While an increasing number of therapeutic options are now available for the first-line treatment of locally advanced or metastatic pancreatic cancer,the optimal choice for treatment in the second-line setting and beyo...While an increasing number of therapeutic options are now available for the first-line treatment of locally advanced or metastatic pancreatic cancer,the optimal choice for treatment in the second-line setting and beyond is less well defined.A variety of cytotoxic agents,either alone or in combination,have been evaluated,although primarily in the context of small single-arm or retrospective studies.Most regimens have been associated with median progression-free survival rates in the range of 2-4 mo and overall survival rates between 4-8mo,highlighting the very poor prognosis of patients who are candidates for such treatment.Targeted therapies studied in this chemotherapy-refractory setting,meanwhile,have produced even worse efficacy results.In the current article,we review the clinical evidence for treatment of refractory disease,primarily in patients who have progressed on front-line gemcitabine-based chemotherapy.In the process,we highlight the limitations of the available data to date as well as some of the challenges in designing appropriate clinical trials in this salvage setting,including how to select an appropriate control arm given the absence of a wellestablished reference standard,and the importance of incorporating predictive biomarkers and quality of life measures whenever possible into study design.展开更多
BACKGROUND FOLFIRINOX regimen is the first-line reference chemotherapy(L1)in advanced pancreatic ductal adenocarcinoma(aPDAC).FOLFOXIRI,a schedule with a lower dose of irinotecan and no bolus 5-fluorouracil,has demons...BACKGROUND FOLFIRINOX regimen is the first-line reference chemotherapy(L1)in advanced pancreatic ductal adenocarcinoma(aPDAC).FOLFOXIRI,a schedule with a lower dose of irinotecan and no bolus 5-fluorouracil,has demonstrated efficacy and feasibility in colorectal cancer.AIM To investigate the potential clinical value of FOLFOXIRI in patients with aPDAC in routine clinical practice.METHODS Analyses were derived from all consecutive aPDAC patients treated in L1 between January 2011 and December 2017 in two French institutions,with either FOLFOXIRI(n=165)or FOLFIRINOX(n=124)regimens.FOLFOXIRI consisted of irinotecan(165 mg/m2),oxaliplatin(85 mg/m2),leucovorin(200 mg/m2)and 5-fluorouracil(3200 mg/m2 as a 48-h continuous infusion)every 2 wk.Ninety-six pairs of patients were selected through propensity score matching,and clinical outcomes of the two treatment regimens were compared.RESULTS Median overall survival was 11.1 mo in the FOLFOXIRI and 11.6 mo in the FOLFIRINOX cohorts,respectively.After propensity score matching,survival rates remained similar between the two regimens in terms of overall survival(hazard ratio=1.22;P=0.219)and progression-free survival(hazard ratio=1.27;P=0.120).The objective response rate was 37.1%in the FOLFOXIRI group vs 47.8%in the FOLFIRINOX group(P=0.187).Grade 3/4 toxicities occurred in 28.7%of patients in the FOLFOXIRI cohort vs 19.5%in the FOLFIRINOX cohort(P=0.079).FOLFOXIRI was associated with a higher incidence of grade 3/4 digestive adverse events.Hematopoietic growth factors were used after each chemotherapy cycle and the low hematological toxicity rates were below 5%with both regimens.CONCLUSION FOLFOXIRI is feasible in L1 in patients with aPDAC but does not confer any therapeutic benefit as compared with FOLFIRINOX.The low hematological toxicity rates strengthened the relevance of primary prophylaxis with hematopoietic growth factors.展开更多
