Adverse Reactions Of Grade Research Articles

Feasibility and Tolerability of Anlotinib Plus PD-1 Inhibitors for Previously-Treated Advanced Non-Small Cell Lung Cancer: A Retrospective Exploratory Study.

Anlotinib demonstrated encouraging therapeutic activity as third-line treatment for patients with advanced non-small cell lung cancer (NSCLC). Programmed cell death protein 1 (PD-1) inhibitors also exhibited promising and durable response against previously-treated advanced NSCLC. Therefore, the present study aimed to determine the feasibility and safety of anlotinib plus PD-1 inhibitors for previously-treated NSCLC in clinical practice. This retrospective study included 56 patients with advanced NSCLC treated with systemic treatment previously. Patients included were treated with anlotinib plus PD-1 inhibitors in clinical practice. Therapeutic outcomes of the patients were evaluated radiologically using target lesions, and the prognostic outcomes were generated by follow-up. Adverse reactions experienced throughout the treatment were documented and analyzed. Between August 2018 and November 2022, 56 patients with advanced NSCLC were eligible to participate in this study consecutively. Therapeutic outcomes resulted in an overall response rate of 28.6% [95% confidence interval (CI): 17.3%-42.2%] and a disease control rate of 91.1% (95% CI: 80.4%-97.0%). Furthermore, this combination regimen among the 56 patients yielded a median progression-free survival (PFS) of 6.5 months (95% CI: 4.81-8.19) and a median overall survival (OS) of 15.8 months (95% CI: 10.23-21.37), respectively. And the median duration of response (DoR) among patients who responded was 8.3 months (95% CI: 4.38-12.22). Additionally, adverse reactions of all grades throughout the treatment were observed in 50 patients (89.3%), and adverse reactions of grade ≥3 were detected in 23 patients (41.1%). Fatigue, hypertension, diarrhea, nausea, and vomiting were the most common adverse reactions. Association analysis between PFS and baseline characteristic subgroups indicated that ECOG score and number of metastatic lesions might be potential predictors of PFS in the exploratory analysis. Anlotinib plus PD-1 inhibitors demonstrated a tolerable safety profile and encouraging therapeutic activity as subsequent-line therapy in patients with advanced NSCLC. This conclusion should be confirmed in prospective large-scale clinical trials subsequently.

Feasibility and Safety of PD-1 Blockades Among Elderly Patients with Metastatic Esophageal Squamous Cell Carcinoma: A Real-World Study.

This study aimed to identify the effectiveness and safety of PD-1 blockades among elderly patients with metastatic esophageal squamous cell carcinoma (ESCC) clinically. A total of 78 elderly patients with previously treated metastatic ESCC aged ≥65 years who received PD-1 blockades monotherapy were included retrospectively. Demographic characteristics, therapeutic effectiveness and adverse reactions of the elderly patients who underwent PD-1 blockade therapy were recorded. Regular follow-up was conducted for all patients. The analysis aimed to identify potential risk factors for OS by examining the correlation between prognosis and subgroups based on baseline characteristics. The median age of the 78 elderly patients was 73 years, ranging from 65 to 87 years. Among the 78 patients, 18 cases showed partial response, 26 cases had stable disease, 29 cases experienced progressive disease and 5 cases were not assessable for response, yielding an ORR of 23.1%, a DCR of 56.4%. The prognostic outcomes indicated that among the 78 patients with metastatic ESCC who received PD-1 blockades, the median PFS was 3.1 months [95% confidence interval (CI): 1.64-4.56], and the median OS was 10.9 months (95% CI: 6.02-15.78), 24-month OS rate was 22.7% (95% CI: 12.8-34.2%). In terms of the safety profile, among the 78 patients with metastatic ESCC during PD-1 blockades single-agent treatment, a total of 61 patients (78.2%) experienced any grade adverse reactions and the incidence of grade ≥3 adverse reactions were 20.5%. Briefly, the common adverse reactions manifested as fatigue (32.1%), gastrointestinal reaction (24.4%), diarrhea (19.2%), anemia (17.9%) and rash (16.7%). Overall tolerability of PD-1 blockade monotherapy in elderly patients with metastatic ESCC was acceptable and manageable. PD-1 blockades single agent demonstrated encouraging effectiveness and acceptable safety profile for elderly patients with previously treated metastatic ESCC in clinical practice. Prospective study should be performed to elucidate the conclusion in this study subsequently.

Preclinical and early clinical data of ZN-1041, a best-in-class BBB penetrable HER2 inhibitor to treat breast cancer with CNS metastases.

