Objective:Paclitaxel(P)is a standard second-line chemotherapy in the treatment of advanced gastric cancer.This study compared the clinical outcome of a paclitaxel plus raltitrexed(RP)regimen as second-line treatment i...Objective:Paclitaxel(P)is a standard second-line chemotherapy in the treatment of advanced gastric cancer.This study compared the clinical outcome of a paclitaxel plus raltitrexed(RP)regimen as second-line treatment in metastatic gastric cancer(MGC)patients.Methods:An open,randomized,multi-center phase Ⅱ clinical trial was conducted involving 148 patients who were randomly assigned and treated with RP[raltitrexed(3 mg/m^(2)on day 1)and paclitaxel(135 mg/m^(2)on day 1 every 3 weeks)]or P[paclitaxel(135 mg/m^(2)on day 1 every 3 weeks)]as 2nd-line chemotherapy.The primary endpoint was progression-free survival(PFS).The secondary endpoints were the overall response rate(ORR),overall survival(OS),and safety.Results:PFS had a tendency to be prolonged with RP compared to P(2.7 months vs.1.7 months;P=0.148).OS was also prolonged with RP compared to P(10.2 months vs.6.1 months;P=0.140).The ORR was equal in the RP and P groups(6.8%and 4.0%;P=0.72).The disease control rate(DCR)in the RP and P groups was 56.2%and 36.0%,respectively.Grade 3-4 treatment-related adverse events occurred in 36.2%(RP)and 28.2%(P)of patients.Frequent grade 3-4 toxicities for RP and P were neutropenia(11.0%and 4.0%),anemia(1.4%and 4.0%),and thrombocytopenia(1.4%and 5.3%),and all grades of peripheral neurotoxicity(12.3%vs.17.3%).All grades of hepatic toxicity were demonstrated for the RP and P groups based on elevated aminotransferase levels(27.4%and 14.1%).Subgroup analysis shows if MGC was combined with ascites or peritoneal involvement,the OS of the RP regimen was longer(P=0.05).Conclusions:Second-line palliative chemotherapy with RP was shown to prolong the PFS and OS,especially among patients with ascites or peritoneal involvement,which warrants confirmation using larger sample studies.展开更多
Gastric cancer remains one among the leading causes of cancer-related deaths, regardless of its decreasing incidence and newly available treatment options. Most patients present at an advanced stage and are treated wi...Gastric cancer remains one among the leading causes of cancer-related deaths, regardless of its decreasing incidence and newly available treatment options. Most patients present at an advanced stage and are treated with upfront systemic chemotherapy. Those patients receiving first-line therapy may initially respond to treatment, but many of them relapse over time. In such condition, second-line treatment for disease progression remains the only available option. Although there exists no standard approach in the second-line setting, several phase Ⅲ trials have shown modest survival benefit in patients receiving irinotecan, taxane and ramucirumab over the best supportive care or active agents. This review analyzes the currently available treatment regimens and future directions of research in the second-line setting for metastatic gastric cancer with the best available evidence. Additionally, the prognostic factors that influence patient survival in those receiving second-line therapy are discussed.展开更多
AIM: To compare the efficacy of 14- and 7-d bismuthbased quadruple therapies as second-line eradication treatment for Helicobacter pylori(H.pylori) infection.METHODS: Between 2004 and 2014,the medical records of 790 p...AIM: To compare the efficacy of 14- and 7-d bismuthbased quadruple therapies as second-line eradication treatment for Helicobacter pylori(H.pylori) infection.METHODS: Between 2004 and 2014,the medical records of 790 patients who had experienced failure of first-line proton pump inhibitor(PPI)-based eradication therapy and were then treated with bismuth-based quadruple therapy were retrospectively reviewed.Those who received bismuth-based quadruple therapy [PPI,bismuth,metronidazole,and tetracycline(PBMT)] for either 7 d or 14 d were assigned to a PBMT-7 group(n = 543) or a PBMT-14 group(n = 247),respectively.The eradication rates for both groups were determined by intention-to-treat(ITT) and per-protocol(PP) analyses.ITT analysis compared the treatment groups as originally allocated while the PP analysis including only those patients who had completed the treatment as originally allocated.Successful eradication therapy for H.pylori infection was defined as a negative 13C-urea breath test 4 wk after the end of eradication treatment.RESULTS: The overall ITT eradication rate was 69.1%(546/790).Final ITT eradication rates were 67.4%(366/543; 95%CI: 63.1%-71.7%) in the PBMT-7 group and 72.8%(180/247; 95%CI: 67.4%-78.2%) in the PBMT-14 group(P = 0.028).The overall PP eradication rate was 80.0%(546/682),and the final PP eradication rates were 78.2%(366/468; 95%CI: 72.1%-84.0%) in the PBMT-7 group and 84.1%(180/214; 95%CI: 76.8%-90.8%) in the PBMT-14 group(P = 0.009).The H.pylori eradication rates in the PBMT-14 group weresignificantly higher than in the PBMT-7 group according to both ITT(P = 0.028) and PP analysis(P = 0.009).Compliance was similar in both groups(PBMT-7 group: 97.9%; PBMT-14 group: 96.4%).Adverse event rates were 10.7%(51/478) and 17.1%(38/222) in the PBMT-7 and PBMT-14 groups,respectively(P = 0.487).CONCLUSION: The 14-d bismuth-based quadruple therapy is a significantly more effective second-line eradication treatment for H.pylori infection than the 7-d alternative.展开更多
BACKGROUND The standard management of autoimmune hepatitis(AIH)is based on corticosteroids,alone or in combination with azathioprine.Second-line treatments are needed for patients who have refractory disease.However,h...BACKGROUND The standard management of autoimmune hepatitis(AIH)is based on corticosteroids,alone or in combination with azathioprine.Second-line treatments are needed for patients who have refractory disease.However,high-quality data on the alternative management of AIH are scarce.AIM To evaluate the efficacy and safety of tacrolimus and mycophenolate mofetil(MMF)and the quality of evidence by using the Grading of Recommendations Assessment,Development and Evaluation approach(GRADE).METHODS A systematic review and meta-analysis of the available data were performed.We calculated pooled event rates for three outcome measures:Biochemical remission,adverse events,and mortality,with their corresponding 95%confidence intervals(CI).RESULTS The pooled biochemical remission rate was 68.9%(95%CI:60.4-76.2)for tacrolimus,and 59.6%(95%CI:54.8-64.2)for MMF,and rates of adverse events were 25.5%(95%CI:12.4-45.3)for tacrolimus and 24.1%(95%CI:15.4-35.7)for MMF.The pooled mortality rate was estimated at 11.5%(95%CI:7.1-18.1)for tacrolimus and 9.01%(95%CI:6.2-12.8)for MMF.Pooled biochemical remission rates for tacrolimus and MMF in patients with intolerance to standard therapy were 56.6%(CI:43.4-56.6)vs 73.5%(CI:58.1-84.7),and among non-responders were 59.1%(CI:48.7-68.8)vs 40.8%(CI:32.3-50.0),respectively.Moreover,the overall quality assessments using GRADE proved to be very low for all our outcomes in both treatment groups.CONCLUSION Tacrolimus and MMF are in practice considered effective for patients with AIH who are non-responders or intolerant to first-line treatment,but we found no high-quality evidence to support this statement.展开更多
Background: Capecitabine and irinotecan combination therapy(XELIRI) has been examined at various dose levels to treat metastatic colorectal cancer(m CRC). Recently, in the Association of Medical Oncology of the German...Background: Capecitabine and irinotecan combination therapy(XELIRI) has been examined at various dose levels to treat metastatic colorectal cancer(m CRC). Recently, in the Association of Medical Oncology of the German Cancer Society(AIO) 0604 trial, tri?weekly XELIRI plus bevacizumab, with reduced doses of irinotecan(200 mg/m^2 on day 1) and capecitabine(1600 mg/m^2 on days 1–14), repeated every 3 weeks, has shown favorable tolerability and eicacy which were comparable to those of capecitabine and oxaliplatin(XELOX) plus bevacizumab. The doses of capecit?abine and irinotecan in the AIO trial are considered optimal. In a phase I/II study, XELIRI plus bevacizumab(BIX) as second?line chemotherapy was well tolerated and had promising eicacy in Japanese patients.Methods: The Asian XELIRI Projec T(AXEPT) is an East Asian collaborative, open?labelled, randomized, phase Ⅲ clinical trial which was designed to demonstrate the non?inferiority of XELIRI with or without bevacizumab versus standard FOLFIRI(5?fluorouracil, leucovorin, and irinotecan combination) with or without bevacizumab as second?line chemo?therapy for patients with m CRC. Patients with 20 years of age or older, histologically conirmed m CRC, Eastern Coop?erative Oncology Group performance status 0–2, adequate organ function, and disease progression or intolerance of the irst?line regimen will be eligible. Patients will be randomized(1:1) to receive standard FOLFIRI with or with?out bevacizumab(5 mg/kg on day 1), repeated every 2 weeks(FOLIRI arm) or XELIRI with or without bevacizumab(7.5 mg/kg on day 1), repeated every 3 weeks(XELIRI arm). A total of 464 events were estimated as necessary to show non?inferiority with a power of 80% at a one?sided α of 0.025, requiring a target sample size of 600 patients. The 95% conidence interval(CI) upper limit of the hazard ratio was pre?speciied as less than 1.3.Conclusion: The Asian XELIRI Projec T is a multinational phase III trial being conducted to provide evidence for XELIRI with or without bevacizumab as a second?line treatment option of mCRC.展开更多
