scholarly journals Effect of Antibiotic Susceptibility and CYP3A4/5 and CYP2C19 Genotype on the Outcome of Vonoprazan-Containing Helicobacter pylori Eradication Therapy

Antibiotics ◽  
2020 ◽  
Vol 9 (10) ◽  
pp. 645
Author(s):  
Mitsushige Sugimoto ◽  
Daiki Hira ◽  
Masaki Murata ◽  
Takashi Kawai ◽  
Tomohiro Terada
Keyword(s):  
Helicobacter Pylori ◽  
Antibiotic Susceptibility ◽  
Eradication Rate ◽  
Eradication Therapy ◽  
Line Treatment ◽  
Second Line ◽  
First Line ◽  
Helicobacter Pylori Eradication ◽  
Third Line ◽  
Third Line Treatment

Background: Helicobacter pylori eradication containing the potassium-competitive acid blocker, vonoprazan, achieves a higher eradication rate than therapy with proton pump inhibitors (PPIs). Because vonoprazan is mainly metabolized by CYP3A4/5, CYP genotype may affect the eradication rate. We investigated the influence of antibiotic susceptibility and CYP3A4/5 and CYP2C19 genotypes on the eradication rates. Methods: A total of 307 Japanese who were genotyped for CYP3A4 *1/*22, CYP3A5 *1/*3 and CYP2C19 *1/*2/*3/*17, and investigated for susceptibility to antimicrobial agents, received vonoprazan-containing regimens: (1) With amoxicillin and clarithromycin as the first-line treatment; (2) with amoxicillin and metronidazole as the second-line treatment; or (3) with amoxicillin and sitafloxacin as the third-line treatment. Results: The eradication rate was 84.5% (95% confidence interval [CI]: 78.9–89.1%) using first-line, 92.6% (95% CI: 82.1–97.9%) using second-line and 87.5% (95% CI: 73.1–95.8%) using third-line treatment. Infection with clarithromycin-resistant strains was a predictive factor for failed eradication (odds ratio: 5.788, 95% CI: 1.916–17.485, p = 0.002) in multivariate analysis. No significant differences were observed in the eradication rate of regimens among CYP3A4, CYP3A5 and CYP2C19 genotypes. Conclusions: Genotyping for CYP3A4 *1/*22, CYP3A5 *1/*3 and CYP2C19 *1/*2/*3/*17 before vonoprazan-containing eradication treatment may not be useful for predicting clinical outcomes.

scholarly journals Current status of first- and second-line Helicobacter pylori eradication therapy in the metropolitan area: a multicenter study with a large number of patients

2019 ◽  
Vol 12 ◽  
pp. 175628481985851 ◽  
Author(s):  
Hideki Mori ◽  
Hidekazu Suzuki ◽  
Fumio Omata ◽  
Tatsuhiro Masaoka ◽  
Daisuke Asaoka ◽  
...  
Keyword(s):  
Helicobacter Pylori ◽  
Metropolitan Area ◽  
Eradication Rate ◽  
Eradication Therapy ◽  
Second Line ◽  
Independent Factor ◽  
First Line ◽  
Helicobacter Pylori Eradication ◽  
First Line Therapy ◽  
Line Therapy

Background: The environment surrounding Helicobacter pylori eradication treatment is dramatically changing. Recently, vonoprazan, a first-in-class potassium-competitive acid blocker (P-CAB), was introduced onto the market in 2015. The aging of Japan’s demographic structure is becoming pronounced. In this study, we examined the trend of the eradication rate of H. pylori in the metropolitan area and examined factors concerning successful eradication. Methods: We collected data from 20 hospitals in the Tokyo metropolitan area on patients who received first-line eradication therapy with a proton-pump inhibitor (PPI)/P-CAB, amoxicillin, and clarithromycin for 1 week and second-line eradication therapy with a PPI/P-CAB, amoxicillin, and metronidazole for 1 week from 2013 to 2018. The annual eradication rate and associated factors for successful eradication were analyzed. Results: We collected data of 4097 and 3572 patients in the first- and second-line eradication therapies, respectively. The eradication rate decreased from 2013 to 2014 and increased again from 2015 to 2018 with the first-line therapy [the eradication rates in 2013, 2014, 2015, 2016, 2017 and 2018 were 71.8%, 63.7%, 78.5%, 84.6%, 89.7 and 90.1%, respectively, in the per protocol (PP)]. The second-line eradication rates were 90.0%, 82.6%, 88.8%, 87.5%, 91.8% and 90.1% in 2013, 2014, 2015, 2016, 2017 and 2018, respectively, in PP. Vonoprazan was an independent factor for successful eradication in not only first-line, but also second-line eradication. Age over 75 years was an independent factor for eradication failure in both first- and second-line eradication therapies. Conclusion: The eradication rate improved from 2015 to 2018 with the first-line therapy because of the introduction of vonoprazan in the market. The eradication rates with first- and second-line regimens in elderly patients were lower than those in younger patients.