1040 Background: HER2+ breast cancer brain metastases (BCBM) is an aggressive malignancy with high prevalence and limited treatment options. ZN-1041 is a best-in-class HER2 inhibitor designed to be delivered across the blood-brain barrier (BBB) with high selectivity and broader safety margin to treat HER2+ BCBM. Methods: Brain penetration of ZN-1041 and other approved HER2 tyrosine kinase inhibitors (TKI) were evaluated. Anti-tumor activity of ZN-1041 alone or in combination were evaluated in xenograft models. ZN-A-1041-101 (NCT04487236) is an on-going phase 1, multicenter, open-label study. The study comprises first-in-human dose escalation of ZN-1041 monotherapy (phase 1a) in HER2+ solid tumor patients (pts) with or without BM, dose escalation (phase 1b) and expansion (phase 1c) of ZN-1041 in combination with capecitabine and trastuzumab in pts with HER2+ BCBM (including active BM). The primary objective was safety and tolerability. The secondary objective includes pharmacokinetics and anti-tumor response including ORR per RECIST 1.1 and intracranial ORR (iORR) per RANO-BM. Results: Unlike currently approved HER2 TKIs which are strong human efflux transporter P-gp and BCRP substrates, ZN-1041 is not a substrate of either and has high BBB permeability, therefore predicted to have good BBB penetration. ZN-1041 alone demonstrated dose-dependent and significant anti-tumor activity when compared to tucatinib in BM model. ZN-1041 could synergize with capecitabine and trastuzumab to demonstrate significantly improved intracranial efficacy in BM models, while maintaining good tolerability. In total, 21 HER2+ mBC pts were enrolled to complete phase 1a and 1b. No dose-limiting toxicities or treatment-related SAE were observed across all dose levels. PK exposure was increased with dose escalation and Kpuu,CSF of ZN-1041 was 4.9. In ZN-1041 monotherapy, the overall ORR and iORR were 50% in TKI naïve, unequivocal HER2+ pts. The longest treatment duration was 15 months. As of data cutoff (Dec 02, 2022), totally 35 TKI naïve, HER2+ BCBM pts with median 2L treatments were enrolled for phase 1c and all pts were well tolerated to date. Adverse reactions of grade 3 or higher (≥5%) were hepatic function impairment (8.7%), headache (8.7%), hyperbilirubinemia (5.7%), ALT increased (5.7%), AST increased (5.7%), GGT increased (5.7%) and WBC decreased (5.7%). Among 19 BCBM pts with at least twice tumor assessment, the overall ORR was 78.9% (95% CI: 54.4–93.9) and iORR was 73.7% (95% CI: 48.8–90.9), DCR was 100%. In addition, 6 pts completed first tumor assessment and 5 achieved PR and 1 had SD per RECISIT 1.1. Conclusions: Encouraging efficacy and tolerability was observed for ZN-1041 monotherapy or combined with capecitabine and trastuzumab in TKI naïve, HER2+ BCBM patients. A Phase 2 pivotal trial for HER2+ BCBM with ZN-1041, capecitabine and trastuzumab combination therapy is planned. Clinical trial information: NCT04487236 .

Willingness to receive COVID-19 vaccination and adverse effects after vaccination in breast cancer survivors during the COVID-19 pandemic: a cross-sectional retrospective study of a Chinese population.

Breast cancer (BC) patients have a higher mortality rate after COVID-19 infection, but data on vaccination of BC patients and attitude towards COVID-19 vaccination and safety after vaccination are lacking. We wanted to understand the willingness and factors of BC survivors to receive a COVID-19 vaccine, and their adverse reactions. The purpose is to judge the safety of vaccination, and find strategies to promote vaccination in BC patients. Offline and online questionnaire surveys were provided in outpatient clinics and on an online follow-up platform, respectively, to collect information. Factors influencing vaccination willingness were analyzed by univariate and multivariate logistic regression. All statistical tests were performed bilaterally, and a P value <0.05 was considered statistically significant. Patients who have been vaccinated need to fill in questions about the impact on quality of life after vaccination, the type and frequency of vaccination, and side effects. A total of 497 valid questionnaires were collected; 289 (58.1%) BC survivors were vaccinated with a COVID-19 vaccine, and 379 (76.26%) BC survivors had a fully or basically accepting attitude toward vaccination. Survivors over 70 years of age, educated only to high school level, and those receiving chemotherapy had significantly lower levels of acceptance of COVID-19 vaccines. Multivariate logistic regression analyses suggested that treatment status and cognitive attitude were independent factors influencing COVID-19 vaccination among BC survivors. The main reason for being vaccinated was "doctor recommendation" (57.26%). Unwillingness to receive a COVID-19 vaccine was mainly due to "the unknown safety of the vaccine in cancer patients" (67.80%). A total of 97.56% of the survivors believed that vaccination had no or almost no effect on their quality of life. Among the BC survivors, 18 (6.23%) had adverse reactions after vaccination. All adverse reactions were grade 1 or 2, and no adverse reactions of grade 3 or above were reported. The adverse reactions reported by 15 survivors (83.33%) markedly improved within 1 week. In terms of cognitive attitudes toward COVID-19 vaccines, elderly individuals and those with a lower education level were less receptive to vaccination. Therefore, attention to elderly survivors can help improve the vaccination rate.

Comparison of surgery with or without adjuvant radiotherapy in treating central neurocytoma: a single-center retrospective real-world study.

