Preliminary analysis of immunotherapy combined with second-line treatment for esophageal squamous cell carcinoma patients / 中华放射肿瘤学杂志

Objective:To investigate the efficacy of camrelizumab combined with second-line therapy in patients with recurrent or metastatic esophageal squamous cell carcinoma (ESCC) in the real-world settings.Methods:Clinical data of 48 patients with esophageal cancer who met the inclusion criteria were retrospectively analyzed. The types of failure after first-line treatment, clinical efficacy, side effects and prognostic factors of second-line treatment were analyzed. SPSS 25.0 software was used for statistical analysis. Count data were expressed by composition ratio and analyzed by Chi-square test or Fisher's exact test. Survival analysis was conducted by Kaplan-Meier curve and log-rank test. Non-normally distributed data were recorded with the median, range and quartile. Results:There were 26, 14, and 4 cases of combined chemoradiotherapy, chemotherapy and radiotherapy in the treatment of second-line camrelizumab, and 4 cases received immunotherapy alone. The median duration of immunotherapy was 6 cycles (range, 2-39 cycles). After second-line treatment, the short-term efficacy of 17, 27 and 4 cases was partial remission (PR), stable disease (SD) and progressive disease (PD), respectively. The overall response rate (ORR) was 35.4% and disease control rate (DCR) was 91.7%. The 1- and 2-year OS rates were 42.9% and 22.5%, and 1- and 2-year PFS rates were 29.0% and 5.8%. The median OS and PFS were 9.0 months (95% CI=6.4-11.7) and 8.5 months (95% CI=1.5-5.6), respectively. Multivariate analysis showed that combined immunotherapy mode, number of cycles of immunotherapy and short-term efficacy were the independent prognostic indicators affecting OS in this group of patients ( HR=2.598, 0.222, 8.330, P=0.044, <0.001, <0.001). Lymphocyte count, neutrophil-lymphocyte ratio (NLR), platelet-lymphocyte ratio (PLR), combined immunotherapy mode and short-term efficacy were the independent prognostic indicators affecting PFS in this group ( HR=3.704, 3.598, 6.855, 2.159, 2.747, P=0.009, 0.008, <0.001, 0.049, 0.012). Conclusions:Camrelizumab combined with second-line therapy can bring survival benefit to patients with recurrent or metastatic ESCC after first-line therapy, especially immunotherapy combined with chemoradiotherapy can significantly provide survival benefit. Peripheral blood inflammatory biomarkers are independent indicators affecting clinical prognosis of patients. Patients with better short-term efficacy also achieve better prognosis. The final conclusion remains to be validated by a large number of randomized controlled studies.

Levofloxacin-based triple therapy versus bismuth-based quadruple therapy in the treatment of Helicobacter pylori as the rescue therapy: a meta analysis / 中华内科杂志

Objective To evaluate the efficacy of levofloxacin-based triple therapy and bismuthbased quadruple therapy in the treatment of Helicobacter pylori (Hp) infection as rescue regimens.Methods Related randomized controlled trials assessing the efficacy and safety of levofloxacin-based triple therapy eradicating Hp as salvage treatment were retrieved from Pubmed,Cochrane Library,SPRINGER,VIP database,WanFang database and CKNI database.The literature quality was evaluated by the improved Jadad criterion.RevMan5.3 sofeware was applied to data analysis.The mergment model was chosen on the basis of the outcome of the heterogeneity tests and original data was pooled for meta-analysis.Publication bias assessed with funnel plots.Results Ultimately seventeen literatures were included for meta-analysis,the analysis showed that the eradication rate of levofloxacin-based triple therapy was higher comparing to the bismuth-based quadruple therapy but the difference was not statistically significant (77.0％ vs 68.7％,OR =1.52,95％ CI 0.96-2.42,P =0.34).In European countries,levofloxacin-based triple therapy was more effective than quadruple therapy(80.6％ vs 68.5％,OR =2.18,95％ CI 1.25-3.81,P ＜ 0.05),while eradication rates of two groups in Asian countries were similar.The 7-day levofloxacin-based triple therapy and quadruple therapy showed comparable efficacy,whereas the 10-day levofloxacin-based triple therapy was significantly more effective than quadruple therapy (87.7％ vs 61.3％,OR =4.92,95％ CI 3.09-7.82,P ＜ 0.05).The efficacy was not influenced by the dose of levofloxacin.The adverse effects were significantly lesser(19.1％ vs 29.5％,OR =0.47,95％ CI 0.26-0.82,P ＜ 0.05),whereas the compliance rate was significantly higher in levofloxacin group (96.0％ vs 89.9％,OR =2.27,95％ CI 1.33-3.87,P ＜ 0.05).Conclusions Comparing with bismuth-based quadruple therapy,levofloxacinbased triple therapy has higher eradication rate,compliance rate and lesser side effects,so we recommend it as a second-line rescue therapy after front-line Hp eradication failure.The optimal second-line alternative scheme might differ among countries depending on quinolone resistance.