Dasatinib is a second-generation tyrosine kinase inhibitor (TKI)and it could be used as a second-line treatment for patients with chronic myeloid leukemia (CML).Yinishu,a generic dasatinib made in China,was approved b...Dasatinib is a second-generation tyrosine kinase inhibitor (TKI)and it could be used as a second-line treatment for patients with chronic myeloid leukemia (CML).Yinishu,a generic dasatinib made in China,was approved by the China Food and Drug Administration in 2013 and it costs much less than the patented dasatinib SPRYCEL.The present study aimed to examine the efficacy and safety of Yinishu as a second-line treatment for CML by comparing the baseline clinical characteristics,rates of adverse events and efficacy between Yinishu and SPRYCEL groups. The results showed that there were no significant differences in the rates of optimal response between Yinishu and SPRYCEL for patients who started second-line treatment because of treatment failure.For patients who started second-line treatment because of intolerance of first-line treatment, their levels of BCR-ABL1/ABL1 on the international scale (BCR-ABL^IS)was maintained very low throughout the course of Yinishu treatment.Drug-related adverse events occurred with the same frequency in these two groups.It was confirmed that Yinishu was effective and safe as a second- line treatment for CML patients.Yinishu may be more suitable for patients who are economically unable to pay for the patented dasatinib SPRYCEL.展开更多
AIM: To evaluate the efficacy of the 14-d moxifloxacinbased triple therapy for the second-line eradication of Helicobacter pylori(H. pylori) infection.METHODS: Between 2011 and 2013, we conducted a retrospective revie...AIM: To evaluate the efficacy of the 14-d moxifloxacinbased triple therapy for the second-line eradication of Helicobacter pylori(H. pylori) infection.METHODS: Between 2011 and 2013, we conducted a retrospective review of the medical records of 160 patients who had experienced failure of their first-line proton pump inhibitor-based eradication therapy and subsequently received the moxifloxacin-based triple therapy as a second-line eradication treatment regimen. The patients who were treated with the moxifloxacinbased triple therapy(oral 20 mg rabeprazole b.i.d., 1000 mg amoxicillin b.i.d., and 400 mg moxifloxacin q.d.) for 7 d were assigned to the RAM-7 group(n = 79) while those who took them for 14 days were assigned to RAM-14 group(n = 81). The eradication rates for both groups were determined by intentionto-treat(ITT) and per-protocol(PP) analyses. ITT analysis compared the treatment groups as originally allocated while the PP analysis including only those patients who had completed the treatment as originally allocated. Successful eradication therapy for H. pylori infection was defined as the documentation of a negative 13C-urea breath test 4 wk after the end of the eradication treatment.RESULTS: The overall ITT eradication rate was 76.2%(122/160). The final ITT eradication rates were 70.8%(56/79; 95%CI: 63.3%-77.1%) in the RAM-7 group and 81.4%(66/81; 95%CI: 74.6%-88.3%) in the RAM-14 group(P = 0.034). The overall PP eradication rate was 84.1%(122/145), and the final PP eradication rates were 77.7%(56/72; 95%CI: 70.2%-85.3%) in the RAM-7 group and 90.4%(66/73; 95%CI: 82.8%-98.1%) in the RAM-14 group(P = 0.017). The H. pylori-eradication rates in the RAM-14 group were significantly higher compared with that of the RAM-7 group according to both the ITT(P = 0.034) and the PP analyses(P = 0.017). Both groups exhibited good treatment compliance(RAM-7/RAM-14 group: 100%/100%). The adverse event rates were19.4%(14/72)and 20.5%(15/73)in the RAM-7 and RAM-14 groups,respectively(P=0.441).Adverse events occurred in 14 of the 72 patients(19.4)in the RAM-7 group and in 15 of the 73 patients(20.5)in the RAM-14 group.No statistically significant differences(P=0.441)were observed.CONCLUSION:The 14-d moxifloxacin-based triple therapy is a significantly more effective secondline eradication treatment as compared to the 7-d alternative for H.pylori infection in South Korea.展开更多
Over the past ten years,sorafenib,a multikinase inhibitor,has been the standard of care for patients with unresectable hepatocellular carcinoma(HCC)and wellpreserved liver function.Recently,lenvatinib,a different mult...Over the past ten years,sorafenib,a multikinase inhibitor,has been the standard of care for patients with unresectable hepatocellular carcinoma(HCC)and wellpreserved liver function.Recently,lenvatinib,a different multikinase inhibitor,was shown to be non-inferior to sorafenib,in terms of survival,while all other agents previously tested failed to prove non-inferiority(or superiority)when compared to sorafenib.Similarly,in the second-line setting,most investigational drugs failed to provide better survival outcomes than placebo.However,in the last 2 years three positive phase III trials have been published in this setting.The RESORCE trial,a phase III study evaluating regorafenib in HCC patients who experienced disease progression after first-line treatment with sorafenib,showed better outcomes with regorafenib compared to placebo.More recently,the phase III CELESTIAL trial demonstrated the superiority of cabozantinib,a multikinase inhibitor targeting vascular endothelial growth factor receptor,MET,and AXL,vs placebo in the second-and third-line setting in patients progressing on or intolerant to sorafenib.The survival benefits of a sustained anti-angiogenic inhibition were demonstrated also with ramucirumab in the phase III REACH-2 trial in patients previously treated with sorafenib and who had high baseline alpha-fetoprotein levels.Overall,the adverse events reported in these trials were in line with the known safety profiles of the tested agents.After nearly a decade of a certain degree of stagnation,we are now witnessing a period of novel therapeutic advances with multikinase inhibitors and monoclonal antibodies that will likely change the treatment scenario of HCC.展开更多
BACKGROUND There is no standard therapy for second-line treatment of gemcitabine-refractory pancreatic cancer patients with poor performance status.A combination of chemotherapy drugs 5-fluorouracil(5-FU),leucovorin,i...BACKGROUND There is no standard therapy for second-line treatment of gemcitabine-refractory pancreatic cancer patients with poor performance status.A combination of chemotherapy drugs 5-fluorouracil(5-FU),leucovorin,irinotecan,and oxaliplatin(FOLFIRINOX)or 5-fluorouracil/leucovorin plus nanoliposomal irinotecan can be considered as second-line treatment for such patients;however,due to toxicity,none of the regimens are recommended for patients with poor performance.Capecitabine or S-1 has relatively low toxicity and can be considered a treatment option for gemcitabine-refractory pancreatic cancer.AIM To investigate the efficacy and toxicity of oral chemotherapy as second-line treatment in patients with pancreatic cancer.METHODS Patients who had progressive disease after first-line gemcitabine-based chemotherapy were retrospectively analyzed between January 2011 and December 2018.They were treated with capecitabine or S-1 as the second-line treatment.Capecitabine was administered as a 2500 mg/m2 divided dose on days 1-14,followed by a 1-wk rest.S-1 was taken orally based on the patient’s body surface area for 28 d,followed by 2-wk of rest.Progression-free survival and overall survival were used to compare efficacy of capecitabine and S-1.RESULTS Of the 81 patients,41 were treated with capecitabine and 40 with S-1.The median time to treatment failure in both groups was 1.5 mo(P=0.425).The objective response rate was similar in the two groups:9.8%with capecitabine and 2.5%with S-1(P=0.359).Median progression-free survival was longer in the S-1 group than in the capecitabine group(S-12.7 mo,capecitabine 2.0 mo,P=0.003).There was no significant difference in the median overall survival between the capecitabine and S-1 groups(4.3 mo vs 5.0 mo,P=0.092).Grade 3 or 4 hand-foot syndrome was significantly more common in the capecitabine group than in the S-1 group(14.6%vs 0%,P=0.026).CONCLUSION Capecitabine or S-1 can be used as a second-line treatment for patients with advanced pancreatic cancer with poor performance status after progression to a gemcitabine-based regimen.展开更多