To investigate the efficacy and safety of adjuvant radiotherapy (RT) in patients with central neurocytoma (CN). The study included 68 patients with CN retrospectively, wasfurther divided into surgery + RT group (31 patients) and surgery alone group (37 patients). Progression-free survival (PFS), overall survival (OS), and adverse reactions (AEs) were compared between the two groups. The median follow-up duration was 82.2 (interquartile range, 64.7-104.5) months. Patients in the surgery + RT group tended to have longer PFS than those in the surgery alone group (5-year PFS rate: 92.7% vs. 86.3%; P = 0.074). There was no significant difference in OS between the two groups (5-year OS rate: 96.8% vs. 94.3%; P = 0.639). Subgroup analysis revealed a significant improvement in PFS in patients receiving RT after surgery in patients who underwent subtotal resection (STR) (P = 0.045). In the overall population, univariate multivariate analysis revealed that gross total resection (GTR) (P = 0.002), tumor location in the unilateral ventricle (P = 0.008), and MIB-1 (Ki-67)labeling index (LI) < 5% (P = 0.009) were favorable independent prognostic factors for PFS. Whereas tumor location in the unilateral ventricle (P = 0.043) was a favorable independent prognostic factor for OS. Moreover, RT patients experienced AEs (Grade 1-2, well-tolerated). Adjuvant RT in the treatment of CNs showed satisfactory safety, and postoperative RT could improve PFS in STR patients. Furthermore, GTR, tumor development in the unilateral ventricle, and MIB-1LI < 5% were found to be favorable factors affecting the prognosis of CNs.

Safety and Viral Shedding of Live Attenuated Influenza Vaccine (LAIV) in Chinese Healthy Juveniles and Adults: A Phase Ⅰ Randomized, Double-Blind, Placebo-Controlled Study.

This study was a randomized, double-blind, placebo-controlled study to evaluate the safety and viral shedding of live attenuated influenza vaccine (LAIV) in Chinese healthy juveniles and adults. A total of 80 Eligible volunteers were divided into two age groups (≥18 and 3-17 years old). Volunteers were randomly and equally assigned to the experimental group and placebo-controlled group by ratio of 3:1 in each age group. Vaccination was carried out in steps. Totally, 34 (56.67%) adverse events and 24 (40.00%) adverse reactions of the LAIV group were reported. Most adverse reactions were grade 1 and grade 2, and the incidence of adverse reactions that grade 3 was 5%. The most common local reaction was runny nose/nasal congestion (n = 4, 6.67%). And the most common general reaction was fever (n = 10, 16.67%). There were no statistically significant differences in the incidence of total adverse reactions, different grades of adverse reactions, and symptoms between the experimental group and placebo-controlled group. No severe adverse events were reported. Three subjects (5.00%) had been detected vaccine strains on the 3rd day after LAIV vaccination; one was type B and the other two were H3N2. Four subjects (6.67%) had been detected with vaccine strains on the 7th day after LAIV vaccination, all were H3N2. There were no subjects detected carrying the influenza virus on the 15th day after vaccination. There were no statistically significant differences in the positive rate of vaccine strains of influenza virus between the experimental group and placebo-controlled group. The vaccine was well tolerated and not associated with increased rates in adverse reactions or the occurrence of severe adverse events. Pathogenicity of shed vaccine virus to surrounding people was not observed. Thus, Phase Ⅱ study can be carried out as scheduled.

Neoadjuvant pegylated liposomal doxorubicin (PLD) plus cyclophosphamide followed by nab-paclitaxel (Nab-P) as primary chemotherapy continuously combined with dual HER2 blockage for HER2-positive breast cancer: A single-arm phase 2 trial (Brecan Trial).

e12622 Background: Despite that AC-THP regimen is one of the commonly used regimens for neoadjuvant treatment of HER2-positive breast cancer, previous studies showed that pCR rate rarely exceeds 70%. We hypothesized that prolonged dual anti-HER2 therapy can increase pCR rate in neoadjuvant therapy. In this study, we designed a single-arm trial of ACHP-THP regimen (continuous dual anti-HER2 therapy of trastuzumab and pertuzumab) in neoadjuvant therapy of HER2 positive breast cancer. To minimize adverse cardiovascular events, we used pegylated liposomal doxorubicin (PLD) and Nab-Paclitaxel (Nab-P) instead of doxorubicin and paclitaxel. We aimed to examine whether continuous dual anti-HER2 therapy can boost pCR rate in the neoadjuvant therapy. The cardiotoxicity was closely monitored when the anti-HER2 therapy was combined with PLD and Nab-P respectively. Methods: Upon approval by the Medical Ethics Committee of Xijing Hospital, patients with HER2-positive breast cancer (cT2-3/N0-1/M0) receiving neoadjuvant therapy, were enrolled. The patients were treated with PldCHP (pegylated liposomal doxorubicin 35mg/m2, cyclophosphamide 600mg/m2, trastuzumab 8 mg/kg loading, then 6 mg/kg, pertuzumab 840 mg loading, then 420 mg, iv, q3w) for 4 cycles followed by Nab-PHP (Nab-Paclitaxel 260mg/m2, trastuzumab 6 mg/kg, pertuzumab 420 mg, iv, q3w) for 4 cycles, with strict monitoring of cardiotoxicity. The primary endpoint was pCR rate, and secondary endpoint was cardiotoxicity during neoadjuvant therapy. Results: From January 2020 to October 2021, a total of 96 patients were recruited. Among the 96 patients with a median age of 49 (21-71), 58 patients were HR positive and 42 patients had positive lymph node status. Overall, the pCR rate was 80.2% (77/96). The ER-positive tumor achieved a higher pCR rate than ER-negative tumor (82.8% vs 76.3%, p=0.439), but the difference was statistically insignificant. Multivariate regression analysis showed that for participants older than 30, HER2 3+ (IHC) showed a statistically significant positive influence on pCR rate. The common adverse reactions of grade ≥3 were neutropenia (30.2%), asthenia (8.3%), and peripheral sensory neuropathy (7.3%). Left ventricular insufficiency was detected in 4 patients, and no cardiotoxic events higher than grade 2 occurred during the neoadjuvant therapy. There was no treatment-related death. Conclusions: The PldCHP---Nab-PHP regimen is a feasible and effective neoadjuvant therapy for early stage HER2-positive breast cancer, showing high pCR rate and acceptable cardiotoxicity. These results support a further random controlled trial testing for continuous dual anti-HER2 therapy combined with PLD in neoadjuvant or adjuvant therapy of HER2 positive breast cancer.