scholarly journals Efficacy of Levofloxacin Based Triple and High-Dose PPI-Amoxicillin Dual Eradication Therapy for Helicobacter pylori after Failures of First- and Second-Line Therapies

2014 ◽  
Vol 2014 ◽  
pp. 1-6 ◽  
Author(s):  
Kenichiro Okimoto ◽  
Makoto Arai ◽  
Keiko Saito ◽  
Shoko Minemura ◽  
Daisuke Maruoka ◽  
...  
Keyword(s):  
Helicobacter Pylori ◽  
Triple Therapy ◽  
Eradication Rate ◽  
Eradication Therapy ◽  
High Dose ◽  
Second Line ◽  
Intention To Treat ◽  
The Third ◽  
Significant Difference ◽  
Third Line

Objectives. The aim of this study was to investigate and compare the eradication rate of Helicobacter pylori as the third-line triple therapy with rabeprazole (RPZ) + amoxicillin (AMPC) + levofloxacin (LVFX) and high-dose RPZ + AMPC. Methods. 51 patients who failed Japanese first-line (proton pump inhibitor (PPI) + AMPC + clarithromycin) and second-line (PPI + AMPC + metronidazole) eradication therapy were randomly assigned at a 1 : 1 ratio to one of the following third-line eradication groups: (1) RAL group: RPZ 10 mg (b.i.d.), AMPC 750 mg (b.i.d.), and LVFX 500 mg (o.d.) for 10 days; (2) RA group: RPZ 10 mg (q.i.d.) and AMPC 500 mg (q.i.d.) for 14 days. Patients who failed to respond to third-line eradication therapy received salvage therapy. Results. The rates of eradication success, based on intention to treat (ITT) analysis, were 45.8% in the RAL group and 40.7% in the RA group. The overall eradication rates were 73.9% in the RAL group and 64.0% in the RA group. There was no significant difference between the two groups. Conclusions. The third-line triple therapy with RPZ, AMPC, and LVFX was as effective as that with high-dose RPZ and AMPC.

scholarly journals Sa1910 Time Trends for Helicobacter pylori Eradication Rate of the First-Line and Second-Line Japanese Regimens and Clarithromycin Resistance

2013 ◽  
Vol 144 (5) ◽  
pp. S-332 ◽  
Author(s):  
Naoko Tsuji ◽  
Naoki Okumura ◽  
Satoko Taniike ◽  
Takehisa Takaba ◽  
Nozomu Matsumoto ◽  
...  
Keyword(s):  
Helicobacter Pylori ◽  
Time Trends ◽  
Eradication Rate ◽  
Second Line ◽  
First Line ◽  
Helicobacter Pylori Eradication ◽  
Clarithromycin Resistance

scholarly journals Disease Management and Resource Use for the Management of Melanoma stage IIIc or IV Positive for BRAF V600 Mutations in Greece

2021 ◽  
Vol 2 (1) ◽  
Author(s):  
Carayanni V ◽  
Gogas H ◽  
Bafaloukos D ◽  
Boukovinas I ◽  
Latsou D ◽  
...  
Keyword(s):  
Resource Use ◽  
Line Treatment ◽  
Second Line ◽  
First Line ◽  
Cost Of Treatment ◽  
Management Scenario ◽  
Third Line ◽  
The Cost ◽  
Third Line Treatment ◽  
First Line Treatment

