Investigation of Factors Affecting the Success Rate of Third-Line Therapy against Helicobacter pylori Infection / 医薬品情報学

Objective: The success rate of third-line treatment for Helicobacter pylori (H. pylori) infection has been reported to depend on the use of antibacterial agents, potassium-competitive acid blockers, and proton pump inhibitors. However, there is insufficient information on the success rate of H. pylori treatment due to the differences in the clinically used drugs. Here, the factors influencing the success rate of third-line treatment for H. pylori infection was investigated.Methods: Patients aged 20 years or older, who had received third-line treatment for H. pylori infection from January 2013 to December 2021 at the Kameda Medical Center were included. The exclusion criteria were as follows: patients with unknown treatment results and discontinuation of treatment. The primary endpoint was treatment success rate, based on the differences in the treatment regimen and drug choice, which was retroactively investigated from medical records. Confounding factors were adjusted by multivariate logistic regression analysis.Results: Treatment regimens containing sitafloxacin resulted in higher treatment success rates (p<0.05). Multivariate logistic regression analysis showed that the administration of sitafloxacin was the only statistically significant factor influencing treatment success. However, vonoprazan also tended to influence treatment success.Conclusion: Treatment with sitafloxacin and vonoprazan increases the success rate of third-line treatment against H. pylori infection.

Efficacy of Combination of Camrelizumab with Anlotinib as Third-line Therapy for Patients with Advanced Non-small Cell Lung Cancer / 肿瘤防治研究

Objective To investigate the clinical efficacy and related adverse reactions of the combination of camrelizumab with anlotinib as the third-line therapy on advanced non-small cell lung cancer. Methods We retrospectively analyzed the clinical data of 84 patients with advanced non-small cell lung cancer after second-line treatment. According to different treatment methods, 44 patients who received camrelizumab combined with anlotinib were included in the observation group, and 40 patients who received anlotinib alone were included in the control group. The PFS, ORR, DCR and incidence of adverse reactions were analyzed and compared between the two groups. Results The median PFS of the observation group was longer than that of the control group (7.0 vs. 5.6 months, P=0.001). No statistically significant difference was observed in ORR, DCR, the incidence of adverse reactions or the incidence of adverse reactions above grade 3 between two groups (all P > 0.05). Conclusion The clinical efficacy of camrelizumab combined with anlotinib as third-line therapy on advanced non-small cell lung cancer is better than anlotinib alone, and the safety is good.

Analysis of the Curative Effect and Influencing Factors of Nilotinib Second-line and Dasatinib Third-line on Chronic Myelogenous Leukemia Failed First-line and Second-line Treatment / 中国实验血液学杂志

OBJECTIVE@#To evaluate the efficacy of the second-line nilotinib and third-line dasatinib on chronic myelogenous leukemia (CML) with failed first- and second-line treatments, and analyze the influencing factors of the efficacy.@*METHODS@#Selected 83 patients in The Third People's Hospital of Kunshan City, Jiangsu Province with CML who were treated with nilotinib as the second-line treatment after the failure of the first-line treatment with imatinib as the second-line treatment group (referred to as the second-line group) from January 2014 to December 2018, and 61 CML patients who were treated by dasatinib as the third-line treatment group (referred to as the third-line group) after the failure of the second-line treatment with nilotinib; the first-line treatment with imatinib failed, but due to various reasons, the patients were fully after being informed of the possible serious consequences of not changing the drug treatment, 37 CML patients who were still required to continue imatinib treatment served as the control group. The hematological, genetic and molecular responses of each group were compared for 3, 6, and 24 months of treatment. LogistiC regression was used to analyze the factors affecting the second and third line curative effects.@*RESULTS@#The three groups had statistically significant differences in the rates of achieving CHR, MCyR, and MMR at 3, 6, and 12 months of treatment (P<0.05). Compared the two groups, the CHR rates of the second-line group at 3, 6, and 12 months of treatment were 100.00%, 97.59%, and 95.18%, respectively; higher than the third-line group's 90.16%, 86.89%, 83.61% and the control group's 83.78%, 75.68% and 72.97%; the CHR rate of the third-line group was higher than that of the control group at 6 and 12 months of treatment. The rates of reaching MCyR at 3, 6, and 12 months after treatment in the second-line group were 87.95%, 93.98% and 93.98%, respectively, while those in the third-line group were 80.33%, 88.52% and 86.89%, which were higher than those of the control group of 67.57%, 64.86% and 48.65%. The rates of achieving MMR at 3, 6, and 12 months of treatment in the second-line group were 19.28%, 33.72% and 60.24%, respectively, and those in the third-line group were 11.48%, 26.23% and 49.18%, which were higher than those of the control group of 0.00%, 2.70% and 0.00%; The rate of reaching MMR within 12 months of treatment in the second-line group was higher than that of the third-line group, and the differences was statistically significant (P<0.05). There was no significant difference in the rate of reaching MCyR between the second-line group and the third-line group at 3, 6, and 12 months, and the rate of reaching MMR at 3 and 6 months (P>0.05). The incidence of nausea and vomiting among the three main non-hematological adverse reactions, and the incidence of grade 1~2 anemia among the hematological adverse reactions were statistically significant (P<0.05). There was no significant difference in the incidence of rash, eyelid edema, diarrhea, thrombocytopenia, leukopenia and neutropenia in the three groups (P>0.05). The incidence of nausea and vomiting and grade 1~2 anemia in the second-line group and the third-line group were higher than that of the control group, and the difference was statistically significant (P<0.05). There were statistically significant differences in Sokal score, medication compliance, and hematological adverse reactions between the MMR group and the non-MMR group (P<0.05). Logistic regression analysis showed that dose reduction or withdrawal during the treatment period, and grade 3~4 hematological adverse reactions were the main factors affecting the second and third line curative effects (OR=22.160, 2.715, 95% CI=2.795-93.027, 1.882-48.834).@*CONCLUSION@#The second-line nilotinib and the third-line dasatinib have a better effect on CML patients who have failed the first and second-line treatments. Grade 3~4 hematological adverse reactions, dose reduction or withdrawal are risk factors that affect the efficacy of second and third-line treatments.