A phase II single-center single-arm study of PD-1 inhibitor in combination with albumin paclitaxel and apatinib as second-line treatment of metastatic gastric cancer (mGC).

e16024 Background: Immune checkpoint inhibitors have been approved for first- or third-line treatment of metastatic gastric cancer. However, pembrolizumab alone did not improve overall survival compared to second-line chemotherapy in the KEYNOTE-061 study. We aimed to explore the safety and efficacy of a three-drug regimen by carrying out a clinical study of PD-1 inhibitor combined with albumin paclitaxel and apatinib (VEGFR inhibitor) in the second-line treatment for patients with metastatic gastric cancer(mGC). Methods: This study was a single-center, single-arm phase II clinical study. patients harboring microsatellite stable (MSS) who had previously failed in first-line treatment were enrolled. The enrolled patients were given PD-1 inhibitor (PD-1 inhibitor selected according to the patients’ requirements) in combination with albumin paclitaxel (125 mg/m2 IV, D1, 8 days or 250 mg/m2 IV, D1, 250 mg and apatinib 250 or 500 mg orally for D1-21 days, every 3 weeks as a cycle). The primary endpoints were progression-free survival (PFS) and objective response rate (ORR), while the secondary endpoints were overall survival (OS) and safety (AEs), disease control rate (DCR). Results: From July 11, 2019 to December 1, 2021, a total of 23 patients were enrolled, of whom 10 had negative PD-L1 expression, 1 had PD-L1 &gt; 70% expression, and 4 had positive PD-L1 expression. Preliminary results showed 8 cases had partial response (PR), 10 cases had stable disease (SD), and 5 cases of progression disease (PD). ORR was 34.8% and DCR was 78.3%. The median PFS was 5.04 m, and the median OS was not reached. The main adverse reactions of grade 1 to 2 were bone marrow suppression (42.8%), hand-foot reaction (21.4%), hypertension (21.4%), gastrointestinal bleeding (13.0%), hypothyroidism (8.7%), and liver function damage (8.7%). No grade 3-4 adverse reactions were reported. Conclusions: PD-1 inhibitor combined with albumin paclitaxel and apatinib in the second-line treatment of metastatic gastric cancer showed certain efficacy and safety. At present, this study is ongoing to further confirm the anti-tumor effect and survival benefit of this regimen. Clinical trial information: NCT04182724.

Efficacy and Safety Evaluation of Sintilimab for Cancer Treatment: A Systematic Review and Meta-analysis of Randomized Controlled Trials

Objective: Meta analysis was used to explore the efficacy and safety of Sintilimab in the treatment of cancer. Methods: The databases of CNKI, VIP, Wanfang Data, PubMed, ScienceDirect, the Cochrane Library and EMBASE were searched by computer to collect the randomized controlled trials published as of March 2022. The retrieval work was completed by two researchers alone. They screened the literature and extracted the data according to the nanodischarge standard, using Revman 5.4 software. The included studies were statistically analyzed. Results: Six RCTs were included in this study, including 1,048 cases of Sintilimab and 711 cases of other anticancer drugs. Compared with the control group, the overall survival (HR = 1.64, 95% CI: 1.35–1.99, p < 0.00001) and progression free survival (HR = 1.89, 95% CI: 1.59–2.25, p < 0.00001) of cancer treated with Sintilimab were longer and more effective. Moreover, the risk ratio of any grade of adverse reactions (HR = 0.87, 95% CI: 0.74–1.03, p = 0.11) and above grade III adverse reactions (HR = 0.84, 95% CI: 0.67–1.06, p = 0.14) in the treatment of cancer with Sintilimab was lower and the safety was better. Conclusion: Compared with non-Sintilimab group, Sintilimab treatment can improve the clinical efficacy of tumor patients and has a lower incidence of adverse reactions. This treatment may be a promising treatment for cancer patients.

