-protein or -peptide vaccine is not sufficient to arouse immune responses in cancer therapy. A whole-tumor-cell vaccine with complete cancer cell antigens and all conformations elicits robust immune responses and is a promising method for the treatment of advanced malignant tumors. In this study, we used 5-azacitidine to stimulate B16-F10 melanoma cells to express toll-like receptor (TLR) 3 on the cell surface and then chemically linked SZU-106, a small-molecule TLR7 agonist, to the cell surface with a pegylated linker to produce a novel whole-tumor-cell vaccine, abbreviated as Aza-BFcell-106. The vaccine stimulated mouse splenic lymphocytes and bone marrow-derived dendritic cells to secrete cytokines, promoted the maturation of dendritic cells and enhanced the capability of dendritic cells to present antigens. In a mouse model of melanoma, the vaccine effectively inhibited tumor growth, decreased tumor volume and prolonged survival. Further combination of the vaccine with a chemokine inhibitor, reparixin, significantly increased the infiltration of CD4+ and CD8+ T cells into the tumor environment, while the antitumor effect was significantly enhanced. The whole-tumor-cell vaccine Aza-BFcell-106 induced immune-activating responses in both in vitro and in vivo experiments, indicating that this vaccine has great potential to treat advanced malignant tumors.

Triggering Immune System With Nanomaterials for Cancer Immunotherapy.

Cancer is a major cause of incidence rate and mortality worldwide. In recent years, cancer immunotherapy has made great progress in the preclinical and clinical treatment of advanced malignant tumors. However, cancer patients will have transient cancer suppression reaction and serious immune related adverse reactions when receiving immunotherapy. In recent years, nanoparticle-based immunotherapy, which can accurately deliver immunogens, activate antigen presenting cells (APCs) and effector cells, provides a new insight to solve the above problems. In this review, we discuss the research progress of nanomaterials in immunotherapy including nanoparticle-based delivery systems, nanoparticle-based photothermal and photodynamic immunotherapy, nanovaccines, nanoparticle-based T cell cancer immunotherapy and nanoparticle-based bacteria cancer immunotherapy. We also put forward the current challenges and prospects of immunomodulatory therapy.

Safety and efficacy of sintilimab combination therapy for the treatment of 48 patients with advanced malignant tumors.

BackgroundSintilimab is a recombinant fully human anti-programmed death 1 (PD-1) monoclonal antibody that blocks the interaction of PD-1 with its ligand. We evaluated the safety and efficacy of sintilimab combined with chemotherapy and targeted therapy in the treatment of advanced malignant tumors.MethodsWe performed a retrospective analysis of the clinical data of patients with advanced malignant tumors treated with sintilimab combined with chemotherapy and targeted therapy admitted to the Third Ward of the Department of Medical Oncology, First Affiliated Hospital of Anhui Medical University, China, from July 2019 to February 2021. The objective response rate (ORR), disease control rate (DCR), progression-free survival (PFS), overall survival (OS) and related adverse reactions were analyzed.ResultsA total of 48 patients with advanced malignant tumors treated with sintilimab combined with chemotherapy and targeted therapy. All 48 patients completed 2 courses of treatment, and the ORR and DCR were 20.83% and 81.25%. The median PFS for all patients in this study was 7 months, and the median OS was not yet reached. The median PFS for the first-line and second-line patients was 10 months, and the median OS was not yet reached. The median PFS for third-line and beyond patients was 7 months, and the median OS was 10 months. The differences in PFS and OS were both statistically significant. Adverse events occurred in 24 patients, of which 18 patients had grade I-II adverse events and 6 patients had grade III-IV adverse events.ConclusionsSintilimab is an inexpensive PD-1 drug produced in China. Sintilimab combination therapy showed good safety in the treatment of advanced malignant tumors, with increases in the treatment efficacy and DCR for advanced tumors. Because of few adverse reactions and proven efficacy, sintilimab combination therapy can be used as an option for the treatment of advanced malignant tumors.

Mechanism underlying the immune checkpoint inhibitor-induced hyper-progressive state of cancer.