Objective:Several studies have demonstrated different benefits for patients whose disease progressed despite previous trastuzumab treatment.Due to limited real-world data,we evaluate the effectiveness of anti-human ep...Objective:Several studies have demonstrated different benefits for patients whose disease progressed despite previous trastuzumab treatment.Due to limited real-world data,we evaluate the effectiveness of anti-human epidermal growth factor receptor 2(HER2)therapy(lapatinib or trastuzumab)plus chemotherapy or chemotherapy alone in patients who were previously treated with trastuzumab-containing regimens and investigate factors associated with effectiveness.And we further show the effectiveness of the two anti-HER2 therapy groups.Methods:A total of 342 HER2-positive metastatic breast cancer(MBC)patients whose disease progressed during prior anti-HER2(trastuzumab)and standard chemotherapy therapy from Department of Breast Oncology,the Fifth Medical Center of Chinese PLA General Hospital,from August 2010 to December 2016 were included.Seventy-eight patients received standard chemotherapy only,148 patients continued to receive trastuzumab and switched to other chemotherapy drugs,and 116 patients received tyrosine-kinase inhibitors(TKIs;lapatinib)and chemotherapy.The main outcome measures were progression-free survival(PFS),overall response rate(ORR),and clinical benefit rate(CBR).Subgroup analyses were conducted to identify patient characteristics associated with the greatest clinical benefit.Results:After a median follow-up of 26.2(range,2.0-56.0)months,PFS significantly improved with anti-HER2 therapy compared with chemotherapy alone:median 6.0 months with lapatinib[95%confidence interval(95%CI),4.53-7.47],4.5 months with trastuzumab(95%CI,3.99-5.01)vs.3.0 months with chemotherapy alone(95%CI,2.42-3.58);stratified hazard ratio(HR)=0.70,95%CI,0.60-0.81;P<0.0001.The ORR values were 33.6%,25.0%and 12.8%,respectively,the CBR values were 60.3%,48.6%and 26.9%,respectively.The effectiveness of lapatinib group and trastuzumab group were further analyzed.In multivariate analysis,lapatinib group was associated with a longer PFS,after controlling other potential confounders(HR=0.68,95%CI,0.52-0.90;P=0.006).Conclusions:The combination of TKIs and chemotherapy was effective in this cohort previously treated with trastuzumab treatment.Therefore,TKIs combined with chemotherapy is an option for Chinese HER2-positive MBC patients previously treated with trastuzumab treatment.展开更多
Aims and Background: Irinotecan is a standard option for relapsed/refractory advanced colo- rectal cancer. Combination with raltitrexed and irinotecan at lower than MTD doses should preserve disease stabilisation whil...Aims and Background: Irinotecan is a standard option for relapsed/refractory advanced colo- rectal cancer. Combination with raltitrexed and irinotecan at lower than MTD doses should preserve disease stabilisation while decreasing toxicity. Patients and Methods: From January 2004 to April 2009, we analyzed, retrospectively, our data on irinotecan + raltitrexed, fixed doses, as a second-line chemotherapy in elderly pa- tients (>70 years) with advanced colorectal can- cer after failure of oxaliplatin based chemothera- py twenty-three patients were evaluated. Iri- notecan 350 mg + raltitrexed 2.6 mg were given every 3 weeks. Tumo r measurements were ob- tained after every third course of therapy. Toxic- ity was assessed weekly using the National Cancer Institute Common Toxicity Criteria, ver- sion 2. Results: The median number of treatment courses received per patient was 4 (range, 1 - 8). All pa-tients were assessable for toxicity and 21 for response. The most frequently observed severetoxicities were diarrhea (grade 2, 13%) No cases of significant neutropenia occurred. Ob- jective partial responses were observed in 3 pa- tients (13%). An additional 10 patients (43%) had stable disease as their best response. To date, 12 patients have progressed with a median time- to-progression of 4.3 months and a median sur- vival of 8.3 months. Conclusions: A three weekly irinotecan + raltitrexed administration can indu- ce tumor control in elderly patients with advanc- ed colorectalcancer that has progressed during or shortly after oxaliplatin-based chemotherapy. The diarrhea by irinotecan, seems mitigated by coad-ministration of a smaller dose of展开更多
Hepatocellular carcinoma(HCC)is the most frequently diagnosed primary tumor of the liver and is usually detected as advanced disease.It is an aggressive disease that often progresses rapidly when it fails to respond t...Hepatocellular carcinoma(HCC)is the most frequently diagnosed primary tumor of the liver and is usually detected as advanced disease.It is an aggressive disease that often progresses rapidly when it fails to respond to treatment.As such,patients have limited opportunities to try different subsequent-line treatment regimens.In the last 5 years,the number of agents and/or regimens available for the treatment of advanced HCC has significantly increased,which has made treatment choices for this patient population increasingly complex.In the secondline setting,several phase III trials of regorafenib(RESORCE),ramucirumab(REACH/REACH-2),and cabozantinib(CELESTIAL)have demonstrated clinically meaningful survival benefits in patients with the disease.However,the median overall survival of patients with advanced HCC remains unchanged at approximately 12 mo from the start of systemic second-line therapy,with a limited duration of response.Evidence from the REACH/REACH-2 trials demonstrated for the first time that baseline alpha-fetoprotein(AFP)levels can be used as an identification factor to select those who are likely to benefit the most from ramucirumab treatment.Ramucirumab is both well tolerated and efficacious and has a clinically acceptable safety profile.Therefore,it should be considered an option for patients with AFP levels≥400 ng/mL.展开更多
Aim: To investigate the efficacy and tolerability of second-line metronidazole triple therapy with vonoprazan (VPZ) for Helicobacter pylori (H. pylori). Methods: We retrospectively reviewed medical records of patients...Aim: To investigate the efficacy and tolerability of second-line metronidazole triple therapy with vonoprazan (VPZ) for Helicobacter pylori (H. pylori). Methods: We retrospectively reviewed medical records of patients who experienced clarithromycin triple therapy failure and were treated with second-line (20 mg VPZ (n = 274)/30 mg lansoprazole (n = 323) or 10 mg rabeprazole (n = 141) twice daily, 750 mg amoxicillin twice daily, 250 mg metronidazole twice daily for 7 days) eradication therapies. Successful eradication rates were compared between two groups: those receiving VPZ and those receiving a proton pump inhibitor (PPI). Adverse events were also investigated. Results: Successful second-line eradication rates according to ITT analysis and PP analysis, respectively, were 79.9% and 92.4% for VPZ therapy and 83.6% and 93.3% for PPI therapy. There were no significant differences between treatment groups. The eradication rates in those who had received first-line VPZ therapy previously according to ITT and PP analysis were 75.2% and 88.1%, respectively;in contrast, values were 82.5% and 95.4%, respectively, for those who had received first-line PPI therapy previously. In second-line therapy, the overall adverse event rate for VPZ therapy was the same as for PPI therapy. Conclusions: The efficacy and tolerability of metronidazole-containing second-line triple therapy with VPZ or a PPI were equivalent.展开更多
Despite extensive clinical research in non-small cell lung cancer (NSCLC), overall survival is still poor. Racotumomab-alum is an anti-idiotypic cancer vaccine that targets NeuGcGM3 tumor associated ganglioside. The a...Despite extensive clinical research in non-small cell lung cancer (NSCLC), overall survival is still poor. Racotumomab-alum is an anti-idiotypic cancer vaccine that targets NeuGcGM3 tumor associated ganglioside. The aim of this study was to evaluate safety and efficacy of racotumomab-alum in advanced NSCLC patients with progressive disease. This expanded access program included 86 histologically confirmed NSCLC patients, 18 years or older age, with advanced disease and without therapeutic option, with ECOG performance status ≤3, adequate organ functions and signed informed consent. The primary endpoint was overall survival and toxicity was measure assessed treatment-related toxicity according CTCAEv3. The study was approved by ethical review boards of participant institutions. Racotumomab-alum treatment consisted in 5 biweekly intradermal doses (1 mg/mL) during the induction phase of treatment (2 months). The maintenance phase consisted in monthly re-immunizations until unacceptable toxicity or PS worsening. The median overall survival time of all patients treated with racotumomab-alum was 8.96 months. The survival rates at 12 and 24 months were 42.8% and 28.0%, respectively. Patients that completed the induction phase of treatment (five doses or more) reached a median OS of 12.1 months. The most common adverse events were injection site reaction, bone pain, cough and asthenia. Racotumomab-alum cancer vaccine could be considered an effective and safe treatment option as second-line therapy for advanced NSCLC. Further clinical studies should be conducted to confirm this result.展开更多