Objective: Melanoma is one of the most aggressive cancers and is responsible for the majority of skin cancer deaths, with the presence of metastases prognostic for poor survival. At a time when most cancer incidences are falling, the annual incidence of melanoma has risen as rapidly as 4-6% in many European countries, with a substantial economic burden in advanced stages. The objective of this study is the investigation of treatment pathways and healthcare resource use related to advanced BRAF-mutated melanoma in Greece. Methods: This study is based on the information collected by an expert panel comprising of 3 oncologists of major public and private melanoma clinics around Greece. A 3-round survey was undertaken, according to a modified Delphi method. The treatment phases studied were: pre-progression; disease progression and terminal care. Oncology drug costs, medical visits, laboratory tests, imaging examinations, hospitalization and concomitant medications were the resources considered in the context of the Greek National Services Organization (EOPYY). Results: Τhe most common management scenario (80% of cases) in Greece for patients of stage IV BRAF V600 mutated melanoma was: targeted therapies as first line treatment at 95%, followed by immunotherapies at 100% as second line as well as third line treatment at 65% of cases. The weighted annual cost of treatment was 89.215,78 €, (90%CI:62,451.05; 115,980.51) for first line treatment at list price and around 41.584,50 (90%CI:29,109.15; 54,059.85) based on the negotiated price. At second line, the cost of treatment has been estimated between 15,704.272 (90%CI:10,992.990; 20,415.553) and 19,800.92€, (90%CI: 16,489; 30,622) for the two most common management scenarios for immunotherapies. For third line treatment the cost was 37,778.93 (90%CI 26,445.25; 49,112.61€) for the mostly used management scenario (50% ipilimumab). Conclusions: Μetastatic BRAF mutant melanoma requires prolonged and costly treatment with new therapies shown to substantially increase life expectancy. Identifying the appropriate treatment options in order to optimize health outcomes should be an important priority in healthcare system.

scholarly journals Therapeutic Efficacy and Safety of Lenvatinib for Unresectable Hepatocellular Carcinoma Beyond Progression with Sorafenib

2020 ◽  
Author(s):  
Tetsu Tomonari ◽  
Yasushi Sato ◽  
Hironori Tanaka ◽  
Takahiro Tanaka ◽  
Yasuteru Fujino ◽  
...  
Keyword(s):  
Signal Transduction ◽  
Signal Transduction Pathways ◽  
Line Treatment ◽  
Second Line ◽  
Efficacy And Safety ◽  
First Line ◽  
Array Analysis ◽  
Third Line ◽  
Protein Array Analysis ◽  
Third Line Treatment

AbstractBackground & AimsThe efficacy and safety of lenvatinib (LEN) as a second/third-line treatment for unresectable hepatocellular carcinoma (HCC) after sorafenib (SOR) therapy remains unknown. We evaluated the outcomes of second/third-line treatment of LEN, investigated the sensitivity of SOR-resistant HCC cell line (PLC/PRF5-R2) to LEN, and their signal transduction pathway by protein array analysis.MethodsWe retrospectively enrolled 57 unresectable HCC patients. Radiologic responses in 53 patients were evaluated by modified Response Evaluation Criteria in Solid Tumors. Active signal transduction pathways in cells were identified by protein array analysis, including 1205 proteins.ResultsPatients comprised 34 tyrosine kinase inhibitor (TKI)-naive (first-line), nine SOR-intolerant (second-line), and ten resistant to regorafenib (third-line). Objective response rates (ORRs) were 61.8% (21/34) in TKI-naive, 33.3% (3/9) in second-line, and 20.0% (2/10) in third-line groups. The overall survival (OS) and the progression free survival (PFS) in the first-line was significantly longer than those in third-line group (p<0.05). Patients with better liver functional reserve (Child score, ALBI grade) exhibited higher ORR and longer OS. LEN was well-tolerated as second/third-line treatment. The IC50 value of LEN against PLC/PRF5-R2 cells (30 μM) was significantly higher than that against PLC/PRF5 cells (6.4 μM). LEN inhibited significantly more signal transduction pathways related to FRS2, a crucial FGFR downstream molecule, in PLC/PRF5 than PLC/PRF5-R2 cells.ConclusionsLEN was active and safe as a second/third-line treatment for unresectable HCC. LEN seems to be more effective for HCC patients with better hepatic reserve function or before TKI-resistance is acquired because of partial cross-resistance to SOR.

Efficacy and safety of taxane-monotherapy in advanced gastric cancer refractory to triplet chemotherapy with docetaxel, cisplatin, and S-1: A multicenter retrospective study.