The efficacy and safety of pemetrexed and nedaplatin in salvage chemotherapy of advanced urinary carcinoma / 中华泌尿外科杂志

Objective To evaluate the efficacy and toxicity of pemetrexed and nedaplatin in the treatment of patients with locally advanced or metastatic urothelial cell carcinoma who failed a first-line GC regimen.Methods A total of 11 patients with locally advanced or metastatic urothelial carcinoma failed with first-line treatment of GC regimen were included in the present study.There were 6 males and 5 females,aged 56-80 years old,median age was 65 years old.Six patients' primary tumors were in bladder,4 in the renal pelvis,1 ureter.There were 7 cases with ECOG score 0 point,3 cases 1 point,1 case 2 points.Patients received pemetrexed 500 mg/m2 intravenously on the 1st day,and nedaplatin 25mg/m2 from the 1st to 3th day every 21 days.The evaluation of efficacy and adverse reactions were carried out after 2 to 3 cycles.Results Eleven patients received 1 to 6 cycles (mean 3.3 cycles) treatments.There were 2 cases (18.2％) complete remission,5 cases (45.5％) partial remission,2 cases (18.2％) no change and 2 cases (18.2％) progressed.The total effective rate was 63.6％.The main adverse events were anemia (6 cases),leukopenia (5 cases),nausea and vomiting (6 cases) and rash (5 cases),all of which were mild to moderate.No treatment-related death occurred.Conclusions Pemetrexed and nedaplatin regimen could be effective in the treatment of advanced urothelial carcinoma after first-line chemotherapy failed.The side effect is mild.

Analysis of efficacy of pemetrexed or fluorouracil combined with irinotecan in the treatment of advanced colorectal cancer / 中国生化药物杂志

Objective To study the efficacy of pemetrexed or fluorouracil in combination with irinotecan in the treatment of advanced colorectal cancer. Methods 68 patients with advanced colorectal cancer were selected from January 2014 to January 2016 in Qinghai Provincial People's hospital. Patients were divided into the control group and the observation group by random grouping, and 34 patients for each group. Patients in the control group were received second-line therapy with fluorouracil and irinotecan. The patients in the observation group were received second-line therapy with the combination of pemetrexed and irinotecan. After treatment, the treatment effects, adverse reactions and living conditions of two groups were compared. Results The total effective rate of the observation group was 38.24%, was higher than that of the control group 8.82% (P<0.05); the observation group's disease control rate was 76.47%, was higher than that of the control group 52.94% (P<0.05). The incidence of adverse reactions in the observation group was 200.00%, which was lower than 305.88% in the control group (P<0.05). Progression free survival time in the observation groupwas (6.81±2.31) months, was higher than the control group (3.75±1.06) months (P<0.05); the total survival time in the observation group was (14.69±4.28) month, was higher than the control group (8.76±2.27) month (P<0.05). Conclusion In the second-line treatment of advanced colorectal cancer, the application of raltitrexed combined with irinotecan treatment, could improve the total efficiency of treatment and disease control rate, reduce adverse reactions, and prolong the survival time of patients.