Background: Methotrexate, vinblastine, doxorubicin, and cisplatin regimen, and gemcitabine and cisplatin regimen are widely used for advanced or metastatic urothelial carcinomas (UCs). However, a standard treatment fo...Background: Methotrexate, vinblastine, doxorubicin, and cisplatin regimen, and gemcitabine and cisplatin regimen are widely used for advanced or metastatic urothelial carcinomas (UCs). However, a standard treatment for patients who fail these firstline chemotherapies is unavailable. We examined the efficacy and safety of secondline paclitaxel, gemcitabine, and cisplatin (PCG) chemotherapy in Japanese patients. Methods: Between 2004 and 2010, 25 patients with metastatic UCs who failed to respond to platinumbased regimens were treated with PCG. They received intravenous paclitaxel (60 mg/m2) and gemcitabine (1000 mg/m2) on days 1 and 8, and cisplatin (70 mg/m2) on day 2 of every 21 day course. We retrospectively collected patients’ clinical and pathological data and evaluated adverse effects and survivals. Results: Patients underwent 95 PCG cycles in all (average, 3.8 cycles per patient). One patient (4%) achieved complete response, 5 (20%) showed partial response, 8 (42%) had disease stabilization, and 5 (26%) had disease progression. Median overall survival was 8.5 months. Neutropenia and thrombocytopenia of grade ≥ 3 were observed in 68% and 56% of patients, respectively. No treatment related death occurred. Multivariate analysis revealed that hemoglobin levels 1.73 m2) were significant risk factors for overall survival. Conclusion: PCG chemotherapy in the secondline setting potentially contributed to good prognosis in selected patients with relatively significant but tolerable toxicity.展开更多
Worldwide prevalence of Helicobacter pylori(H.pylori) infection is approximately 50%,with the highest being in developing countries.We compared cure rates and tolerability(SE) of second-line anti-H.pylori levofloxacin...Worldwide prevalence of Helicobacter pylori(H.pylori) infection is approximately 50%,with the highest being in developing countries.We compared cure rates and tolerability(SE) of second-line anti-H.pylori levofloxacin/amoxicillin(LA)-based triple regimens vs standard quadruple therapy(QT).An English language literature search was performed up to October 2010.A meta-analysis was performed including randomized clinical trials comparing 7-or 10-d LA with 7-d QT.In total,10 articles and four abstracts were identified.Overall eradication rate in LA was 76.5%(95% CI:64.4%-97.6%).When only 7-d regimens were included,cure rate was 70.6%(95% CI:40.2%-99.1%),whereas for 10-d combinations,cure rate was significantly higher(88.7%;95% CI:56.1%-109.9%;P < 0.05).Main eradication rate for QT was 67.4%(95% CI:49.7%-67.9%).The 7-d LA and QT showed comparable efficacy [odds ratio(OR):1.09;95% CI:0.63-1.87],whereas the 10-d LA regimen was significantly more effective than QT(OR:5.05;95% CI:2.74-9.31;P < 0.001;I 2 = 75%).No differences were reported in QT eradication rates among Asian and European studies,whereas LA regimens were more effective in European populations(78.3% vs 67.7%;P = 0.05).Incidence of SE was lower in LA therapy than QT(OR:0.39;95% CI:0.18-0.85;P = 0.02).A higher rate of side effects was reported in Asian patients who received QT.Our findings support the use of 10-d LA as a simple second-line treatment for H.pylori eradication with an excellent eradication rate and tolerability.The optimal second-line alternative scheme might differ among countries depending on quinolone resistance.展开更多
Gastric cancer and cancer of the gastro-oesophageal junction(GOJ) are the 4th most common cancer diagnoses worldwide with regional differences in incidence rates.The treatment of gastric and GOJ cancers is complex and...Gastric cancer and cancer of the gastro-oesophageal junction(GOJ) are the 4th most common cancer diagnoses worldwide with regional differences in incidence rates.The treatment of gastric and GOJ cancers is complex and requires multimodality treatment including chemotherapy treatment,surgery,and radiotherapy.During the past decade considerable improvements were achieved by advanced surgical techniques,tailored chemotherapies/radiotherapy and technical innovations in clinical diagnostics.In patients with advanced or metastatic gastric/GOJ cancer systemic chemotherapy with fluoropyrimidine/platinum-based regimens(+/-human epidermal growth factor receptor-2 antibody) is the mainstay of treatment.Despite these improvements,the clinical outcome for patients with advanced or metastatic disease is generally poor with 5-year survival rates ranging between 5%-15%.These poor survival rates may to some extent be related that standard therapies beyond first-line therapies have never been defined.Considering that this patient population is often not fit enough to receive further treatments there is an increasing body of evidence from phase-2 studies that in fact second-line therapies may have a positive impact in terms of overall survival.Moreover two recently published phase-3 studies support the use of second-line chemotherapy.A South Korean study compared either,irinotecan or docetaxel with best supportive care and a German study compared irinotecan with best supportive care-both studies met their primary endpoint overall survival.In this "Field of Vision" article,we review these recently published phase-3 studies and put them into the context of clinical prognostic factors helping to guide treatment decisions in patients who most likely benefit.展开更多
AIM: To study the effectiveness of second-linetreatments for advancer gastric cancer by application of Bayesian network meta-analysis.METHODS: Our search covered the literature up to February 2015. The following 6 tre...AIM: To study the effectiveness of second-linetreatments for advancer gastric cancer by application of Bayesian network meta-analysis.METHODS: Our search covered the literature up to February 2015. The following 6 treatments were evaluated:(1) irinotecan(camptothecins);(2) paclitaxel(taxanes class);(3) docetaxel(taxanes);(4) everolimus(mammalian target of rapamycin inhibitors);(5) ramucirumab(vascular endothelial growth factor receptor 2 inhibitors);(6) ramucirumab + paclitaxel. Our methodology was based on standard models of Bayesian network meta-analysis. The reference treatment was best supportive care(BSC). The endpoint was overall survival. Median survival was the outcome measure along with 95% credible intervals. RESULTS: Our search identified a total of 7 randomized controlled trials. These trials included 2298 patients(in 15 treatment arms) in whom a total of 6 active treatments were evaluated as well as BSC. There were 21 head-to-head comparisons(6 direct, 15 indirect). The difference in survival between each of two active treatments(paclitaxel and ramucirumab + paclitaxel) vs BSC was statistically significant, while the other 4 showed no statistical difference. In the 6 head-to-head comparisons between active treatments, no significant survival difference was demonstrated. CONCLUSION: Our results indicate that both paclitaxel monotherapy and ramucirumab + paclitaxel determine a significant prolongation in survival as compared with BSC.展开更多
AIM:To investigate second-line chemotherapy in gemcitabine-pretreated patients with advanced or metastatic pancreatic cancer [(frequency,response,outcome,course of carbohydrate antigen 19-9 (CA 19-9)].METHODS:This ret...AIM:To investigate second-line chemotherapy in gemcitabine-pretreated patients with advanced or metastatic pancreatic cancer [(frequency,response,outcome,course of carbohydrate antigen 19-9 (CA 19-9)].METHODS:This retrospective study included all patients with advanced or metastatic pancreatic cancer (adenocarcinoma or carcinoma) treated with secondline chemotherapy in our center between 2000 and 2008.All patients received first-line chemotherapy with gemcitabine,and prior surgery or radiotherapy was permitted.We analyzed each chemotherapy protocol for second-line treatment,the number of cycles and the type of combination used.The primary endpoint was overall survival.Secondary endpoints included progression-free survival,response rate,grade 3-4 toxicity,dosage modifications and CA 19-9 course.RESULTS:A total of eighty patients (38%) underwenta second-line therapy among 206 patients who had initially received first-line treatment with a gemcitabine-based regimen.Median number of cycles was 4 (range:1-12) and the median duration of treatment was 2.6 mo (range:0.3-7.4).The overall disease control rate was 40.0%.The median overall survival and progression-free survival from the start of second-line therapy were 5.8 (95% CI:4.1-6.6) and 3.4 mo (95% CI:2.4-4.2),respectively.Toxicity was generally acceptable.Median overall survival of patients with a CA 19-9 level declining by more than 20% was 10.3 mo (95% CI:4.5-11.6) vs 5.2 mo (95% CI:4.0-6.4) for others (P=0.008).CONCLUSION:A large proportion of patients could benefit from second-line therapy,and CA 19-9 allows efficient treatment monitoring both in first and secondline chemotherapy.展开更多