AIM:To evaluate the efficacy and safety of paclitaxelnedaplatin combination as a front-line regimen in Chinese patients with metastatic esophageal squamous cell carcinoma(ESCC).METHODS:A two-center,open-label,single-a...AIM:To evaluate the efficacy and safety of paclitaxelnedaplatin combination as a front-line regimen in Chinese patients with metastatic esophageal squamous cell carcinoma(ESCC).METHODS:A two-center,open-label,single-arm phaseⅡstudy was designed.Thirty-nine patients were enrolled and included in the intention-to-treat analysis of efficacy and adverse events.Patients received 175mg/m2of paclitaxel over a 3 h infusion on 1 d,followed by nedaplatin 80 mg/m2in a 1 h infusion on 2 d every3 wk until the documented disease progression,unac-ceptable toxicity or patient’s refusal.RESULTS:Of the 36 patients assessable for efficacy,there were 2 patients(5.1%)with complete response and 16 patients(41.0%)with partial response,giving an overall response rate of 46.1%.The median progression-free survival and median overall survival for all patients were 7.1 mo(95%CI:4.6-9.7)and 12.4 mo(95%CI:9.5-15.3),respectively.Toxicities were moderate and manageable.Grade 3/4 toxicities included neutropenia(15.4%),nausea(10.3%),anemia(7.7%),thrombocytopenia(5.1%),vomiting(5.1%)and neutropenia fever(2.6%).CONCLUSION:The combination of paclitaxel and nedaplatin is active and well tolerated as a first-line therapy for patients with metastatic ESCC.展开更多
Continuous inhibition of angiogenesis beyond progression is an emerging treatment concept in the management of metastatic colorectal cancer patients with prior bevacizumab exposure. Treatment options include the conti...Continuous inhibition of angiogenesis beyond progression is an emerging treatment concept in the management of metastatic colorectal cancer patients with prior bevacizumab exposure. Treatment options include the continuation or reintroduction of bevacizumab during the second-line chemotherapy or switching to a different antiangiogenic monoclonal antibody such as aflibercept or ramucirumab. In the selection of treatment, patient-based factors such as performance status, age, tumor burden, and tolerance and sensitivity to the firstline bevacizumab-based therapy, as well as treatment-related factors such as toxicity, efficacy, and cost, should be taken into consideration.展开更多
Objective As there is currently no clear recommendation for third-line chemotherapy for small cell lung cancer(SCLC), its efficacy is unknown. To date, there have rarely been reports of Chinese patients with SCLC who ...Objective As there is currently no clear recommendation for third-line chemotherapy for small cell lung cancer(SCLC), its efficacy is unknown. To date, there have rarely been reports of Chinese patients with SCLC who received third-line chemotherapy. Therefore, we investigated the efficacy, safety, and prognostic factors of Chinese patients with SCLC treated with third-line chemotherapy.Methods A retrospective analysis of patients with SCLC who received third-line chemotherapy was performed.Results Between 2007 and 2013, 82 patients [62 men(75.6%), 20 women(24.4%); median age at the time of diagnosis, 55 years] received third-line chemotherapy at our center. Of these patients, 44 had limited-stage disease and 38 had extensive-stage disease. On third-line chemotherapy, 55(67.1%) patients had an Eastern Cooperative Oncology Group performance status(ECOG PS) of 0–1, objective response rate of 15.9%, and median overall survival after third-line chemotherapy(OS-3) and median progression-free survival after third-line chemotherapy(PFS-3) of 5.6 months and 3.0 months, respectively. On univariate analysis, PFS-3 was significantly related with ECOG PS(P = 0.005), response to second-line chemotherapy(P = 0.002), response to third-line chemotherapy(P < 0.001), and PFS after second-line chemotherapy(P = 0.026). OS-3 was significantly related with ECOG PS(P < 0.001), response to thirdline chemotherapy(P = 0.033), PFS after first-line therapy(P = 0.044), and PFS after second-line therapy(PFS-2)(P = 0.007). On multivariate analysis, ECOG PS(P = 0.008) and response to third-line chemotherapy(P = 0.046) were independent prognostic factors for PFS-3, while ECOG PS(P = 0.007) and PFS-2(P < 0.001) were independent prognostic factors for OS-3.Conclusion Few patients with SCLC receive third-line chemotherapy. Our findings suggest that patients with an ECOG PS 0–1 and PFS-2 for >3 months will be benefit from third-line chemotherapy, which should be actively offered to them.展开更多