Advances in colorectal cancer research from 2017 annual meeting of Chinese Society of Clinical Oncology / 中华消化外科杂志

There are several progresses in colorectal cancer research from 2017 annual meeting of Chinese Society of Clinical Oncology (CSCO).(1) Phase Ⅲ multi-center trial FRESCO and TERRA study have showed domestic new drug Fruquintinib and Japanese oral combination anti-cancer drug TAS-102 significantly improved overall survival (OS) comparing to placebo in third-line metastatic colorectal cancer (mCRC) patients.(2) Preoperative neoadjuvant chemotherapy with mFOLFOXIRI and selective radiotherapy or concomitant boost neoadjuvant chemoradiotherapy (nCRT) followed by one cycle of XELOX,can improve short-term outcome for locally advanced rectal cancer,and clinical and pathological features can be used to predict complete response following nCRT.(3) In asymptomatic elderly population,the specificity of septin9 methylation detection in plasma cfDNA as colorectal cancer screening is low,but the probability of negative predictions as non-colorectal cancer is high.And integrated signature of the gut microbiome and metabolome serves as diagnostic biomarkers in patients with colorectal cancer.(4) Immunoscore system predicts prognosis after liver metastasectomy in colorectal metastases,and the immune signature difference between right and left colon cancer could explain the difference of targeted therapy.

A pilot study of gemcitabine and paclitaxel as third-line chemotherapy in metastatic urothelial carcinoma / Journal of Rural Medicine

<p><b>Background:</b> We evaluated the effectiveness of gemcitabine and paclitaxel therapy in patients with metastatic urothelial carcinoma for whom two lines of sequential chemotherapy had been unsuccessful.</p><p><b>Methods:</b> A total number of 105 patients who had previously received first-line chemotherapy consisting of gemcitabine and cisplatin or carboplatin, were treated with second-line gemcitabine and docetaxel therapy between June 2006 and May 2015. Of these patients, 15 with an Eastern Cooperative Oncology Group Performance Status of 0 or 1 were administered gemcitabine and paclitaxel as third-line treatment from 2013 after failure of the second-line therapy. For each 21-day cycle, gemcitabine (1000 mg/m²) was administered on days 1, 8, and 15, and paclitaxel (200 mg/m²) on day 1. Patients were assessed for each cycle and any adverse events were noted. Furthermore, a Short Form Health Survey questionnaire was used to assess each patient’s quality of life.</p><p><b>Results:</b> Third-line gemcitabine and paclitaxel treatment cycles were undertaken for a median of four times (range 2–9). The disease control rate was 80.0%. After second-line gemcitabine and docetaxel therapy was completed, median progression-free survival and median overall survival were determined as 9.8 and 13.0 months, respectively. The only prognostic factor for overall survival, as determined by univariate and multivariate analyses, was third-line gemcitabine and paclitaxel therapy. Neutropenia (66.7%) and thrombocytopenia (53.3%) were noted as the grade 3 treatment-related toxicities. After two cycles of third-line gemcitabine and paclitaxel therapy, the pre- and post-treatment quality of life scores did not differ significantly.</p><p><b>Conclusions:</b> Results demonstrate that third-line combination therapy using gemcitabine and paclitaxel is a feasible option for metastatic urothelial carcinoma patients.</p>