Efficacy and Safety of Acupuncture in the Treatment of Poststroke Insomnia: A Systematic Review and Meta-Analysis of Twenty-Six Randomized Controlled Trials.

Objective To evaluate the efficacy and safety of acupuncture in the treatment of poststroke insomnia. Methods PubMed, the Cochrane Library, Embase, Web of Science, China Biology Medicine (CBM), CNKI, VIP, and Wanfang databases were searched by computer from their inception to April 29, 2021, for collecting all randomized controlled trials of acupuncture in the treatment of poststroke insomnia. After two reviewers independently screened the literature, extracted the data, and evaluated the risk of bias in the included studies, the data were analyzed by RevMan 5.3 and STATA 16.0. The quality of outcomes was evaluated by the Grading of Recommendations Assessment, Development and Evaluation (GRADE). Results A total of 26 studies with 1874 cases were included, which had 942 cases in the treatment group and 932 cases in the control group. Meta-analysis results showed that, compared with oral medications alone, acupuncture alone or acupuncture combined with oral medications could improve the clinical effective rate and the sleep quality of patients, and the combined effects were RR = 1.21; 95% CI: 1.15, 1.27; P < 0.00001 and MD = 3.41; 95% CI: 2.40, 4.41; P < 0.00001, respectively. As for adverse reactions, the incidence of acupuncture alone or acupuncture combined with oral drugs was lower than that of oral drugs alone, which was safer and the combined effect was RR = 0.21; 95% CI: 0.09, 0.48; P=0.0002. Sensitivity analysis showed that the results were stable. We evaluated the quality of evidence with the GRADE system; the clinical effective rate was rated as “LOW,” the evidence grade of PSQI score was “LOW,” and the evidence grade of adverse reactions was “Very LOW.” Conclusion Acupuncture alone or acupuncture combined with oral drugs is more effective and safer than oral drugs alone in the treatment of poststroke insomnia, which is suitable to promote in clinical practice.

Whole-Brain Radiotherapy Combined With Anlotinib for Multiple Brain Metastases From Non-small Cell Lung Cancer Without Targetable Driver Mutation: A Single-Arm, Phase II Study.

Background:Existing evidence demonstrates that radiotherapy and antiangiogenic drugs have synergistic antitumour effects and may be a promising treatment option for patients with solid tumour. Thus, we performed a phase II trial to evaluate the efficacy and safety of whole-brain radiotherapy (WBRT) combined with anlotinib for multiple brain metastases (BMs) from non-small cell lung cancer (NSCLC) without targetable driver mutations.Methods:Patients with multiple BMs (⩾3) from NSCLC without targetable driver mutations who failed to respond to at least first-line chemotherapy were enrolled. Eligible patients received WBRT (30 Gy/10 f, 5 f/week) and anlotinib (12 mg/day, day 1-14 of 21 days per cycle, 2 cycles) until disease progression or treatment intolerance. The primary endpoint was intracranial objective response rate (iORR) and secondary endpoints included intracranial progression-free survival (iPFS), disease control rate (DCR), overall survival (OS), and safety.Results:Between April 2019 and March 2021, 21 patients were enrolled in the trial, of which 12 were aged ⩾60 years (57.1%), 13 were men (61.9%), 7 had an Eastern Cooperative Oncology Group Performance Status score of 0 to 1 (81.0%), 18 had adenocarcinoma (85.7%), and 11 had ⩾6 BMs (52.4%). Of the 21 evaluable patients, the iORR was 66.7% (1 complete response + 13 partial response [PR]), and 28.6% (7PR) had extracerebral lesions. The DCRs for intracerebral and extracerebral lesions were 90.5% and 81.0%, respectively. The iPFS and OS were 10.3 months (95% confidence interval [CI]: 0-24.8 months) and 13.4 months (95% CI: 0-27.9 months), respectively. The most frequently observed toxicities were loss of appetite (61.9%), hypertension (52.4%), fatigue (47.6%), diarrhoea (28.6%), vomiting (19.0%), dizziness (42.9%), and headache (33.3%). None of the patients developed grade 4 or higher grade adverse reactions.Conclusions:Anlotinib combined with WBRT is effective and well tolerated in patients with multiple BMs (⩾3) from NSCLC without targetable driver mutations. Therefore, further validation studies are required.Clinical trial registration number: ChiCTR 1900027769

Randomized phase III study comparing the first-line chemotherapy regimens in patients with driver mutation-negative advanced non-small cell lung cancer and poor performance status complicated with chronic obstructive pulmonary disease.