BACKGROUND In recent years survival of patients with metastatic colorectal cancer(mCRC),though still limited,has improved significantly;clearly,when the disease becomes refractory to standard regimens,additional treat...BACKGROUND In recent years survival of patients with metastatic colorectal cancer(mCRC),though still limited,has improved significantly;clearly,when the disease becomes refractory to standard regimens,additional treatment options are needed.Studies have shown that mitomycin C(MMC),an antitumor antibiotic,and capecitabine,a precursor of 5-fluorouracil,may act synergistically in combination.The efficacy of MMC/capecitabine has been demonstrated in the first-line setting,but only a few small studies have tested it in the advanced-line setting,with contradictory results.received a median of 2 MMC/capecitabine cycles(range 0.5-9.0).Thirty-four patients(28.6%)experienced grade≥3 toxicity,including 2(1.7%)with grade 4;there was no drug-related mortality.The objective response rate was 0.8%,and the disease control rate,24.4%.Median progression-free survival(PFS)was 2.1 mo(range 0.2-20.3),and median overall survival,4.8 mo(range 0.2-27.5).The 6-month overall survival rate was 44%;8.7%of patients remained progression-free.Factors associated with longer PFS were lower gamma-glutamyl transferase level(P=0.030)and primary tumor location in the left colon(P=0.017).Factors associated with longer overall survival were lower gamma-glutamyl transferase level(P=0.022),left-colon tumor location(P=0.044),low-to-moderate histological grade(P=0.012),Eastern Cooperative Oncology Group performance status 0-1(P=0.036),and normal bilirubin level(P=0.047).CONCLUSION MMC/capecitabine is an active,available,and relatively safe regimen for use beyond standard lines of therapy in mCRC.Several clinical and laboratory parameters can identify patients more likely to benefit.展开更多
1文献来源Planchard D,Jänne PA,Cheng Y,et al.Osimertinib with or without chemotherapy in EGFR⁃mutated advanced NSCLC[J].N Engl J Med,2023,389(21):1935-1948.2证据水平1b。
[目的]评价消癌平注射液联合一线化疗治疗晚期胃癌的疗效及安全性。[方法]检索发表于中国知网(CNKI)、万方数据库(WanFang)、维普数据库(VIP)、Pubmed以及Web of science共5个中英文数据库中有关消癌平注射液联合一线化疗方案治疗晚期...[目的]评价消癌平注射液联合一线化疗治疗晚期胃癌的疗效及安全性。[方法]检索发表于中国知网(CNKI)、万方数据库(WanFang)、维普数据库(VIP)、Pubmed以及Web of science共5个中英文数据库中有关消癌平注射液联合一线化疗方案治疗晚期胃癌的随机对照试验(RCT),检索时间范围设定为各数据库自建库以来至2023年10月27日,对符合纳入排除标准的研究进行偏倚风险评价及Meta分析。[结果]共纳入10项RCT,共包含814例晚期胃癌患者;在近期疗效方面消癌平注射液联合一线化疗方案能够有效提升客观缓解率(ORR)[RR:1.35,95%CI(1.15,1.58),P=0.0002]以及卡氏评分(KPS)[RR:1.62,95%CI(1.16,2.26),P=0.005];且3-4级不良反应事件(SAE)发生数量少于单纯化疗[RR:0.32,95%CI(0.06,0.90),P=0.04];在远期生存获益方面,消癌平注射液联合一线化疗方案在无进展生存期(PFS)[HR:0.32,95%CI(0.17,0.62),P=0.0007]以及总生存期(OS)[HR:0.33,95%CI(0.16,0.65),P=0.002]方面均优于单纯化疗;GRADE分级结果显示,ORR、KPS、PFS、OS为低等级质量证据,SAE为极低等级质量证据。[结论]消癌平注射液联合一线化疗具有良好的临床疗效及安全性,但纳入文献的方法学质量较低,尚需要更加全面的大样本、多中心、随机双盲对照实验进行验证。展开更多
文摘While an increasing number of therapeutic options are now available for the first-line treatment of locally advanced or metastatic pancreatic cancer,the optimal choice for treatment in the second-line setting and beyond is less well defined.A variety of cytotoxic agents,either alone or in combination,have been evaluated,although primarily in the context of small single-arm or retrospective studies.Most regimens have been associated with median progression-free survival rates in the range of 2-4 mo and overall survival rates between 4-8mo,highlighting the very poor prognosis of patients who are candidates for such treatment.Targeted therapies studied in this chemotherapy-refractory setting,meanwhile,have produced even worse efficacy results.In the current article,we review the clinical evidence for treatment of refractory disease,primarily in patients who have progressed on front-line gemcitabine-based chemotherapy.In the process,we highlight the limitations of the available data to date as well as some of the challenges in designing appropriate clinical trials in this salvage setting,including how to select an appropriate control arm given the absence of a wellestablished reference standard,and the importance of incorporating predictive biomarkers and quality of life measures whenever possible into study design.
