Effectiveness and safety of camrelizumab combined with chemotherapy in nonsquamous nonsmall cell lung cancer as the second-line therapy: A retrospective analysis.

Background: The role of camrelizumab combined with chemotherapy as the second-line therapy in nonsquamous nonsmall cell lung cancer (NSCLC) remains unverified. The retrospective study investigated efficacy and safety of camrelizumab combined with chemotherapy in the treatment of nonsquamous NSCLC as the second-line therapy. Subjects and Methods: Patients of nonsquamous NSCLC who were already discharged or died of the First Affiliated Hospital of Anhui Medical University between August 2019 and September 2020. According to the treatment method, the patients who received chemotherapy were denoted as the C group and those who received camrelizumab plus chemotherapy were denoted as the C&C group. Statistical Analysis Used: Patients responses were statistically analyzed. The Cox proportional hazards regression model was used in the assessment of the prognostic value of factors. Furthermore, adverse event evaluation was estimated. Results: Of the 60 patients with nonsquamous NSCLC included in the research, 29 patients received chemotherapy, and 31 patients received camrelizumab plus chemotherapy. The objective response rate was 13.79% and 32.26% for chemotherapy and camrelizumab plus chemotherapy groups, and the disease control rate was 72.41% and 80.65%. The median progression-free survival (mPFS) in camrelizumab plus chemotherapy group was obviously higher than that in the chemotherapy group (9.67 vs. 6.87 months, P = 0.01). The median overall survival of the camrelizumab plus chemotherapy was longer than the chemotherapy (10.89 vs. 7.95 months, P < 0.01). In the current treatment, radiotherapy and smoking were independent risk factors for the mPFS of patients with nonsquamous NSCLC. The occurrence of adverse events was similar between chemotherapy and camrelizumab plus chemotherapy groups. Conclusions: Camrelizumab combined with chemotherapy was an effective regimen with manageable toxicity in treating nonsquamous NSCLC as the second-line therapy.

Anlotinib plus nab-paclitaxel/gemcitabine as first-line treatment prolongs survival in patients with unresectable or metastatic pancreatic adenocarcinoma: a retrospective cohort.

Background: The timely addition of anlotinib to the nab-paclitaxel/gemcitabine regimen may further increase the treatment efficacy for pancreatic adenocarcinoma (PDAC), which has not yet been reported. Therefore, we aimed to compare the efficacy and safety of anlotinib plus nab-paclitaxel/gemcitabine in the first-line treatment of patients with unresectable or metastatic PDAC. Methods: This was a retrospective cohort of patients with unresectable or metastatic PDAC performed in The First Affiliated Hospital of Anhui Medical University from August 17, 2019 to April 3, 2021. Patients who received anlotinib plus nab-paclitaxel/gemcitabine treatment were defined as the anlotinib plus chemotherapy group and patients who received nab-paclitaxel/gemcitabine were defined as the chemotherapy group. The primary outcomes were progression-free survival (PFS) and overall survival (OS). Secondary outcomes were the objective response rate (ORR), the disease control rate (DCR), and toxic side effects. Clinical data and follow-up information were mainly obtained from hospital records or by telephone. Results: A total of 33 patients were included in this study, with 17 cases in the anlotinib plus chemotherapy group and 16 cases in the chemotherapy group. The median PFS (mPFS) of the anlotinib plus chemotherapy group was 5 months while the mPFS of the chemotherapy group was 2.7 months (P=0.0220). The median OS (mOS) of the anlotinib plus chemotherapy group was 9 months while the mOS of the chemotherapy group was 6 months (P=0.0060). The 3-month and 6-month PFS, and the 6- and 12-month OS of the anlotinib plus chemotherapy group were significantly higher than those of the chemotherapy group (P<0.05). The proportion of patients with hematological toxicities in the anlotinib plus chemotherapy group was not significantly higher than that in the chemotherapy group. Conclusions: Anlotinib plus nab-paclitaxel/gemcitabine as a first-line treatment regimen is safe and may prolong survival compared with nab-paclitaxel/gemcitabine chemotherapy in patients with unresectable or metastatic PDAC. Randomized controlled trials with large sample sizes are warranted to further evaluate the treatment effects of anlotinib in PDAC. Keywords: Pancreatic adenocarcinoma (PDAC); anlotinib; nab-paclitaxel/gemcitabine; progression-free survival (PFS); overall survival (OS).