Immune checkpoint inhibitors (ICIs) are gradually replacing chemotherapy as the cornerstone of the treatment of advanced malignant tumors because of their long-lasting and significant effect in different tumor types and greatly prolonging the survival time of patients. However, not all patients can respond to ICIs, and even rapid tumor growth after treatment with ICI has been observed in a number of clinical studies. This rapid progression phenomenon is called hyper-progressive disease (HPD). The occurrence of HPD is not uncommon. Past statistics show that the incidence of HPD is 4%-29% in different tumor types, and the progression-free survival and overall survival of patients with HPD are significantly shorter than those of the non-HPD progressor group. With the deepening of the study of HPD, we have established a preliminary understanding of HPD, but the diagnostic criteria of HPD are still not unified, and the addition of biomarkers may break this dilemma. In addition, quite a few immune cells have been found to be involved in the occurrence and development of HPD in the tumor microenvironment, indicating that the molecular mechanism of HPD may be triggered by a variety of ongoing events at the same time. In this review, we summarize past findings, including case reports, clinical trials, and fundamental research; compare the diagnostic criteria, incidence, and clinical prognostic indicators of HPD in different studies; and explore the molecular mechanism and future research direction of HPD.

Observe the Short-term Efficacy and Side Effects of Local Hyperthermia Combined with Chemotherapy in the Treatment of Advanced Malignant Tumors

Observe the Short-term Efficacy and Side Effects of Local Hyperthermia Combined with Chemotherapy in the Treatment of Advanced Malignant Tumors

Efficacy and safety of albumin-bound paclitaxel in the treatment of advanced malignant tumors

Objective To investigate the efficacy and safety of albumin-bound paclitaxel in the treatment of advanced malignant tumors. Methods Patients in advanced stage of cancer who had had drug-resistant relapse after receiving multiple-line treatment received chemotherapy with albumin-bound paclitaxel from May 2016 to April 2018 in Daxing Hospital of Capital Medical University. Their clinical data were collected to evaluate the treatment efficacy and safety profile. Results 36 patients who had advanced treatment-resistent tumors with evaluable data were enrolled. Of 36 patients, 55.56% (20) had previously received chemotherapy with paclitaxel. The objective response rate (ORR) was 8.33%, the disease control rate (DCR) was 25.0%, the median progression free survival (PFS) was 106 days, and the median overall survival (OS) was 183 days. The main adverse reactions of grade 3-4 were hematological toxicity, including neutropenia [36.11% (13/36)], anemia and thrombocytopenia [5.56% (2/36) and 16.67% (6/36)] in patients without neutropenia fever. Adverse effects of 3-4 degrees related to non-hematologic toxicity were not observed. Conclusions Chemotherapy regimen with albumin-bound paclitaxel has certain efficacy for advanced malignant tumors resistant to multiple lines of therapy and the adverse effects could be generally tolerated. Key words: Albumin-bound paclitaxel; Antineoplastic combined chemotherapy protocols; Drug resistance, neoplasm

Preliminary study of efficacy and safety of Pembrolizumab and Nivolumab in treatment of advanced malignant tumors

Objective To preliminarily compare the efficacy and safety of Pembrolizumab and Nivolumab in the treatment of advanced malignant tumors. Methods Clinical data of 50 patients diagnosed with advanced malignant tumors treated with Pembrolizumab and Nivolumab from January 2017 to August 2018 in our hospital were retrospectively analyzed. All patients were divided into the Pembrolizumab (n=26) and Nivolumab groups (n=24). The incidence of adverse reactions was statistically compared between two groups by using χ2 test. The survival analysis was performed by using Kaplan-Meier method. Results The median progression-free survival in the Pembrolizumab group was 213 d, and 146 d in the Nivolumab group (P>0.05). The incidence of aminotransferase elevation and hypothyroidism in the Nivolumab group was significantly higher than that in the Pembrolizumab group (63% vs. 23%, 12% vs. 0%, both P 0.05). Conclusion Clinical efficacy does not significantly differ, whereas the incidence of adverse reactions slightly differs between the Pembrolizumab and Nivolumab groups. Key words: Malignant neoplasm/Immunotherapy; Treatment outcome; Adverse reaction

Safety and efficacy analysis of low-dose apatinib in treatment of advanced malignant tumors