Efficacy of Levofloxacin-Based Third-Line Therapy for the Eradication of Helicobacter pylori in Peptic Ulcer Disease

BACKGROUND/AIMS: The resistance rate of Helicobacter pylori is gradually increasing. We aimed to evaluate the efficacy of levofloxacin-based third-line H. pylori eradication in peptic ulcer disease. METHODS: Between 2002 and 2014, 110 patients in 14 medical centers received levofloxacin-based third-line H. pylori eradication therapy for peptic ulcer disease. Of these, 88 were included in the study; 21 were excluded because of lack of follow-up and one was excluded for poor compliance. Their eradication rates, treatment regimens and durations, and types of peptic ulcers were analyzed. RESULTS: The overall eradiation rate was 71.6%. The adherence rate was 80.0%. All except one received a proton-pump inhibitor, amoxicillin, and levofloxacin. One received a proton-pump inhibitor, amoxicillin, levofloxacin, and clarithromycin, and the eradication was successful. Thirty-one were administered the therapy for 7 days, 25 for 10 days, and 32 for 14 days. No significant differences were observed in the eradication rates between the three groups (7-days, 80.6% vs 10-days, 64.0% vs 14-days, 68.8%, p=0.353). Additionally, no differences were found in the eradiation rates according to the type of peptic ulcer (gastric ulcer, 73.2% vs duodenal/gastroduodenal ulcer, 68.8%, p=0.655). CONCLUSIONS: Levofloxacin-based third-line H. pylori eradication showed efficacy similar to that of previously reported first/second-line therapies.

Treatment with dasatinib or nilotinib in chronic myeloid leukemia patients who failed to respond to two previously administered tyrosine kinase inhibitors - a single center experience

OBJECTIVE: To evaluate hematological, cytogenetic and molecular responses as well as the overall, progression-free and event-free survivals of chronic myeloid leukemia patients treated with a third tyrosine kinase inhibitor after failing to respond to imatinib and nilotinib/dasatinib. METHODS: Bone marrow karyotyping and real-time quantitative polymerase chain reaction were performed at baseline and at 3, 6, 12 and 18 months after the initiation of treatment with a third tyrosine kinase inhibitor. Hematologic, cytogenetic and molecular responses were defined according to the European LeukemiaNet recommendations. BCR-ABL1 mutations were analyzed by Sanger sequencing. RESULTS: We evaluated 25 chronic myeloid leukemia patients who had been previously treated with imatinib and a second tyrosine kinase inhibitor. Nine patients were switched to dasatinib, and 16 patients were switched to nilotinib as a third-line therapy. Of the chronic phase patients (n=18), 89% achieved a complete hematologic response, 13% achieved a complete cytogenetic response and 24% achieved a major molecular response. The following BCR-ABL1 mutations were detected in 6/14 (43%) chronic phase patients: E255V, Y253H, M244V, F317L (2) and F359V. M351T mutation was found in one patient in the accelerated phase of the disease. The five-year overall, progression-free and event-free survivals were 86, 54 and 22% (p<0.0001), respectively, for chronic phase patients and 66%, 66% and 0% (p<0.0001), respectively, for accelerated phase patients. All blast crisis patients died within 6 months of treatment. Fifty-six percent of the chronic phase patients lost their hematologic response within a median of 23 months. CONCLUSIONS: Although the responses achieved by the third tyrosine kinase inhibitor were not sustainable, a third tyrosine kinase inhibitor may be an option for improving patient status until a donor becomes available for transplant. Because the long-term outcome ...

Recent Update on Third-line Helicobacter pylori Eradication

The eradication rate of Helicobacter pylori has been decreasing progressively, primarily due to increased resistance to antibiotics. The widely used standard clarithromycin-based triple therapy regimen is no longer achieving eradication rate of 80% in intent-to-treat analysis in many countries. Due to the primary and secondary resistance to metronidazole, the key antibiotic for second line regimen, eradication rate of standard metronidazole based quadruple therapy is also decreasing. It is rational to check antibiotic resistance for selecting regimens in third-line rescue eradication therapy, but it requires time and resource. Limited studies regarding the efficacy of a dual regimen consisting of high dose proton pump inhibitor and amoxicillin showed controversial results. Efficacy of rescue regimens containing fluoroquinolones, such as levofloxacin and moxifloxacin, were reported to be insufficient due to increasing incidence of primary and secondary resistance. Eradication result of third-line rescue regimens with sitafloxacin, a novel quinolone of which the antibacterial activity towards H. pylori is more than 100-fold that of ciprofloxacin in vitro, is promising. Although prevalence of serious side effect such as myelotoxicity with rifabutin-based rescue regimen is reported to be lower than expected, wider use of rifabutin is still concerned regarding the emergence of resistant mycobacterial species. Rifaximin based rescue regimen is safer and cheaper than rifabuitin based regimen. However, further investigation for better eradication rates by enhancing higher drug concentration in the gastric mucus layer needs to be evaluated.