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

Background: Sintilimab 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. Methods: We 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. Results: A 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. Conclusions: Sintilimab 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.

PCAT1/miR-129/ABCB1 axis confers chemoresistance in non-small cell lung cancer.

Long noncoding RNA prostate cancer-associated transcript 1 (PCAT1) is oncogenic and causes progression of non-small cell lung cancer (NSCLC). We hypothesized that PCAT1 might be involved in the acquisition of chemoresistance of NSCLC cells to treatment with cisplatin (DDP). Here, we show that PCAT1 and ATP-binding cassette sub-family B member 1 (ABCB1) are highly expressed in NSCLC tissues and cell lines, and regulate the growth and apoptosis of these cells. Compared with those in DDP-sensitive patients, PCAT1 and ABCB1 are highly expressed in the tumors of DDP-resistant patients, and such overexpression correlates with a shorter overall survival of these patients. Knockdown of PCAT1 or upregulation of miR-129 led to apoptosis and sensitized the DDP-resistant cells to DDP. The 3' UTR activity of PCAT1 and ABCB1, which was increased by PCAT1 overexpression, was shown to harbor an miR-129 binding site. DDP resistance is induced by elevated ABCB1 expression, which involves binding of miR-129 in DDP resistant cells. These findings suggest that the PCAT1/miR-129/ABCB1 axis may be a potential target for the treatment of DDP-resistant oat cell cancer.

Clinical efficacy analysis of Osimertinib treatment for a patient with leptomeningeal metastasis of EGFR+ non-small cell lung cancer without the T790M mutation.

BACKGROUND: To find the method of therapy of leptomeningeal metastasis (LM) to non-small cell lung cancer (NSCLC) patient with EGFR mutation (EGFR+) but without T790M mutation. METHODS: A retrospective analysis was reviewed for 5 NSCLC patients with EGFR+ who develop to LM from January 2018 to February 2019 in our hospital. RESULTS: All five NSCLC cases were adenocarcinoma, four cases were verified existed EGFR mutation with 19 exon deletion in the first diagnosed by biopsy tissue, the other tissue was verified 21 exon mutation. Two cases were initially diagnosed with LM, and the other three cases were found metastasis with leptomeningeal respectively after 64, 3 and 4 months when the lung cancer was diagnosed. There were not verified to exist T790M mutation with EGFR+ when all the five cases developed to LM. The major symptom was headache and blurred vision. In the image scanning, two cases were not revealed, but other three cases show that multiple metastatic lesions with brain and meninges. All patients were identified existed adenocarcinoma cells in cerebrospinal fluid (CSF). Four cases were treated by the first epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) and joint therapy including chemotherapy and radiotherapy, and the other case was treated by temozolomide and intrathecal chemotherapy in their earlier therapy. The curative effect was significant when they took osimertinib orally 80 mg once a day, for the disease progressing. The neurological symptoms were relieved in patient about 5-10 days after osimertinib treatment. The remission time was 10, 7, 7, 5, 4 months respectively until last following time to June 2019. The survival time was respectively 74, 7, 27, 18, and 4 months. The side effects were not increased. CONCLUSIONS: Whether EGFR+ with T790M mutation was positive or negative, osimertinib is an effective drug and can improve quality of life and prolong the survival for NSCLC patient with EGFR mutation to progress LM.

An open-labeled, randomized, multicenter phase IIa study of gambogic acid injection for advanced malignant tumors.