BackgroundPatients with non-small cell lung cancer (NSCLC) complicated with chronic obstructive pulmonary disease (COPD) with poor performance status (PS) are common in clinical practice with few related studies. Present studies have found that weekly low-dose docetaxel or gemcitabine combined with platinum is suitable for elderly or poor PS patients with advanced NSCLC.MethodsUntreated advanced driver mutation-negative NSCLC patients with COPD and PS ≥2 were enrolled in this double-blind randomized trial. Both groups controlled their COPD symptoms according to the GOLD guidelines. The anti-tumor regimens included docetaxel (37.5 mg/m2, D1, D8)/carboplatin (AUC 5.0) (DC group) and gemcitabine (1,000 mg/m2, D1, D8)/carboplatin (AUC 5.0) (GC group) were used every 3 weeks with continuous chemotherapy for 4–6 cycles or until disease progression. The primary endpoints were progression-free survival (PFS), and overall survival (OS).ResultsAmong the 52 patients (DC, n=25; GC, n=27), the median follow-up time was 12.3 months. There was no significant difference in tumor overall response rate (ORR; DC, 20.0% vs. GC, 22.2%, P=0.845) and disease control rate (DCR; DC, 72.0% vs. GC, 74.1%, P=0.064) between the 2 groups. The median PFS (GC, 6.5 vs. DC, 5.5 months; P=0.296) and the median OS (GC, 14.9 vs. DC, 12.3 months; P=0.548) of the GC group was slightly longer than the DC group. The main adverse reactions were myelosuppression and there were few adverse reactions of grade 3–4. Compared with the anti-tumor therapy only group in previous literature, the median PFS in this study was longer (6.2 months, 95% CI: 3.533–6.733 vs. 3.5 months, 95% CI: 2.432–4.568; P=0.589). There was also no significant difference in median OS and median PFS between the 2 groups (14.0 vs. 15.0 months, P=0.718). Chemotherapy cycle (P<0.001) was an independent prognostic factor for PFS, while chemotherapy cycle (P=0.011) and PS (P=0.041) were independent prognostic factors for OS.ConclusionsWeekly low-dose docetaxel or gemcitabine combined with carboplatin chemotherapy regimens can yield survival benefits and a tolerable safety profile in patients with driver mutation-negative advanced NSCLC and poor PS complicated with COPD, with no significant difference between the two regimens.Trial RegistrationChinese Clinical Trial Registry ChiCTR-IPR-15006164.

Preliminary Study of Chidamide Combined with Hematopoietic Stem Cell Transplantation in the Treatment of Childhood Acute T-Lymphoblastic Leukemia

To investigate the efficacy and safety of combination chidamide and hematopoietic stem cell transplantation (HSCT) in the treatment of childhood acute T lymphoblastic leukemia (T-ALL). Seven children with acute T lymphoblastic leukemia received hematopoietic stem cell transplantation in SUN Yat-Sen Memorial Hospital of SUN Yat-Sen University were selected. 7 cases of T-ALL were divided into 2 groups: HSCT plus chidamide-treated group (4 cases) and traditional HSCT-treated group (3 cases) as control. The incidence of GVHD and other related complications, as well as implantation, recurrence and survival were compared between the two groups, and the side effects of chidamide were observed. All the patients were follow-up until January 2019. All the 7 patients were alive and, there was no difference in the incidence of acute GVHD between the HSCT plus chidamides treated group and the traditional HSCT-treated group. The implantation rate of HSCT was 100%, and there were no recurrence occurred. During the application of chidamide, 3 cases showed adverse reactions, of which 2 cases had adverse reactions of grade 3 or higher, and 2 cases were hematological adverse reactions (neutropenia, thrombocytopenia), other adverse reactions were non-hematologic adverse reactions (transaminase elevation, fatigue, nausea, vomiting), there were no serious adverse reactions occurred. In the HSCT plus chidamide-treated group, 2 cases were found that mature lymphocytes were not expressed by tumors, during examing for minimal redidaul disease (MRD). Compared with the immunophenotype and TCR rearrangement at first diagnosis, the results did not support the source of residual T-ALL tumor cells. During the review of MRD, it was found that the abnormal T cells showed an increasing trend, indicating that chidamide might induce leukemia cell differentiation through some pathways. Hematopoietic stem cell transplantation is still an effective method to cure children's T-ALL. In some cases, abnormal T-cell nonclonal amplification occurs during the application of chidamide, and the children with T-ALL can tolerable adverse reactions of chidamide.

Influence of Hypertension on the Survival of Non-Small Cell Lung Cancer Patients with Type 2 Diabetes Mellitus.

BackgroundHypertension and diabetes mellitus (DM) are both the risk factors for cancer. This study aimed to explore the prognostic value of fasting blood glucose (FBG) and hypertension in type 2 DM (T2DM) patients with advanced non-small cell lung cancer (NSCLC) who had received chemotherapy treatment.Material/MethodsThere were 181 advanced NSCLC patients with T2DM between 2010 and 2019 included in this study. Their laboratory and clinical data were retrospectively analyzed. The predictive value of FBG and hypertension was evaluated. The Kaplan-Meier method was used to evaluate progression-free survival (PFS).ResultsThe median PFS was 168.0 days (95% CI: 137.9–198.7 days) in patients with FBG ≥7 mmol/L compared to 154.0 days (95% CI: 126.7–181.3 days) for patients with FBG <7 mmol/L (hazard ratio [HR]=1.054; 95% CI: 0.7669–1.452; P=0.7447). Median PFS was longer in non-hypertensive patients than in hypertensive patients [179.0 days (95% CI: 137.3–220.7 days) versus 128.0 days (95% CI: 96.3–159.7 days); P=0.0189]. The existence of hypertension (HR=1.478; 95% CI: 1.063–2.055; P=0.020) was an independent predictor for shorter PFS in the multivariate analysis. Decreased hemoglobin was the major adverse event (over 95% patients). The incidence of all grades of adverse reactions was similar between hypertensive and non-hypertensive patients (all P>0.05) except diarrhea (P=0.020).ConclusionsComplication of hypertension might confer a poor survival for advanced NSCLC patients with T2DM. Further prospective research is needed to confirm these findings.