Objective: Panitumumab administered as monotherapy in colorectal cancer(CRC) has shown response and disease stabilization rates of approximately 30%. The current study aimed to evaluate the progression-free survival(P...Objective: Panitumumab administered as monotherapy in colorectal cancer(CRC) has shown response and disease stabilization rates of approximately 30%. The current study aimed to evaluate the progression-free survival(PFS) and overall survival(OS) of patients with metastatic colorectal cancer(mCRC) treated with panitumumab every 3 weeks as a second line treatment.Methods: This study is a retrospective analysis of 18 patients, aged more than 18 years, with wild-type KRAS exon 2 mCRC treated with panitumumab as a second-line single agent after progression on first-line chemotherapy.Results: The median number of courses received was 10(range, 4-29), and the median duration of treatment was 30 weeks(range,12-96 weeks). After a median follow-up period of 13 months, the median PFS was 6 months(range, 4.3-7.7 months) and the median OS was 11 months(range, 7.4-14.5 months). The median PFS was 4 months for patients with < grade 2 skin toxicity and 6months(range, 4.5-7.5 months) for patients with ≥ grade 2 skin rash(P=0.05). The median OS was 9 months(range, 6.4-11.5months) and 14 months(range, 11.6-16.3 months) for the two groups of patients(P=0.002).Conclusions: Panitumumab given every 3 weeks is effective and well tolerated in patients with advanced CRC that progressed after standard chemotherapy.展开更多
文摘Objective:Paclitaxel(P)is a standard second-line chemotherapy in the treatment of advanced gastric cancer.This study compared the clinical outcome of a paclitaxel plus raltitrexed(RP)regimen as second-line treatment in metastatic gastric cancer(MGC)patients.Methods:An open,randomized,multi-center phase Ⅱ clinical trial was conducted involving 148 patients who were randomly assigned and treated with RP[raltitrexed(3 mg/m^(2)on day 1)and paclitaxel(135 mg/m^(2)on day 1 every 3 weeks)]or P[paclitaxel(135 mg/m^(2)on day 1 every 3 weeks)]as 2nd-line chemotherapy.The primary endpoint was progression-free survival(PFS).The secondary endpoints were the overall response rate(ORR),overall survival(OS),and safety.Results:PFS had a tendency to be prolonged with RP compared to P(2.7 months vs.1.7 months;P=0.148).OS was also prolonged with RP compared to P(10.2 months vs.6.1 months;P=0.140).The ORR was equal in the RP and P groups(6.8%and 4.0%;P=0.72).The disease control rate(DCR)in the RP and P groups was 56.2%and 36.0%,respectively.Grade 3-4 treatment-related adverse events occurred in 36.2%(RP)and 28.2%(P)of patients.Frequent grade 3-4 toxicities for RP and P were neutropenia(11.0%and 4.0%),anemia(1.4%and 4.0%),and thrombocytopenia(1.4%and 5.3%),and all grades of peripheral neurotoxicity(12.3%vs.17.3%).All grades of hepatic toxicity were demonstrated for the RP and P groups based on elevated aminotransferase levels(27.4%and 14.1%).Subgroup analysis shows if MGC was combined with ascites or peritoneal involvement,the OS of the RP regimen was longer(P=0.05).Conclusions:Second-line palliative chemotherapy with RP was shown to prolong the PFS and OS,especially among patients with ascites or peritoneal involvement,which warrants confirmation using larger sample studies.
文摘Gastric cancer remains one among the leading causes of cancer-related deaths, regardless of its decreasing incidence and newly available treatment options. Most patients present at an advanced stage and are treated with upfront systemic chemotherapy. Those patients receiving first-line therapy may initially respond to treatment, but many of them relapse over time. In such condition, second-line treatment for disease progression remains the only available option. Although there exists no standard approach in the second-line setting, several phase Ⅲ trials have shown modest survival benefit in patients receiving irinotecan, taxane and ramucirumab over the best supportive care or active agents. This review analyzes the currently available treatment regimens and future directions of research in the second-line setting for metastatic gastric cancer with the best available evidence. Additionally, the prognostic factors that influence patient survival in those receiving second-line therapy are discussed.
文摘AIM: To compare the efficacy of 14- and 7-d bismuthbased quadruple therapies as second-line eradication treatment for Helicobacter pylori(H.pylori) infection.METHODS: Between 2004 and 2014,the medical records of 790 patients who had experienced failure of first-line proton pump inhibitor(PPI)-based eradication therapy and were then treated with bismuth-based quadruple therapy were retrospectively reviewed.Those who received bismuth-based quadruple therapy [PPI,bismuth,metronidazole,and tetracycline(PBMT)] for either 7 d or 14 d were assigned to a PBMT-7 group(n = 543) or a PBMT-14 group(n = 247),respectively.The eradication rates for both groups were determined by intention-to-treat(ITT) and per-protocol(PP) analyses.ITT analysis compared the treatment groups as originally allocated while the PP analysis including only those patients who had completed the treatment as originally allocated.Successful eradication therapy for H.pylori infection was defined as a negative 13C-urea breath test 4 wk after the end of eradication treatment.RESULTS: The overall ITT eradication rate was 69.1%(546/790).Final ITT eradication rates were 67.4%(366/543; 95%CI: 63.1%-71.7%) in the PBMT-7 group and 72.8%(180/247; 95%CI: 67.4%-78.2%) in the PBMT-14 group(P = 0.028).The overall PP eradication rate was 80.0%(546/682),and the final PP eradication rates were 78.2%(366/468; 95%CI: 72.1%-84.0%) in the PBMT-7 group and 84.1%(180/214; 95%CI: 76.8%-90.8%) in the PBMT-14 group(P = 0.009).The H.pylori eradication rates in the PBMT-14 group weresignificantly higher than in the PBMT-7 group according to both ITT(P = 0.028) and PP analysis(P = 0.009).Compliance was similar in both groups(PBMT-7 group: 97.9%; PBMT-14 group: 96.4%).Adverse event rates were 10.7%(51/478) and 17.1%(38/222) in the PBMT-7 and PBMT-14 groups,respectively(P = 0.487).CONCLUSION: The 14-d bismuth-based quadruple therapy is a significantly more effective second-line eradication treatment for H.pylori infection than the 7-d alternative.
文摘BACKGROUND The standard management of autoimmune hepatitis(AIH)is based on corticosteroids,alone or in combination with azathioprine.Second-line treatments are needed for patients who have refractory disease.However,high-quality data on the alternative management of AIH are scarce.AIM To evaluate the efficacy and safety of tacrolimus and mycophenolate mofetil(MMF)and the quality of evidence by using the Grading of Recommendations Assessment,Development and Evaluation approach(GRADE).METHODS A systematic review and meta-analysis of the available data were performed.We calculated pooled event rates for three outcome measures:Biochemical remission,adverse events,and mortality,with their corresponding 95%confidence intervals(CI).RESULTS The pooled biochemical remission rate was 68.9%(95%CI:60.4-76.2)for tacrolimus,and 59.6%(95%CI:54.8-64.2)for MMF,and rates of adverse events were 25.5%(95%CI:12.4-45.3)for tacrolimus and 24.1%(95%CI:15.4-35.7)for MMF.The pooled mortality rate was estimated at 11.5%(95%CI:7.1-18.1)for tacrolimus and 9.01%(95%CI:6.2-12.8)for MMF.Pooled biochemical remission rates for tacrolimus and MMF in patients with intolerance to standard therapy were 56.6%(CI:43.4-56.6)vs 73.5%(CI:58.1-84.7),and among non-responders were 59.1%(CI:48.7-68.8)vs 40.8%(CI:32.3-50.0),respectively.Moreover,the overall quality assessments using GRADE proved to be very low for all our outcomes in both treatment groups.CONCLUSION Tacrolimus and MMF are in practice considered effective for patients with AIH who are non-responders or intolerant to first-line treatment,but we found no high-quality evidence to support this statement.