文摘BACKGROUND FOLFIRINOX regimen is the first-line reference chemotherapy(L1)in advanced pancreatic ductal adenocarcinoma(aPDAC).FOLFOXIRI,a schedule with a lower dose of irinotecan and no bolus 5-fluorouracil,has demonstrated efficacy and feasibility in colorectal cancer.AIM To investigate the potential clinical value of FOLFOXIRI in patients with aPDAC in routine clinical practice.METHODS Analyses were derived from all consecutive aPDAC patients treated in L1 between January 2011 and December 2017 in two French institutions,with either FOLFOXIRI(n=165)or FOLFIRINOX(n=124)regimens.FOLFOXIRI consisted of irinotecan(165 mg/m2),oxaliplatin(85 mg/m2),leucovorin(200 mg/m2)and 5-fluorouracil(3200 mg/m2 as a 48-h continuous infusion)every 2 wk.Ninety-six pairs of patients were selected through propensity score matching,and clinical outcomes of the two treatment regimens were compared.RESULTS Median overall survival was 11.1 mo in the FOLFOXIRI and 11.6 mo in the FOLFIRINOX cohorts,respectively.After propensity score matching,survival rates remained similar between the two regimens in terms of overall survival(hazard ratio=1.22;P=0.219)and progression-free survival(hazard ratio=1.27;P=0.120).The objective response rate was 37.1%in the FOLFOXIRI group vs 47.8%in the FOLFIRINOX group(P=0.187).Grade 3/4 toxicities occurred in 28.7%of patients in the FOLFOXIRI cohort vs 19.5%in the FOLFIRINOX cohort(P=0.079).FOLFOXIRI was associated with a higher incidence of grade 3/4 digestive adverse events.Hematopoietic growth factors were used after each chemotherapy cycle and the low hematological toxicity rates were below 5%with both regimens.CONCLUSION FOLFOXIRI is feasible in L1 in patients with aPDAC but does not confer any therapeutic benefit as compared with FOLFIRINOX.The low hematological toxicity rates strengthened the relevance of primary prophylaxis with hematopoietic growth factors.
基金Supported by Natural Science Foundation of Anhui Province No.070413256XMedical Research Foundation of Anhui Provincial Health Department No.2010B001 and No.13zc012
文摘AIM:To evaluate the efficacy and safety of paclitaxelnedaplatin combination as a front-line regimen in Chinese patients with metastatic esophageal squamous cell carcinoma(ESCC).METHODS:A two-center,open-label,single-arm phaseⅡstudy was designed.Thirty-nine patients were enrolled and included in the intention-to-treat analysis of efficacy and adverse events.Patients received 175mg/m2of paclitaxel over a 3 h infusion on 1 d,followed by nedaplatin 80 mg/m2in a 1 h infusion on 2 d every3 wk until the documented disease progression,unac-ceptable toxicity or patient’s refusal.RESULTS:Of the 36 patients assessable for efficacy,there were 2 patients(5.1%)with complete response and 16 patients(41.0%)with partial response,giving an overall response rate of 46.1%.The median progression-free survival and median overall survival for all patients were 7.1 mo(95%CI:4.6-9.7)and 12.4 mo(95%CI:9.5-15.3),respectively.Toxicities were moderate and manageable.Grade 3/4 toxicities included neutropenia(15.4%),nausea(10.3%),anemia(7.7%),thrombocytopenia(5.1%),vomiting(5.1%)and neutropenia fever(2.6%).CONCLUSION:The combination of paclitaxel and nedaplatin is active and well tolerated as a first-line therapy for patients with metastatic ESCC.
文摘Continuous inhibition of angiogenesis beyond progression is an emerging treatment concept in the management of metastatic colorectal cancer patients with prior bevacizumab exposure. Treatment options include the continuation or reintroduction of bevacizumab during the second-line chemotherapy or switching to a different antiangiogenic monoclonal antibody such as aflibercept or ramucirumab. In the selection of treatment, patient-based factors such as performance status, age, tumor burden, and tolerance and sensitivity to the firstline bevacizumab-based therapy, as well as treatment-related factors such as toxicity, efficacy, and cost, should be taken into consideration.
基金Supported by grants from the Jilin Health and Family Planning Commission Scientific Research Project(No.2014Z014)the "12th Five" Project of National Key Subject of New Drug Innovation(No.2013ZX09104001)
文摘Objective As there is currently no clear recommendation for third-line chemotherapy for small cell lung cancer(SCLC), its efficacy is unknown. To date, there have rarely been reports of Chinese patients with SCLC who received third-line chemotherapy. Therefore, we investigated the efficacy, safety, and prognostic factors of Chinese patients with SCLC treated with third-line chemotherapy.Methods A retrospective analysis of patients with SCLC who received third-line chemotherapy was performed.Results Between 2007 and 2013, 82 patients [62 men(75.6%), 20 women(24.4%); median age at the time of diagnosis, 55 years] received third-line chemotherapy at our center. Of these patients, 44 had limited-stage disease and 38 had extensive-stage disease. On third-line chemotherapy, 55(67.1%) patients had an Eastern Cooperative Oncology Group performance status(ECOG PS) of 0–1, objective response rate of 15.9%, and median overall survival after third-line chemotherapy(OS-3) and median progression-free survival after third-line chemotherapy(PFS-3) of 5.6 months and 3.0 months, respectively. On univariate analysis, PFS-3 was significantly related with ECOG PS(P = 0.005), response to second-line chemotherapy(P = 0.002), response to third-line chemotherapy(P < 0.001), and PFS after second-line chemotherapy(P = 0.026). OS-3 was significantly related with ECOG PS(P < 0.001), response to thirdline chemotherapy(P = 0.033), PFS after first-line therapy(P = 0.044), and PFS after second-line therapy(PFS-2)(P = 0.007). On multivariate analysis, ECOG PS(P = 0.008) and response to third-line chemotherapy(P = 0.046) were independent prognostic factors for PFS-3, while ECOG PS(P = 0.007) and PFS-2(P < 0.001) were independent prognostic factors for OS-3.Conclusion Few patients with SCLC receive third-line chemotherapy. Our findings suggest that patients with an ECOG PS 0–1 and PFS-2 for >3 months will be benefit from third-line chemotherapy, which should be actively offered to them.