Analysis of efficacy of pemetrexed or fluorouracil combined with irinotecan in the treatment of advanced colorectal cancer / 中国生化药物杂志

Objective To study the efficacy of pemetrexed or fluorouracil in combination with irinotecan in the treatment of advanced colorectal cancer. Methods 68 patients with advanced colorectal cancer were selected from January 2014 to January 2016 in Qinghai Provincial People's hospital. Patients were divided into the control group and the observation group by random grouping, and 34 patients for each group. Patients in the control group were received second-line therapy with fluorouracil and irinotecan. The patients in the observation group were received second-line therapy with the combination of pemetrexed and irinotecan. After treatment, the treatment effects, adverse reactions and living conditions of two groups were compared. Results The total effective rate of the observation group was 38.24%, was higher than that of the control group 8.82% (P<0.05); the observation group's disease control rate was 76.47%, was higher than that of the control group 52.94% (P<0.05). The incidence of adverse reactions in the observation group was 200.00%, which was lower than 305.88% in the control group (P<0.05). Progression free survival time in the observation groupwas (6.81±2.31) months, was higher than the control group (3.75±1.06) months (P<0.05); the total survival time in the observation group was (14.69±4.28) month, was higher than the control group (8.76±2.27) month (P<0.05). Conclusion In the second-line treatment of advanced colorectal cancer, the application of raltitrexed combined with irinotecan treatment, could improve the total efficiency of treatment and disease control rate, reduce adverse reactions, and prolong the survival time of patients.

Advances in personalized treatment of small cell lung cancer / 中国肿瘤临床

Small cell lung cancer (SCLC) is a lethal malignancy characterized by rapid growth, early metastatic spread, and unfavorable survival outcomes. Optimizing treatment for patients with SCLC has been the focus for investigators. The emergence of precision medi-cine and personalized treatment brought significant breakthroughs into SCLC treatment and changed the therapeutic model. The de-velopment of molecular bioinformatics increased our understanding of complex molecular mechanisms of SCLC, and novel targets for personalized treatment have been developed. Clinical trials testing these targets are ongoing, which show the potential of personal-ized treatment for SCLC.

Advances in chemotherapy of small cell lung cancer / 中国肿瘤临床

Small cell lung cancer (SCLC) accounts for about 13%of lung cancer. SCLC exhibits an early metastatic potential and sensitivi-ty to first-line cytotoxic chemotherapy compared with non-small cell lung cancer. Current treatments include surgery, radiotherapy, and chemotherapy. Platinum plus etoposide is viewed as the standard first-line chemotherapy. However, recurrence rate of cancer af-ter platinum plus etoposide chemotherapy is high. Topotecan monotherapy is the standard second-line chemotherapy. Meanwhile, novel targeted immunotherapy showed poor effects. Hence, new breakthroughs in the treatment of SCLC are urgently needed.

Efficacy of 7-Day and 14-Day Bismuth-Containing Quadruple Therapy and 7-Day and 14-Day Moxifloxacin-Based Triple Therapy as Second-Line Eradication for Helicobacter pylori Infection

BACKGROUND/AIMS: Bismuth-containing quadruple and moxifloxacin-based triple regimens are recommended as second-line therapy for Helicobacter pylori infection. The aim of this study was to compare the efficacy of each regimen. METHODS: From August 2004 to October 2012, a total of 949 patients (mean age, 54.32+/-12.08 years; male, 49.4%) who failed H. pylori eradication with a standard triple regimen were included. Patients treated with a bismuth-containing quadruple regimen for 7 and 14 days were designated as 7-BMT and 14-BMT, respectively, and those treated with a moxifloxacin-based triple regimen for 7 and 14 days were designated as 7-MA and 14-MA, respectively. H. pylori eradication was confirmed using the 13C-urea breath test, rapid urease test or histology. RESULTS: The eradication rates by 7-BMT, 14-BMT, 7-MA, and 14-MA were 66.4% (290/437), 71.1% (113/159), 53.1% (51/96), and 73.5% (189/257), respectively, by intention-to-treat analysis (ITT) and 76.5% (284/371), 83.8% (109/130), 55.6% (50/90), and 80.6% (187/232), respectively, by per-protocol analysis (PP). The eradication rates were higher in 14-BMT than 7-BMT by the ITT and PP analyses (p=0.277 and p=0.082, respectively). The 14-BMT and 14-MA treatments showed similar efficacies by ITT and PP (p=0.583 and p=0.443, respectively). CONCLUSIONS: The 7-BMT, 14-BMT, and 14-MA treatments showed similar and suboptimal efficacies. In both regimens, extending the duration of treatment may be reasonable considering the high level of antibiotic resistance in Korea.