基金funding from Chugai Pharmaceutical Co.Ltd.Roche Korea Co.Ltd.Roche Shanghai.Co.Ltd
文摘Background: Capecitabine and irinotecan combination therapy(XELIRI) has been examined at various dose levels to treat metastatic colorectal cancer(m CRC). Recently, in the Association of Medical Oncology of the German Cancer Society(AIO) 0604 trial, tri?weekly XELIRI plus bevacizumab, with reduced doses of irinotecan(200 mg/m^2 on day 1) and capecitabine(1600 mg/m^2 on days 1–14), repeated every 3 weeks, has shown favorable tolerability and eicacy which were comparable to those of capecitabine and oxaliplatin(XELOX) plus bevacizumab. The doses of capecit?abine and irinotecan in the AIO trial are considered optimal. In a phase I/II study, XELIRI plus bevacizumab(BIX) as second?line chemotherapy was well tolerated and had promising eicacy in Japanese patients.Methods: The Asian XELIRI Projec T(AXEPT) is an East Asian collaborative, open?labelled, randomized, phase Ⅲ clinical trial which was designed to demonstrate the non?inferiority of XELIRI with or without bevacizumab versus standard FOLFIRI(5?fluorouracil, leucovorin, and irinotecan combination) with or without bevacizumab as second?line chemo?therapy for patients with m CRC. Patients with 20 years of age or older, histologically conirmed m CRC, Eastern Coop?erative Oncology Group performance status 0–2, adequate organ function, and disease progression or intolerance of the irst?line regimen will be eligible. Patients will be randomized(1:1) to receive standard FOLFIRI with or with?out bevacizumab(5 mg/kg on day 1), repeated every 2 weeks(FOLIRI arm) or XELIRI with or without bevacizumab(7.5 mg/kg on day 1), repeated every 3 weeks(XELIRI arm). A total of 464 events were estimated as necessary to show non?inferiority with a power of 80% at a one?sided α of 0.025, requiring a target sample size of 600 patients. The 95% conidence interval(CI) upper limit of the hazard ratio was pre?speciied as less than 1.3.Conclusion: The Asian XELIRI Projec T is a multinational phase III trial being conducted to provide evidence for XELIRI with or without bevacizumab as a second?line treatment option of mCRC.
文摘Dasatinib is a second-generation tyrosine kinase inhibitor (TKI)and it could be used as a second-line treatment for patients with chronic myeloid leukemia (CML).Yinishu,a generic dasatinib made in China,was approved by the China Food and Drug Administration in 2013 and it costs much less than the patented dasatinib SPRYCEL.The present study aimed to examine the efficacy and safety of Yinishu as a second-line treatment for CML by comparing the baseline clinical characteristics,rates of adverse events and efficacy between Yinishu and SPRYCEL groups. The results showed that there were no significant differences in the rates of optimal response between Yinishu and SPRYCEL for patients who started second-line treatment because of treatment failure.For patients who started second-line treatment because of intolerance of first-line treatment, their levels of BCR-ABL1/ABL1 on the international scale (BCR-ABL^IS)was maintained very low throughout the course of Yinishu treatment.Drug-related adverse events occurred with the same frequency in these two groups.It was confirmed that Yinishu was effective and safe as a second- line treatment for CML patients.Yinishu may be more suitable for patients who are economically unable to pay for the patented dasatinib SPRYCEL.
文摘AIM: To evaluate the efficacy of the 14-d moxifloxacinbased triple therapy for the second-line eradication of Helicobacter pylori(H. pylori) infection.METHODS: Between 2011 and 2013, we conducted a retrospective review of the medical records of 160 patients who had experienced failure of their first-line proton pump inhibitor-based eradication therapy and subsequently received the moxifloxacin-based triple therapy as a second-line eradication treatment regimen. The patients who were treated with the moxifloxacinbased triple therapy(oral 20 mg rabeprazole b.i.d., 1000 mg amoxicillin b.i.d., and 400 mg moxifloxacin q.d.) for 7 d were assigned to the RAM-7 group(n = 79) while those who took them for 14 days were assigned to RAM-14 group(n = 81). The eradication rates for both groups were determined by intentionto-treat(ITT) and per-protocol(PP) analyses. ITT analysis compared the treatment groups as originally allocated while the PP analysis including only those patients who had completed the treatment as originally allocated. Successful eradication therapy for H. pylori infection was defined as the documentation of a negative 13C-urea breath test 4 wk after the end of the eradication treatment.RESULTS: The overall ITT eradication rate was 76.2%(122/160). The final ITT eradication rates were 70.8%(56/79; 95%CI: 63.3%-77.1%) in the RAM-7 group and 81.4%(66/81; 95%CI: 74.6%-88.3%) in the RAM-14 group(P = 0.034). The overall PP eradication rate was 84.1%(122/145), and the final PP eradication rates were 77.7%(56/72; 95%CI: 70.2%-85.3%) in the RAM-7 group and 90.4%(66/73; 95%CI: 82.8%-98.1%) in the RAM-14 group(P = 0.017). The H. pylori-eradication rates in the RAM-14 group were significantly higher compared with that of the RAM-7 group according to both the ITT(P = 0.034) and the PP analyses(P = 0.017). Both groups exhibited good treatment compliance(RAM-7/RAM-14 group: 100%/100%). The adverse event rates were19.4%(14/72)and 20.5%(15/73)in the RAM-7 and RAM-14 groups,respectively(P=0.441).Adverse events occurred in 14 of the 72 patients(19.4)in the RAM-7 group and in 15 of the 73 patients(20.5)in the RAM-14 group.No statistically significant differences(P=0.441)were observed.CONCLUSION:The 14-d moxifloxacin-based triple therapy is a significantly more effective secondline eradication treatment as compared to the 7-d alternative for H.pylori infection in South Korea.
文摘Over the past ten years,sorafenib,a multikinase inhibitor,has been the standard of care for patients with unresectable hepatocellular carcinoma(HCC)and wellpreserved liver function.Recently,lenvatinib,a different multikinase inhibitor,was shown to be non-inferior to sorafenib,in terms of survival,while all other agents previously tested failed to prove non-inferiority(or superiority)when compared to sorafenib.Similarly,in the second-line setting,most investigational drugs failed to provide better survival outcomes than placebo.However,in the last 2 years three positive phase III trials have been published in this setting.The RESORCE trial,a phase III study evaluating regorafenib in HCC patients who experienced disease progression after first-line treatment with sorafenib,showed better outcomes with regorafenib compared to placebo.More recently,the phase III CELESTIAL trial demonstrated the superiority of cabozantinib,a multikinase inhibitor targeting vascular endothelial growth factor receptor,MET,and AXL,vs placebo in the second-and third-line setting in patients progressing on or intolerant to sorafenib.The survival benefits of a sustained anti-angiogenic inhibition were demonstrated also with ramucirumab in the phase III REACH-2 trial in patients previously treated with sorafenib and who had high baseline alpha-fetoprotein levels.Overall,the adverse events reported in these trials were in line with the known safety profiles of the tested agents.After nearly a decade of a certain degree of stagnation,we are now witnessing a period of novel therapeutic advances with multikinase inhibitors and monoclonal antibodies that will likely change the treatment scenario of HCC.
文摘BACKGROUND There is no standard therapy for second-line treatment of gemcitabine-refractory pancreatic cancer patients with poor performance status.A combination of chemotherapy drugs 5-fluorouracil(5-FU),leucovorin,irinotecan,and oxaliplatin(FOLFIRINOX)or 5-fluorouracil/leucovorin plus nanoliposomal irinotecan can be considered as second-line treatment for such patients;however,due to toxicity,none of the regimens are recommended for patients with poor performance.Capecitabine or S-1 has relatively low toxicity and can be considered a treatment option for gemcitabine-refractory pancreatic cancer.AIM To investigate the efficacy and toxicity of oral chemotherapy as second-line treatment in patients with pancreatic cancer.METHODS Patients who had progressive disease after first-line gemcitabine-based chemotherapy were retrospectively analyzed between January 2011 and December 2018.They were treated with capecitabine or S-1 as the second-line treatment.Capecitabine was administered as a 2500 mg/m2 divided dose on days 1-14,followed by a 1-wk rest.S-1 was taken orally based on the patient’s body surface area for 28 d,followed by 2-wk of rest.Progression-free survival and overall survival were used to compare efficacy of capecitabine and S-1.RESULTS Of the 81 patients,41 were treated with capecitabine and 40 with S-1.The median time to treatment failure in both groups was 1.5 mo(P=0.425).The objective response rate was similar in the two groups:9.8%with capecitabine and 2.5%with S-1(P=0.359).Median progression-free survival was longer in the S-1 group than in the capecitabine group(S-12.7 mo,capecitabine 2.0 mo,P=0.003).There was no significant difference in the median overall survival between the capecitabine and S-1 groups(4.3 mo vs 5.0 mo,P=0.092).Grade 3 or 4 hand-foot syndrome was significantly more common in the capecitabine group than in the S-1 group(14.6%vs 0%,P=0.026).CONCLUSION Capecitabine or S-1 can be used as a second-line treatment for patients with advanced pancreatic cancer with poor performance status after progression to a gemcitabine-based regimen.