Objective To investigate the safety and efficacy of low-dose apatinib in treatment of advanced malignant tumors. Methods The clinical data of 54 patients with advanced malignant tumors who were admitted to Shanxi Dayi Hospital from March 2015 to March 2018 were analyzed retrospectively. These patients were treated with apatinib at doses of 250 mg (29 cases) and 500 mg (25 cases) after initial treatment or failure of multi-line treatment. There were 15 cases of gastric cancer, 11 cases of lung cancer, 9 cases of ovarian cancer, 7 cases of liver cancer, 6 cases of soft tissue sarcoma, 3 cases of esophageal cancer, 2 cases of melanoma, and 1 case of peritoneal cancer. The objective response rate (ORR), disease control rate (DCR), progress free survival (PFS) and overall survival (OS) were analyzed, and the efficacy and related adverse reactions were evaluated. Results The adverse reactions of 54 patients could be evaluated. Non-hematological drug-related adverse reactions were most common with hypertension, hand-foot skin reaction and proteinuria, while hematologic drug-related adverse reactions were most common with leukopenia and thrombocytopenia. All patients were well tolerated. The incidence of drug-related adverse reactions in the 250 mg dose group was lower than that in the 500 mg dose group, and the incidence of grade Ⅰ-Ⅱ hypertension between the two groups was statistically different (χ 2=6.268, P=0.012). Short-term efficacy: ORR of the patients in the 250 mg and 500 mg dose groups was 6.9% (2/29) and 12.0% (3/25), respectively; DCR was 41.4% (12/29) and 52.0% (13/25), respectively; and the 500 mg dose group was superior to the 250 mg dose group, but the differences were not statistically significant (ORR: χ2=0.416, P=0.519; DCR: χ2=0.609, P=0.435). Long-term efficacy: the 500 mg dose group had a slight advantage over the 250 mg dose group in both median PFS time (3.9 months vs. 3.6 months) and median OS time (7.8 months vs. 7.6 months), but the differences were not statistically significant (PFS: χ2=0.472, P=0.492; OS: χ2=0.261, P=0.609). Conclusions Low-dose apatinib can be used to treat advanced malignant tumors. The drug-related adverse reactions are small, the curative effects are exact, the adverse reactions are easy to tolerate, and it is convenient for long-term use. Low-dose apatinib is one of the treatment options for advanced malignant tumors. Key words: Malignant tumors; Apatinib; Low-dose; Adverse reactions

Analysis of clinical efficacy and prognostic factors of apatinib in the treatment of advanced malignant tumors

Objective To observe the clinical efficacy and safety of apatinib in the treatment of advanced malignant tumors and to analyze the prognostic indicators affecting the survival of patients. Methods A total of 100 patients with advanced malignant tumors who were treated with apatinib at Jinan Central Hospital Affiliated to Shandong University from February 2015 to July 2018 were enrolled and their data were analyzed retrospectively. The clinical efficacy was evaluated and the related adverse reactions were recorded. Single and multiple factor analyses were performed by Cox regression model. The predictive factors of progression-free survival (PFS) and overall survival (OS) were analyzed. Results One-hundred patients with advanced malignant tumors who were treated with second-line and above treatment were collected. All patients were assessable for response, no complete response was observed, 22 patients (22%) achieved partial remission, 58 patients (58%) in stable disease, and 20 patients (20%) appeared progressive disease. The objective response rate was 22% (22/100), the disease control rate was 80% (80/100), the median PFS was 3.6 months (95%CI: 2.7-4.5 months), and the median OS was 7.0 months (95%CI: 4.7-9.3 months). Univariate analysis showed that Eastern Cooperative Oncology Group (ECOG) score (HR=0.340, 95%CI: 0.211-0.546, P<0.001), tumor primary site (HR=1.757, 95%CI: 1.053-2.932, P=0.031), neutrophil to lymphocyte ratio (NLR) (HR=0.389, 95%CI: 0.227-0.666, P=0.001), hemoglobin (HR=1.696, 95%CI: 1.023-2.813, P=0.041) and proteinuria (HR=1.790, 95%CI: 1.105-3.155, P=0.044) were related to PFS; age (HR=2.082, 95%CI: 1.320-3.285, P=0.002), ECOG score (HR=0.206, 95%CI: 0.123-0.344, P<0.001), tumor primary site (HR=1.784, 95%CI: 1.077-2.954, P=0.025), NLR (HR=0.410, 95%CI: 0.238-0.704, P=0.001), hemoglobin (HR=1.958, 95%CI: 1.175-3.264, P=0.010) and albumin (HR=0.467, 95%CI: 0.277-0.787, P=0.004) were related with OS. Multivariate analysis showed that PFS was related to ECOG score (HR=0.254, 95%CI: 0.123-0.523, P<0.001) and NLR (HR=0.378, 95%CI: 0.161-0.888, P=0.026), and OS was related to ECOG score (HR=0.147, 95%CI: 0.067-0.326, P<0.001), NLR (HR=0.327, 95%CI: 0.140-0.765, P=0.010) and hemoglobin (HR=1.975, 95%CI: 1.101-3.543, P=0.022). In term of safety, the most common adverse events among 100 cases of treated patients with advanced malignant tumors were hypertension (53, 53%), anorexia (51, 51%), fatigue (51, 51%) and anemia (50, 50%), among which the most common ones of grade 3 and 4 were hypertension (10, 10%), thrombocytopenia (8, 8%), leukopenia (7, 7%) and hand-foot syndrome (6, 6%). Conclusion Apatinib has certain clinical efficacy and manageable adverse events in the treatment of advanced malignant tumors at and above second-line treatment. ECOG score and NLR are independent predictors of PFS and OS in patients with advanced malignant tumors treated with apatinib. Key words: Neoplasms; Treatment outcome; Drug-related side effects and adverse reactions; Apatinib; Prognosis