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

Pixantrone, etoposide, bendamustine, rituximab (P[R]EBEN) as an effective salvage regimen for relapsed/refractory aggressive non-Hodgkin lymphoma-Polish Lymphoma Research Group real-life analysis.

Despite a significant improvement in treatment outcomes, 30-40% of aggressive non-Hodgkin lymphomas (NHL) patients are refractory or relapse after the first line therapy. Half of them are not eligible to autologous stem cell transplantation (ASCT) due to failure of platinum-based salvage regimens. Pixantrone is conditionally approved in Europe in patients with R/R aggressive NHL failing at least 2 previous lines of therapy. Polish Lymphoma Research Group (PLRG) evaluated the efficacy and tolerability of P[R]EBEN combining pixantrone, etoposide, bendamustine with or without rituximab), a new regimen developed recently by Francesco d'Amore, in real-life experience. In this retrospective audit, we analyzed the data of consecutive 25 R/R NHL cases, treated with P[R]EBEN regimen in 9 PLRG centers. Safety and efficacy data, including adverse reactions (AE), response rates, progression-free and overall survival (PFS and OS) were collected. Overall response rate (ORR) to P[R]EBEN regimen was 68% (40% CR and 28% PR). Most patients responded, relatively early, by second cycle of therapy. P[R]EBEN was effective in 8 out of 15 patients (53%) refractory to previous platinum-based salvage regimens. In 4 patients (16%) stabilization of disease (SD) during therapy was observed and further 4 patients (16%) progressed during the treatment (PD). Response rates were higher in patients, chemosensitive to their prior regimen (ORR - 87.5%, including 50% CR). At the median follow-up of 7.5 months (range 1-16) the median PFS and OS were not reached. Projected PFS and OS at 12 months are 68% and 78% respectively. The P[R]EBEN regimen was well tolerated and most of patients received it as out-patients. AEs grade ≥3 occurred in 17 patients (68%). Most common grade 3-4 AEs were due to hematological toxicity with febrile neutropenia observed in 5 patients (20%). There were no episodes of septic deaths. Six patients (24%) died during treatment and follow-up period, all of them due to lymphoma progression. Our data suggest good efficiency and tolerability of P[R]EBEN regimen as a rescue therapy in patients with R/R aggressive NHL.

Efficacy and safety analysis of VCD and VD regimens for treatment of newly diagnosed patients with multiple myeloma

Objective To compare the clinical efficacy and safety of bortezomib, cyclophosphamide, dexamethasone (VCD) regimen and bortezomib dexamethasone (VD) regimen in the treatment of the patients with newly diagnosed multiple myeloma (NDMM). Methods The clinical data of 73 patients with NDMM in Shanxi Dayi Hospital from January 2013 to January 2016 were retrospectively analyzed. According to the chemotherapy regimen, the patients were divided into VCD group (41 cases) and VD group (32 cases). The efficacy and adverse reactions of the two groups were evaluated. Results The overall response rate of VCD group and VD group was 80.5% (33/41) and 78.1% (25/32) respectively, and the difference was not statistically significant (χ2= 0.061, P= 0.804); and complete remission (CR) rate was 36.6% (15/41) and 15.6% (5/32) respectively, and the difference was statistically significant (χ2= 3.970, P= 0.046); the median progression-free survival (PFS) was 27 months and 24 months respectively, and the median overall survival (OS) was 35 months and 33 months respectively, and the differences were not statistically significant (all P > 0.05). Most adverse reactions occurred in grade 1-2, in which peripheral polyneuropathy and thrombocytopenia were the most common. Peripheral neuritis was the most common finding among the adverse reactions of grade 3. The incidence of adverse reactions in both groups was not statistically significant (P > 0.05). Conclusions VCD and VD regimen could be recommended as a better induction therapy for NDMM patients. Compared with VD scheme, VCD scheme has a higher CR rate. Key words: Multiple myeloma; Therapy; Adverse events

Comparison of the clinical efficacy of icotinib and gefitinib in the treatment of stage IV lung adenocarcinoma patients with EGFR sensitive gene mutation