基金Capital Clinical Medicine Special Project(No.Z181100001718215)National Natural Science Foundation of China(No.81602314).Research number:CSCO-BC RWS 16002。
文摘Objective:Several studies have demonstrated different benefits for patients whose disease progressed despite previous trastuzumab treatment.Due to limited real-world data,we evaluate the effectiveness of anti-human epidermal growth factor receptor 2(HER2)therapy(lapatinib or trastuzumab)plus chemotherapy or chemotherapy alone in patients who were previously treated with trastuzumab-containing regimens and investigate factors associated with effectiveness.And we further show the effectiveness of the two anti-HER2 therapy groups.Methods:A total of 342 HER2-positive metastatic breast cancer(MBC)patients whose disease progressed during prior anti-HER2(trastuzumab)and standard chemotherapy therapy from Department of Breast Oncology,the Fifth Medical Center of Chinese PLA General Hospital,from August 2010 to December 2016 were included.Seventy-eight patients received standard chemotherapy only,148 patients continued to receive trastuzumab and switched to other chemotherapy drugs,and 116 patients received tyrosine-kinase inhibitors(TKIs;lapatinib)and chemotherapy.The main outcome measures were progression-free survival(PFS),overall response rate(ORR),and clinical benefit rate(CBR).Subgroup analyses were conducted to identify patient characteristics associated with the greatest clinical benefit.Results:After a median follow-up of 26.2(range,2.0-56.0)months,PFS significantly improved with anti-HER2 therapy compared with chemotherapy alone:median 6.0 months with lapatinib[95%confidence interval(95%CI),4.53-7.47],4.5 months with trastuzumab(95%CI,3.99-5.01)vs.3.0 months with chemotherapy alone(95%CI,2.42-3.58);stratified hazard ratio(HR)=0.70,95%CI,0.60-0.81;P<0.0001.The ORR values were 33.6%,25.0%and 12.8%,respectively,the CBR values were 60.3%,48.6%and 26.9%,respectively.The effectiveness of lapatinib group and trastuzumab group were further analyzed.In multivariate analysis,lapatinib group was associated with a longer PFS,after controlling other potential confounders(HR=0.68,95%CI,0.52-0.90;P=0.006).Conclusions:The combination of TKIs and chemotherapy was effective in this cohort previously treated with trastuzumab treatment.Therefore,TKIs combined with chemotherapy is an option for Chinese HER2-positive MBC patients previously treated with trastuzumab treatment.
文摘Aims and Background: Irinotecan is a standard option for relapsed/refractory advanced colo- rectal cancer. Combination with raltitrexed and irinotecan at lower than MTD doses should preserve disease stabilisation while decreasing toxicity. Patients and Methods: From January 2004 to April 2009, we analyzed, retrospectively, our data on irinotecan + raltitrexed, fixed doses, as a second-line chemotherapy in elderly pa- tients (>70 years) with advanced colorectal can- cer after failure of oxaliplatin based chemothera- py twenty-three patients were evaluated. Iri- notecan 350 mg + raltitrexed 2.6 mg were given every 3 weeks. Tumo r measurements were ob- tained after every third course of therapy. Toxic- ity was assessed weekly using the National Cancer Institute Common Toxicity Criteria, ver- sion 2. Results: The median number of treatment courses received per patient was 4 (range, 1 - 8). All pa-tients were assessable for toxicity and 21 for response. The most frequently observed severetoxicities were diarrhea (grade 2, 13%) No cases of significant neutropenia occurred. Ob- jective partial responses were observed in 3 pa- tients (13%). An additional 10 patients (43%) had stable disease as their best response. To date, 12 patients have progressed with a median time- to-progression of 4.3 months and a median sur- vival of 8.3 months. Conclusions: A three weekly irinotecan + raltitrexed administration can indu- ce tumor control in elderly patients with advanc- ed colorectalcancer that has progressed during or shortly after oxaliplatin-based chemotherapy. The diarrhea by irinotecan, seems mitigated by coad-ministration of a smaller dose of
文摘Hepatocellular carcinoma(HCC)is the most frequently diagnosed primary tumor of the liver and is usually detected as advanced disease.It is an aggressive disease that often progresses rapidly when it fails to respond to treatment.As such,patients have limited opportunities to try different subsequent-line treatment regimens.In the last 5 years,the number of agents and/or regimens available for the treatment of advanced HCC has significantly increased,which has made treatment choices for this patient population increasingly complex.In the secondline setting,several phase III trials of regorafenib(RESORCE),ramucirumab(REACH/REACH-2),and cabozantinib(CELESTIAL)have demonstrated clinically meaningful survival benefits in patients with the disease.However,the median overall survival of patients with advanced HCC remains unchanged at approximately 12 mo from the start of systemic second-line therapy,with a limited duration of response.Evidence from the REACH/REACH-2 trials demonstrated for the first time that baseline alpha-fetoprotein(AFP)levels can be used as an identification factor to select those who are likely to benefit the most from ramucirumab treatment.Ramucirumab is both well tolerated and efficacious and has a clinically acceptable safety profile.Therefore,it should be considered an option for patients with AFP levels≥400 ng/mL.
文摘Aim: To investigate the efficacy and tolerability of second-line metronidazole triple therapy with vonoprazan (VPZ) for Helicobacter pylori (H. pylori). Methods: We retrospectively reviewed medical records of patients who experienced clarithromycin triple therapy failure and were treated with second-line (20 mg VPZ (n = 274)/30 mg lansoprazole (n = 323) or 10 mg rabeprazole (n = 141) twice daily, 750 mg amoxicillin twice daily, 250 mg metronidazole twice daily for 7 days) eradication therapies. Successful eradication rates were compared between two groups: those receiving VPZ and those receiving a proton pump inhibitor (PPI). Adverse events were also investigated. Results: Successful second-line eradication rates according to ITT analysis and PP analysis, respectively, were 79.9% and 92.4% for VPZ therapy and 83.6% and 93.3% for PPI therapy. There were no significant differences between treatment groups. The eradication rates in those who had received first-line VPZ therapy previously according to ITT and PP analysis were 75.2% and 88.1%, respectively;in contrast, values were 82.5% and 95.4%, respectively, for those who had received first-line PPI therapy previously. In second-line therapy, the overall adverse event rate for VPZ therapy was the same as for PPI therapy. Conclusions: The efficacy and tolerability of metronidazole-containing second-line triple therapy with VPZ or a PPI were equivalent.
文摘Despite extensive clinical research in non-small cell lung cancer (NSCLC), overall survival is still poor. Racotumomab-alum is an anti-idiotypic cancer vaccine that targets NeuGcGM3 tumor associated ganglioside. The aim of this study was to evaluate safety and efficacy of racotumomab-alum in advanced NSCLC patients with progressive disease. This expanded access program included 86 histologically confirmed NSCLC patients, 18 years or older age, with advanced disease and without therapeutic option, with ECOG performance status ≤3, adequate organ functions and signed informed consent. The primary endpoint was overall survival and toxicity was measure assessed treatment-related toxicity according CTCAEv3. The study was approved by ethical review boards of participant institutions. Racotumomab-alum treatment consisted in 5 biweekly intradermal doses (1 mg/mL) during the induction phase of treatment (2 months). The maintenance phase consisted in monthly re-immunizations until unacceptable toxicity or PS worsening. The median overall survival time of all patients treated with racotumomab-alum was 8.96 months. The survival rates at 12 and 24 months were 42.8% and 28.0%, respectively. Patients that completed the induction phase of treatment (five doses or more) reached a median OS of 12.1 months. The most common adverse events were injection site reaction, bone pain, cough and asthenia. Racotumomab-alum cancer vaccine could be considered an effective and safe treatment option as second-line therapy for advanced NSCLC. Further clinical studies should be conducted to confirm this result.