AB009. S009. Effect of endoscopic iodine 125 seeds brachytherapy on advanced pancreatic cancer: experience of single center

Background: Pancreatic cancer (PC) is a highly lethal malignancy of digestive system, and nearly 80 percent of PC patients have lost the chance of surgery due to the lack of early diagnosis. For these patients, the only effective treatment (chemotherapy) is largely limited by drug resistance. Therefore, it is urgent to develop new therapy for PC. Endoscopic ultrasound (EUS) guided Iodine 125 (I125) seeds brachytherapy is a novel way of radiotherapy, and its role in the treatment of advanced malignant tumors is not fully explored. This study is to explore the efficacy of I125 brachytherapy on advanced pancreatic cancer.

Quality of life after I-125 seed implantation using computed tomography and three-dimensional-printed template guidance in patients with advanced malignant tumor.

I-125 seed implantation has been widely applied in the local treatment of advanced malignant tumor. It has the advantages of providing a high dose of treatment to the target sites and low dose to normal tissues. It has been mostly applied as palliative treatment for recurrences in advanced malignant tumor (except for prostate cancer), suppressing tumor development and improving the quality of life of patients. The objective of this study was to investigate changes in quality of life for patients with advanced malignant tumor after receiving I-125 seed implantation using a three-dimensional (3D)-printed individualized template and computed tomography (CT) guidance. In this prospective study, convenience sampling was applied for patients with advanced tumors attending a tertiary hospital. The European Organization for Research on Treatment of Cancer Quality of Life Questionnaire-C30 was involved to assess quality of life. Patients completed the questionnaire before and 24 h after seed implantation. The questionnaire of 1 and 3 months after seed implantation was completed by telephonic follow-up. A total of 42 patients were included (24 males and 18 females), with an average age of 58.86 ± 14.13 years (ranged 25-91 years). The average scale score after seed implantation was higher than that of before implantation. The order was the average scale score 1 month after seed implantation >3 months after seed implantation >24 h after seed implantation. The results suggested that the quality of life could be improved with I-125 seed implantation using a 3D-printed individualized template under CT guidance in patients with the advanced malignant tumor.

Efficacy and safety of bone cement in treatment of advanced malignant tumors with vertebral metastasis

目的 观察骨水泥治疗晚期恶性肿瘤椎体转移的效果和安全性。 方法 对2010年1月至2014年12月接受骨水泥治疗的30例恶性肿瘤椎体转移患者进行回顾性分析。分别在骨水泥治疗前24 h及术后12 h、24 h、7 d、1个月、3个月、6个月、12个月利用测量数值评分量表（NRS）评估患者疼痛的缓解情况，利用Karnofsky评分法评估患者生命质量的改善情况，并观察有无严重的并发症。 结果 所有患者在接受骨水泥治疗后疼痛均缓解。NRS评分提示治疗后12 h患者疼痛明显缓解[（2.13±0.92）分]，24 h疼痛控制稳定[（1.77±0.92）分]，随访期间所有接受骨水泥治疗的椎体均无疼痛复发。Karnofsky评分提示治疗后12 h[（66.67±9.07）分]开始30例患者生命质量均有不同程度改善，治疗后6个月开始部分患者生命质量开始下降，均死于肿瘤复发转移。其中1例患者发生无症状骨水泥椎体外渗漏，其余患者均无并发症发生。随访期间所有患者均无局部肿瘤复发。 结论 骨水泥能快速缓解恶性肿瘤骨转移引起的疼痛，改善患者生命质量，且具有良好的安全性。

Mitomycin-C in the treatment of advanced malignant tumors

Mitomycin-C in the treatment of advanced malignant tumors