2017 ◽  
Vol 35 (4_suppl) ◽  
pp. 154-154
Author(s):  
Sadayuki Kawai ◽  
Sakura Iizumi ◽  
Atsuo Takashima ◽  
Yukiya Narita ◽  
Masahiro Tajika ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Advanced Gastric Cancer ◽  
Line Treatment ◽  
Second Line ◽  
Efficacy And Safety ◽  
First Line ◽  
The Third ◽  
Third Line ◽  
Ecog Ps ◽  
Third Line Treatment

154 Background: While taxane-monotherapy following fluoropyrimidine plus platinum is recognized as the standard treatment strategy for advanced gastric cancer, triplet chemotherapy with docetaxel, cisplatin and S-1 (DCS) is another option for first-line therapy in Japan. However, efficacy of taxane after DCS therapy has not been sufficiently evaluated. Methods: We retrospectively evaluated the efficacy and safety of taxane-monotherapy after DCS between January 2010 and April 2015 for advanced gastric cancer. The taxane-monotherapy included weekly paclitaxel (PTX) (80 mg/m2, day 1, 8 and 15 of a 28-day cycle) and triweekly nab-PTX (260 mg/m2, day 1). Other selection criteria were: ECOG PS < 2; adequate organ function; no severe ascites; HER2-negative. Results: Thirty of 92 patients who had been treated with DCS received taxane-monotherapy. Fifteen and 15 patients received taxane-monotherapy as the second and third-line treatment, respectively. Patients characteristics of each group (2nd/3rd) were; median age: 64/62 (range 27-75/42-75); ECOG PS ≤ 1: 14/13; number of metastatic sites ≥ 2: 9/12; median taxane-free interval from first-line treatment: 1.6/3.4 (range 0.9-2.3/2.2-8.3) months; median total dose of prior DTX: 349/208 (range 39-844/141-685) mg/m2. Number of patients who received PTX/nab-PTX were 10/5 and 13/2 in the second and third line treatment. Median relative dose intensity of taxane was 96.4% (range 57.6-172.9%) in the second-line, 98.5% (44.0-166.8%) in the third-line group. Response rate and disease control rate were 0% and 37.5% in the second-line, and 0% and 38.5% in the third-line group. Median progression free survival and overall survival were 3.4 and 5.8 months in the second-line group, and 2.0 and 4.5 months in the third-line. Grade 3 or 4 neutropenia, anemia, and anorexia, occurred in 33%, 13% and 13% in the second-line group, and 6.7%, 13% and 6.7% in the third–line group, associated with no treatment related death. Conclusions: It is suggested that taxane-monotherapy has acceptable toxicities but insufficient efficacy in advanced gastric cancer patients after DCS therapy.

Safety and Efficacy of Bortezomib and Dexamethasone (BD) in Multiple Myeloma as First-Line, Second-Line or Third-Line Treatment.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 4817-4817
Author(s):  
Juan Li ◽  
Beihui Huang ◽  
Ying Zhao ◽  
Dong Zheng ◽  
Shaokai Luo
Keyword(s):  
Multiple Myeloma ◽  
Peripheral Neuropathy ◽  
Median Time ◽  
Median Number ◽  
Line Treatment ◽  
Second Line ◽  
First Line ◽  
Line Therapy ◽  
Third Line ◽  
Third Line Treatment