基金The study was reviewed and approved by the Rabin Medical Center Institutional Review Board(Approval No.0639-19-RMC).
文摘BACKGROUND In recent years survival of patients with metastatic colorectal cancer(mCRC),though still limited,has improved significantly;clearly,when the disease becomes refractory to standard regimens,additional treatment options are needed.Studies have shown that mitomycin C(MMC),an antitumor antibiotic,and capecitabine,a precursor of 5-fluorouracil,may act synergistically in combination.The efficacy of MMC/capecitabine has been demonstrated in the first-line setting,but only a few small studies have tested it in the advanced-line setting,with contradictory results.received a median of 2 MMC/capecitabine cycles(range 0.5-9.0).Thirty-four patients(28.6%)experienced grade≥3 toxicity,including 2(1.7%)with grade 4;there was no drug-related mortality.The objective response rate was 0.8%,and the disease control rate,24.4%.Median progression-free survival(PFS)was 2.1 mo(range 0.2-20.3),and median overall survival,4.8 mo(range 0.2-27.5).The 6-month overall survival rate was 44%;8.7%of patients remained progression-free.Factors associated with longer PFS were lower gamma-glutamyl transferase level(P=0.030)and primary tumor location in the left colon(P=0.017).Factors associated with longer overall survival were lower gamma-glutamyl transferase level(P=0.022),left-colon tumor location(P=0.044),low-to-moderate histological grade(P=0.012),Eastern Cooperative Oncology Group performance status 0-1(P=0.036),and normal bilirubin level(P=0.047).CONCLUSION MMC/capecitabine is an active,available,and relatively safe regimen for use beyond standard lines of therapy in mCRC.Several clinical and laboratory parameters can identify patients more likely to benefit.
文摘1文献来源Planchard D,Jänne PA,Cheng Y,et al.Osimertinib with or without chemotherapy in EGFR⁃mutated advanced NSCLC[J].N Engl J Med,2023,389(21):1935-1948.2证据水平1b。
文摘[目的]评价消癌平注射液联合一线化疗治疗晚期胃癌的疗效及安全性。[方法]检索发表于中国知网(CNKI)、万方数据库(WanFang)、维普数据库(VIP)、Pubmed以及Web of science共5个中英文数据库中有关消癌平注射液联合一线化疗方案治疗晚期胃癌的随机对照试验(RCT),检索时间范围设定为各数据库自建库以来至2023年10月27日,对符合纳入排除标准的研究进行偏倚风险评价及Meta分析。[结果]共纳入10项RCT,共包含814例晚期胃癌患者;在近期疗效方面消癌平注射液联合一线化疗方案能够有效提升客观缓解率(ORR)[RR:1.35,95%CI(1.15,1.58),P=0.0002]以及卡氏评分(KPS)[RR:1.62,95%CI(1.16,2.26),P=0.005];且3-4级不良反应事件(SAE)发生数量少于单纯化疗[RR:0.32,95%CI(0.06,0.90),P=0.04];在远期生存获益方面,消癌平注射液联合一线化疗方案在无进展生存期(PFS)[HR:0.32,95%CI(0.17,0.62),P=0.0007]以及总生存期(OS)[HR:0.33,95%CI(0.16,0.65),P=0.002]方面均优于单纯化疗;GRADE分级结果显示,ORR、KPS、PFS、OS为低等级质量证据,SAE为极低等级质量证据。[结论]消癌平注射液联合一线化疗具有良好的临床疗效及安全性,但纳入文献的方法学质量较低,尚需要更加全面的大样本、多中心、随机双盲对照实验进行验证。