Rescue therapies for Helicobacter pylori infection after failure of proton pump inhibitor-based standard triple therapy / 대한내과학회지

BACKGROUND/AIMS: Proton pump inhibitor (PPI)-based standard triple therapy for Helicobacter pylori infection is widely used, but it has a considerable failure rate. The aim of this study was to evaluate the efficacy and tolerability of rescue therapies with a quadruple regimen and a rifabutin-based regimen for patients who experienced failure with PPI-based standard triple therapy. METHODS: From July 2004 through October 2006, 52 patients for whom first line triple therapy (PPI, amoxicillin and clarithromycin) had failed were included in this study. They were treated with a quadruple regimen for 7 days (PPI, bismuth, tetracycline and metronidazole) as a second line therapy. For third line therapy, a rifabutin-based regimen (PPI, rifabutin and amoxicillin) was prescribed for 14 days. The H. pylori status was determined before and at least 4 weeks after therapy by the 13C urea breath test or by endoscopy with antral and corpus biopsies for a rapid urease test, histological examination and culture. RESULTS: The mean age was 52.6 years. Thirteen patients (25%) of the 52 patients were dropped. The eradication rate of the quadruple therapy was 84.6% (33/39). Three patients of the 6 failures with quadruple therapy were then treated with the rifabutin-based regimen. The eradication rate of the rifabutin-based therapy was 100% (3/3). Adverse effects (10.2%) were reported in 4 patients who were treated with quadruple regimen. CONCLUSIONS: The quadruple regimen is still an effective second-line therapy for Korean patients who experience failure with PPI-based standard triple therapy. The rifabutin-based regimen could be used as a third-line rescue therapy in Korea.

Weekly Low-Dose Docetaxel for Salvage Chemotherapy in Pretreated Elderly or Poor Performance Status Patients with Non-small Cell Lung Cancer

Although docetaxel monotherapy has shown clinical benefits for previously treated patients with advanced non-small cell lung cancer (NSCLC), the efficacy of salvage docetaxel chemotherapy for elderly patients or patients with poor performance status (PS) is controversial. Therefore, we conducted a phase II trial to evaluate the safety and efficacy of weekly low-dose docetaxel monotherapy in these patients. Forty NSCLC patients, who had been previously treated with one or more chemotherapy regimens, received docetaxel at a dose of 25 mg/m(2) weekly on days 1, 8, and 15 of a 28-day cycle. All patients were > or =65 yr or had a PS of grade 2 in the cases of <65 yr. Weekly low-dose docetaxel was well-tolerated. Grade 3/4 non-hematologic toxicities were rare; fatigue in 3 patients (8%), anorexia in 3 patients (8%) and stomatitis in 2 patients (5%). Grade 3/4 neutropenia was noted in only one patient (3%). By intent-to-treat analysis, nine patients (23%) had partial responses and eleven patients (28%) demonstrated stable disease. The median progression-free survival and overall survival were 9.9 weeks and 37.7 weeks, respectively. Weekly low-dose docetaxel therapy provides a reasonable alternative for NSCLC salvage treatment in pretreated elderly patients or in patients with a reduced PS.

Trial of Moxifloxacin-containing Triple Therapy after Initial and Second-line Treatment Failures for Helicobacter pylori Infection / 대한소화기학회지

BACKGROUND/AIMS: Proton-pump inhibitor (PPI)-based triple therapy for Helicobacter pylori eradication is widely used with considerable failure rate. Bismuth-based, second-line therapy is also associated with failures in more than 20% of cases in Korea. Our aim was to evaluate the efficacy and tolerability of third-line therapy containing moxifloxacin as a rescue in Korea. METHODS: The subjects consisted of 201 patients infected with H. pylori, who were treated with PPI-based therapy, 42 patients treated with bismuth-based after failure of initial PPI triple therapy, and 10 patients treated with moxifloxacin-containing triple therapy after failure of successive initial and second-line therapy. Eradication rate, compliance and side effect rates were compared. RESULTS: The eradication rates of initial, second-line, and third-line therapy were as follows: 67.2%/83.3%, 54.8%/76.7%, 80.0%/88.9% by intention-to-treat and per protocol analysis, respectively. The compliance of patients for each treatment was 98.2%, 90.9%, 100%, respectively. The side effect rate was significantly higher in the bismuth triple therapy than in the PPI- or moxifloxacin-containing triple therapy (p<0.05). CONCLUSIONS: Moxifloxacin-containing triple therapy shows high eradication rate with fewer side effects and good compliance. Thus, this regimen could be used as a rescue therapy.