BACKGROUND: Gambogic acid is a pure active compound isolated from the traditional Chinese medicinal plant gamboge (Garcinia morella Desv.). Based on the preliminary results of a phase I study, this phase IIa study compared the efficacy and safety of different dosage schedules of gambogic acid in patients with advanced malignant tumors. METHODS: Patients with advanced or metastases cancer who had not received any effective routine conventional treatment or who had failed to respond to the existing conventional treatment were randomly assigned to receive either 45 mg/m(2) gambogic acid intravenously from Days 1 to 5 of a 2-week cycle (Group A), or 45 mg/m(2) every other day for a total of five times during a 2-week cycle (Group B). The primary endpoint was objective response rate (ORR). RESULTS: Twenty-one patients assigned to Group A and 26 to Group B were included in the final analysis. The ORRs were 14.3% in Group A and 0% in Group B. It was not possible to analyze the significant difference because one of the values was zero. The disease control rates (DCRs) were 76.2% in Group A and 61.5% in Group B (P = 0.0456). The observed adverse reactions were mostly Grades I and II, and occurred in most patients after administration of the trial drug. There was no significant difference in the incidence of adverse reactions between the two arms. CONCLUSIONS: The preliminary results of this phase IIa exploratory study suggest that gambogic acid has a favorable safety profile when administered at 45 mg/m(2). The DCR was greater in patients receiving gambogic acid on Days 1 - 5 of a 2-week cycle, but the incidence of adverse reactions was similar irrespective of the administration schedule.

The screening of volatile markers for hepatocellular carcinoma.

BACKGROUND: Breath analysis became promising for noninvasive diagnoses of cancer with sophisticated spectrometry technology introduced. This study aimed to screen volatile markers for hepatocellular carcinoma (HCC). METHODS: Breath samples were collected from 30 HCC patients who were comorbid with type B hepatitis and cirrhosis and from 27 hepatocirrhosis patients and 36 healthy persons, both taken as controls. The volatile organic compounds in the samples were analyzed with gas chromatography/mass spectrometry and the markers were selected by comparing their levels between groups. Each of the markers was evaluated by receiver operating characteristic (ROC) curves and a discriminant function using the markers was established. The relationships of alpha-fetoprotein (AFP) levels and clinical stages with the concentrations of the markers were also investigated. RESULTS: 3-Hydroxy-2-butanone, styrene, and decane were screened as potential markers, among which 3-hydroxy-2-butanone was found to have the best diagnostic value. The diagnostic function using these markers had a sensitivity of 86.7% and a specificity of 91.7% between HCC patients and normal controls and a sensitivity of 83.3% and a specificity of 91.7% by cross-validation. No statistically significance (P > 0.05) was found for the concentration differences of these markers between HCC patients with AFP >400 or <400 microg/L or between stage I-II and stage III-IV patients. CONCLUSION: These volatile organic compounds could be useful as breath markers of HCC patients, independent of AFP levels or clinical stages. IMPACT: Breath analysis could be useful for early diagnosis of HCC, especially for AFP-negative HCC.

Quantitative breath analysis of volatile organic compounds of lung cancer patients.

Due to state-of-art analytical techniques, non-invasive exhaled volatile organic compounds (VOCs) analysis has become a potential method for early diagnosis of lung cancer. We collected breath samples from 43 patients with non-small cell lung cancer (NSCLC) and 41 normal controls using Tedlar gas bags. The VOCs were extracted with solid phase micro-extraction (SPME) and analyzed by gas chromatography (GC)/mass spectrometry (MS). The number of VOCs detected in each breath sample ranged from 68 to 114. Among the VOCs 1-butanol and 3-hydroxy-2-butanone were found at significantly higher concentrations in breath of the lung cancer patients compared to the controls. VOCs levels were not significantly different between early stage lung cancer patients and late stage lung cancer patients. Lung adenocarcinoma was significantly related to higher VOCs concentrations in the breath. Our data showed that 1-butanol and 3-hydroxy-2-butanone in breath could possibly be taken as useful breath biomarkers for discerning potential lung cancer patients and VOCs analysis could be used as a complementary test for the diagnosis of lung cancer.