The Efficacy and Safety of Platinum/Vinorelbine as More Than Second-Line Chemotherapy for Advanced Non-small Cell Lung Cancer / Journal of the Korean Cancer Association, 대한암학회지

PURPOSE: There is no regimen that is strongly recommended for more than second-line treatment. We investigated the efficacy and safety of platinum/vinorelbine as more than second-line treatment. MATERIALS AND METHODS: We selected patients with advanced non-small cell lung cancer (NSCLC) who received treatment with platinum/vinorelbine at Chungnam National University Hospital from August 2001 to December 2013. The primary end point was the response rate, and secondary end points were progression-free survival (PFS), overall survival (OS), and toxicity. RESULTS: Thirty-five patients were enrolled. Response rate was 22.9% (complete response, 0 patients [0%]; partial response, eight patients [22.9%]; stable disease, 10 patients [28.6%]; progressive disease, 14 patients [40.0%]). A significantly higher response rate was observed for patients who had responded to previous chemotherapy than for those who did not (34.8% [8/23] vs. 0% [0/12], p=0.020). The median PFS was 4 months (range, 1 to 21 months). Patients with adenocarcinoma and non-smokers had a significantly longer PFS than patients with non-adenocarcinoma and smokers (5 months vs. 2 months, p=0.007; 4.5 months vs. 2 months, p=0.046, respectively). The median OS was 10 months (range, 1 to 41 months). Patients with good performance status and non-smokers had a significantly longer OS than patients with poor performance status and smokers (14 months vs. 4 months, p=0.02; 18.5 months vs. 6 months, p=0.049, respectively). The main serious adverse event (grade 3 or 4) was neutropenia (15 events, 13.3%) in a total of 113 cycles. CONCLUSION: Platinum/vinorelbine was effective as more than second-line chemotherapy, and the toxicity was tolerable, in patients with advanced NSCLC.

The efficacy and safety of albumin-bound paclitaxel in more than the third-line chemotherapy for advanced malignance / 肿瘤研究与临床

Objective To observe the efficacy and safety of albumin-bound paclitaxel on the patients with advanced malignance in more than the third-lines (including the third-lines).Methods 34 patients with advanced malignance diagnosed by pathological evidence accepted more than the third-lines (including the third-lines) chemotherapy containing albumin-bound paclitaxel after failure of chemotherapy.The efficacy and safety were observed.Results Totally 110 cycles chemotherapy were completed,with a mean of 3.24 cycles in each of the 34 patients.No CR patients,12 cases of PR,9 cases of SD and 13 cases of PD were found.The response rate (RR) was 35.29 ％ (12/34) and the disease control rate (DCR) was 61.76 ％ (21/34).The main toxicity was hematologic toxicity,including neutropenia in 26 cases (76.47 ％),anemia in 14 cases (41.18 ％) and thrombocytopenia in 3 cases (8.82 ％).Other common adverse reactions included alopecia in 27 patients (79.41％) and muscle and joint pain in 15 cases (44.18 ％).Conclusions The albumin-bound paclitaxel is effective and tolerable in patients with advanced malignance in more than the third-lines (include the thirdlines) chemotherapy.

Comparison of Rifabutin- and Levofloxacin-based Third-line Rescue Therapies for Helicobacter pylori / 대한소화기학회지

BACKGROUND/AIMS: There is increasing need for third-line therapy of Helicobacter pylori due to increasing level of antibiotics resistance. The aim of this study was to compare rifabutin and levofloxacin rescue regimens in patients with first- and second-line Helicobacter pylori eradication failures. METHODS: Patients, in whom a first treatment with proton pump inhibitor-clarithromycin-amoxicillin and a second trial with proton pump inhibitor-bismuth-tetracycline-metronidazole had failed, received treatment with either rifabutin or levofloxacin, plus amoxicillin (1 g twice daily) and standard dose proton pump inhibitor. Eradication rates were confirmed with 13C-urea breath test or rapid urease test 4 weeks after the cessation of therapy. RESULTS: Eradication rates were 71.4% in the rifabutin group, and 57.1% in the levofloxacin group, respectively. Although there was no significant difference in Helicobacter pylori eradication rates between two groups (p=0.656), rifabutin based regimen showed relatively higher eradication rate. CONCLUSIONS: Helicobacter pylori eradication rates of rifabutin- or levofloxacin-based triple therapy could not achieve enough eradication rate. Further studies would be needed on combination of levofloxacin and rifabutin-based regimen or culture based treatment.