Abstract Purpose: To compare efficacy and safety of BDbortezomib and dexamethasone in multiple myeloma as first-line, second-line or third-line treatment. Patients and methods: 18 patients(pts) treated with BD (bortezomig 1.3mg/m2 on d 1,4,8,11 and dexamethasone 20mg on d 1–4 in a 21-day cycle). Responses were evaluated by the criteria of EBMT but a nCR was included. Adverse events were graded by the WHO criteria. Results: The median age was 52.5 years, and 13 (72.2%) were male. Ig subtypes were IgG, (8 pts, 44.4%), IgA (4 pts, 22.2%), light chain (2 pts, 11.1%), and IgD (1 pts, 5.9%). Durine/Salmon staging: IIA 5.9% (1/18), IIB 5.9% (1/18), IIIA 72.2% (13/18), IIIB16.6% (3/18). BD was administered in first-line (4 pts, 22.2%), second-line (7 pts 38.9%) and third-line (7 pts, 38.9%). The median number of BD cycles was 2.5 (range, 1–6 cycles). 17 pts could be evaluated, overall response was 88.3%, including CR in 2 pts (11.7%), nCR in 5 pts (29.4%), PR in 7 pts (41.2%), MR in 1 pts(5.9%), NC in 1 pts(5.9%), PD in 1 pts(5.9%). Pts in the first-line group received a response of 100%(4/4), including nCR in 1 pts (25.0%), PR in 2 pts (50.0%), MR in 1 pts(25.0%). The second-line group received a response of 100%(7/7), including CR in 1 pts(14.3%), nCR in 3 pts (42.9%), PR in 3 pts (42.9%). Those received BD as third-line or more got a response of 66.7% (4/6), including CR in 1 pts(16.7%), nCR in 1 pts (16.7%), PR in 2 pts (33.3%). Aderse events included diarrhea 44.4% (8/18; grade IV: 2/18), thrombocytopenia 44.4% (8/18; grade III–IV: 7/18), fatigue 44.4% (8/18; grade IV: 1/18), peripheral neuropathy 33.3% (6/18, grade II:1/18), pyrexia 22.2%, infection 16.7% (3/18), headache 11.1%(2/18), parageusis 11.1%(2/18), hypotension 5.9%(1/18), hypoglycemia 5.9%(1/18) while combining with glipizide. The median time to minimum counts of platets was 14 days. The median time to most serious peripheral neuropathy appeared after treatment of 3 cycles. In 1 pts the therapy was disrupted by toxicity. Conclusion: BD demonstrated better response as first-line or second-line therapy than as third or more line therapy. Toxicities were torelated and manegable. There were no treatment related deaths.

Chemothery (pacitaxol or irinotecan), plus apatinib and sintilimab as second-/third-line treatment for advanced gastric cancer.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e16080-e16080
Author(s):  
Ting Deng ◽  
Le Zhang ◽  
Jingjing Duan ◽  
Hongli Li ◽  
Shaohua Ge ◽  
...  
Keyword(s):  
Adverse Events ◽  
Objective Response ◽  
Line Treatment ◽  
Second Line ◽  
First Line ◽  
Elevated Alkaline Phosphatase ◽  
Second Line Chemotherapy ◽  
Third Line ◽  
Line Chemotherapy ◽  
Third Line Treatment

e16080 Background: Patients with advanced gastric or gastro-esophageal junction cancer have poor prognosis after progression on first-line chemotherapy. We investigated to combine second-line chemotherpy with third-line drugs, apatinib and anti-PD-1 antibody in these patients. Methods: This study is a single center, exploratory study in China. Eligible patients are adults with histologically confirmed advanced gastric or GEJ adenocancinoma, who were failure of first-line or second-line chemotherapy. Subjects receive chemotherapy, pacitaxol or iritecan (investigator choice), apatinib 250mg po qd, sintilimab 200mg ivd q3w. Response was assessed every 6 weeks. (RECIST version1.1) Primary endpoint was progression free survival (PFS). Results: Between May 30, 2019 and November 5, 2020, a total of 26 patients were enrolled in this study, and 4 (15.4%) patients were failure of second-line chemotherapy. There were 21 males and 5 females, and the median age was 61. The total number of treatment cycles was 140 and the median number was 5.5. Among 24 patients who were evaluated, partial response (PR) was obtained in 12 cases, stable disease (SD) in 8 cases and progressive disease (PD) in 4 cases. Objective response rate was 50.0%，and disease control rate was 83.3%. The median PFS was 7.06 months (95% CI 5.52-8.60), and the median overal survival has not yet been reached. The most common adverse events (AE) were leukopenia (61.5%), anemia (57.7%), neutropenia (53.8%), proteinuria (42.3%), alopecia (42.3%), hypothyroidism (38.5%), elevated alanine aminotransferase (34.6%), elevated aspartate aminotransferase (34.6%) and elevated alkaline phosphatase (34.6%), but most of them were grade 1 or 2, and the most common grade 3 or 4 treatment-related adverse events was neutropenia (11.5%). Conclusions: Chemotherapy, plus apatinib and sintilimab demonstrated promising activity and manageable safety profile as second- even third-line treatment in advanced gastric or GEJ cancer. Demographics and baseline characteristics.[Table: see text]

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