Objective To compare the clinical efficacy of icotinib and gefitinib in the treatment of advanced(stage Ⅳ) lung adenocarcinoma patients with epidermal growth factor receptor(EGFR) sensitive gene mutation. Methods Fifty-four advanced(stage Ⅳ) lung adenocarcinoma patients with EGFR sensitive gene mutation were selected.According to the random number table method, the patients were divided into two groups, with 27 cases in each group.The icotinib group received icotinib hydrochloride targeted therapy, and the gefitinib group was orally given gefitinib.The clinical efficacy, quality of life score, adverse reactions, progression free survival(PFS) were compared between the two groups. Results There were no statistically significant differences in clinical curative effect between the two groups[complete remission(0 cases vs.0 cases), partial remission(9 cases vs.8 cases), stable(12 cases vs.14 cases), progress disease(6 cases vs.5 cases), objective response rate(33.3% vs.29.6%), disease control rate(77.8% vs.81.5%), Z=1.060, χ2=0.143, 0.100, all P>0.05]. After treatment, the differences of body function, social function, psychological function, common symptoms and side effects, specific modules in the gefitinib group were not statistically significant compared with those before treatment(t=1.402, 1.199, 1.840, 1.860, 1.275, all P>0.05). The icitinib group had better body function, psychological function, common symptoms, side effects and specific modules than before treatment(t=2.525, 3.335, 4.477, 3.778, all P 0.05). The incidence rate of Ⅲ-Ⅳ grade adverse reactions of the icotinib group was 7.4%, which was lower than 25.9% of the gefitinib group(χ2=9.000, P 0.05). The average PFS of the icotinib group under EGFR gene 21L858R mutation was (14.62±3.85)months, which was longer than (10.73±5.61)months of the gefitinib group(t=2.971, P<0.05). Conclusion Icotinib, gefitinib in the treatment of advanced(stage Ⅳ) lung adenocarcinoma patients with EGFR sensitive gene mutation has similar clinical effect, but icotinib has higher safety, better tolerability, and can significantly improve the quality of life of patients, prolong the EGFR mutation of the 21L858R gene under the survival of patients. Key words: Carcinoma, non-small-cell lung; Adenocarcinoma; Genes; Mutation; Icotinib; Gefitinib

Efficacy of intensive radiotherapy combined with mesylate apatinib for treatment of elderly patients with locally advanced cardia cancer and its effect on vascular endothelial growth factor receptor

Objective To observe the clinical effect of intensity modulated radiation therapy (IMRT) combined with apapatinib mesylate in the treatment of elderly patients with locally advanced cardia adenocarcinoma and its effect on vascular endothelial growth factor receptor (VEGFR). Methods Forty-six elderly patients with locally advanced cardia cancer who were unwilling to accept surgery or couldn't get complete removal of cancers in Xuzhou Hospital Affiliated to Jiangsu University between January 2015 and April 2016 were collected. All the patients were randomly divided into the control group (23 cases) and the observation group (23 cases) according to the random number table method. The control group received radiotherapy alone. In the observation group, oral apatinib (500 mg/d) was taken in the first day of radiotherapy after breakfast until the disease progress or death occurred. Results The total effective rate was 92% (19/23) in the observation group and 60% (10/23) in the control group. There was a significant difference between the two groups (χ2= 5.86, P 0.05). Hypertension, proteinuria and rash response in the observation group were increased compared with the control group, but no Ⅳ grade of adverse reactions occurred. The median progression-free survival time was 10 months in the observation group and 8 months in the control group respectively (P= 0.01). Conclusion IMRT combined with apatinib in the treatment of elderly patients with locally advanced gastric cardia has a favorable efficacy and tolerance. Key words: Cardia neoplasms; Radiotherapy, intensity-modulated; Vascular endothelial growth factors

A phase II prospective study on raltitrexed combined with concurrent radiotherapy for elderly esophageal carcinoma

Objective To evaluate the clinical effects and adverse reaction of raltitrexed combined with radiation for esophageal carcinoma in elderly patients. Methods Sixty patients were randomly divided into two groups by the envelope method, 30 patients in experimental group received raltitrexed combined with radiotherapy and 30 patients in control group received radiotherapy only. Patients in both groups received conventional radiotherapy with a total dose of 56-60 Gy/28-30 F. In experimental group, raltitrexed 2.6 mg/m2 was administered concurrently with the radiotherapy on d1 and d22. Two cycles of concurrent chemotherapy were administered during radiotherapy. The short-term effects, survival times and adverse reactions of the two groups were compared. Results The total effective rates of experimental group and control group were 93.3% and 73.3%, respectively, and there was statistically significant difference between the two groups (χ2=4.320, P=0.038). The median survival times of experimental group and control group was 24.0 months and 12.0 months, respectively, and there was statistically significant difference by Log-rank test (χ2=6.048, P=0.014). The major adverse reactions of grade 3-4 in experimental group and control group were radiation-induced esophagitis (10.0% vs. 3.3%; χ2=0.268, P=0.605), leukopenia (13.3% vs. 10.0%; χ2=0.000, P=1.000), thrombocytopenia (3.3% vs. 0; P=1.000), nausea and vomiting (6.7% vs.0; χ2=0.517, P=0.472), and the differences were not statistically significant. Conclusion Raltitrexed combined with radiotherapy can enhance the short-term effect and prolong the survival time for the elderly esophageal carcinoma patients, and the adverse reactions are mild. It is worthy of further clinical study. Key words: Esophageal neoplasms; Radiotherapy; Drug therapy; Radiation tolerance; Raltitrexed