文摘Background: Methotrexate, vinblastine, doxorubicin, and cisplatin regimen, and gemcitabine and cisplatin regimen are widely used for advanced or metastatic urothelial carcinomas (UCs). However, a standard treatment for patients who fail these firstline chemotherapies is unavailable. We examined the efficacy and safety of secondline paclitaxel, gemcitabine, and cisplatin (PCG) chemotherapy in Japanese patients. Methods: Between 2004 and 2010, 25 patients with metastatic UCs who failed to respond to platinumbased regimens were treated with PCG. They received intravenous paclitaxel (60 mg/m2) and gemcitabine (1000 mg/m2) on days 1 and 8, and cisplatin (70 mg/m2) on day 2 of every 21 day course. We retrospectively collected patients’ clinical and pathological data and evaluated adverse effects and survivals. Results: Patients underwent 95 PCG cycles in all (average, 3.8 cycles per patient). One patient (4%) achieved complete response, 5 (20%) showed partial response, 8 (42%) had disease stabilization, and 5 (26%) had disease progression. Median overall survival was 8.5 months. Neutropenia and thrombocytopenia of grade ≥ 3 were observed in 68% and 56% of patients, respectively. No treatment related death occurred. Multivariate analysis revealed that hemoglobin levels 1.73 m2) were significant risk factors for overall survival. Conclusion: PCG chemotherapy in the secondline setting potentially contributed to good prognosis in selected patients with relatively significant but tolerable toxicity.
文摘Worldwide prevalence of Helicobacter pylori(H.pylori) infection is approximately 50%,with the highest being in developing countries.We compared cure rates and tolerability(SE) of second-line anti-H.pylori levofloxacin/amoxicillin(LA)-based triple regimens vs standard quadruple therapy(QT).An English language literature search was performed up to October 2010.A meta-analysis was performed including randomized clinical trials comparing 7-or 10-d LA with 7-d QT.In total,10 articles and four abstracts were identified.Overall eradication rate in LA was 76.5%(95% CI:64.4%-97.6%).When only 7-d regimens were included,cure rate was 70.6%(95% CI:40.2%-99.1%),whereas for 10-d combinations,cure rate was significantly higher(88.7%;95% CI:56.1%-109.9%;P < 0.05).Main eradication rate for QT was 67.4%(95% CI:49.7%-67.9%).The 7-d LA and QT showed comparable efficacy [odds ratio(OR):1.09;95% CI:0.63-1.87],whereas the 10-d LA regimen was significantly more effective than QT(OR:5.05;95% CI:2.74-9.31;P < 0.001;I 2 = 75%).No differences were reported in QT eradication rates among Asian and European studies,whereas LA regimens were more effective in European populations(78.3% vs 67.7%;P = 0.05).Incidence of SE was lower in LA therapy than QT(OR:0.39;95% CI:0.18-0.85;P = 0.02).A higher rate of side effects was reported in Asian patients who received QT.Our findings support the use of 10-d LA as a simple second-line treatment for H.pylori eradication with an excellent eradication rate and tolerability.The optimal second-line alternative scheme might differ among countries depending on quinolone resistance.
文摘Gastric cancer and cancer of the gastro-oesophageal junction(GOJ) are the 4th most common cancer diagnoses worldwide with regional differences in incidence rates.The treatment of gastric and GOJ cancers is complex and requires multimodality treatment including chemotherapy treatment,surgery,and radiotherapy.During the past decade considerable improvements were achieved by advanced surgical techniques,tailored chemotherapies/radiotherapy and technical innovations in clinical diagnostics.In patients with advanced or metastatic gastric/GOJ cancer systemic chemotherapy with fluoropyrimidine/platinum-based regimens(+/-human epidermal growth factor receptor-2 antibody) is the mainstay of treatment.Despite these improvements,the clinical outcome for patients with advanced or metastatic disease is generally poor with 5-year survival rates ranging between 5%-15%.These poor survival rates may to some extent be related that standard therapies beyond first-line therapies have never been defined.Considering that this patient population is often not fit enough to receive further treatments there is an increasing body of evidence from phase-2 studies that in fact second-line therapies may have a positive impact in terms of overall survival.Moreover two recently published phase-3 studies support the use of second-line chemotherapy.A South Korean study compared either,irinotecan or docetaxel with best supportive care and a German study compared irinotecan with best supportive care-both studies met their primary endpoint overall survival.In this "Field of Vision" article,we review these recently published phase-3 studies and put them into the context of clinical prognostic factors helping to guide treatment decisions in patients who most likely benefit.
文摘AIM: To study the effectiveness of second-linetreatments for advancer gastric cancer by application of Bayesian network meta-analysis.METHODS: Our search covered the literature up to February 2015. The following 6 treatments were evaluated:(1) irinotecan(camptothecins);(2) paclitaxel(taxanes class);(3) docetaxel(taxanes);(4) everolimus(mammalian target of rapamycin inhibitors);(5) ramucirumab(vascular endothelial growth factor receptor 2 inhibitors);(6) ramucirumab + paclitaxel. Our methodology was based on standard models of Bayesian network meta-analysis. The reference treatment was best supportive care(BSC). The endpoint was overall survival. Median survival was the outcome measure along with 95% credible intervals. RESULTS: Our search identified a total of 7 randomized controlled trials. These trials included 2298 patients(in 15 treatment arms) in whom a total of 6 active treatments were evaluated as well as BSC. There were 21 head-to-head comparisons(6 direct, 15 indirect). The difference in survival between each of two active treatments(paclitaxel and ramucirumab + paclitaxel) vs BSC was statistically significant, while the other 4 showed no statistical difference. In the 6 head-to-head comparisons between active treatments, no significant survival difference was demonstrated. CONCLUSION: Our results indicate that both paclitaxel monotherapy and ramucirumab + paclitaxel determine a significant prolongation in survival as compared with BSC.
文摘AIM:To investigate second-line chemotherapy in gemcitabine-pretreated patients with advanced or metastatic pancreatic cancer [(frequency,response,outcome,course of carbohydrate antigen 19-9 (CA 19-9)].METHODS:This retrospective study included all patients with advanced or metastatic pancreatic cancer (adenocarcinoma or carcinoma) treated with secondline chemotherapy in our center between 2000 and 2008.All patients received first-line chemotherapy with gemcitabine,and prior surgery or radiotherapy was permitted.We analyzed each chemotherapy protocol for second-line treatment,the number of cycles and the type of combination used.The primary endpoint was overall survival.Secondary endpoints included progression-free survival,response rate,grade 3-4 toxicity,dosage modifications and CA 19-9 course.RESULTS:A total of eighty patients (38%) underwenta second-line therapy among 206 patients who had initially received first-line treatment with a gemcitabine-based regimen.Median number of cycles was 4 (range:1-12) and the median duration of treatment was 2.6 mo (range:0.3-7.4).The overall disease control rate was 40.0%.The median overall survival and progression-free survival from the start of second-line therapy were 5.8 (95% CI:4.1-6.6) and 3.4 mo (95% CI:2.4-4.2),respectively.Toxicity was generally acceptable.Median overall survival of patients with a CA 19-9 level declining by more than 20% was 10.3 mo (95% CI:4.5-11.6) vs 5.2 mo (95% CI:4.0-6.4) for others (P=0.008).CONCLUSION:A large proportion of patients could benefit from second-line therapy,and CA 19-9 allows efficient treatment monitoring both in first and secondline chemotherapy.
文摘Objective: Panitumumab administered as monotherapy in colorectal cancer(CRC) has shown response and disease stabilization rates of approximately 30%. The current study aimed to evaluate the progression-free survival(PFS) and overall survival(OS) of patients with metastatic colorectal cancer(mCRC) treated with panitumumab every 3 weeks as a second line treatment.Methods: This study is a retrospective analysis of 18 patients, aged more than 18 years, with wild-type KRAS exon 2 mCRC treated with panitumumab as a second-line single agent after progression on first-line chemotherapy.Results: The median number of courses received was 10(range, 4-29), and the median duration of treatment was 30 weeks(range,12-96 weeks). After a median follow-up period of 13 months, the median PFS was 6 months(range, 4.3-7.7 months) and the median OS was 11 months(range, 7.4-14.5 months). The median PFS was 4 months for patients with < grade 2 skin toxicity and 6months(range, 4.5-7.5 months) for patients with ≥ grade 2 skin rash(P=0.05). The median OS was 9 months(range, 6.4-11.5months) and 14 months(range, 11.6-16.3 months) for the two groups of patients(P=0.002).Conclusions: Panitumumab given every 3 weeks is effective and well tolerated in patients with advanced CRC that progressed after standard chemotherapy.
