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Medline ® Abstracts for References 14-23

of '潜在可切除外分泌胰腺癌的治疗'

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Adjuvant chemotherapy with gemcitabine vs observation in patients undergoing curative-intent resection of pancreatic cancer: a randomized controlled trial.
AU
Oettle H, Post S, Neuhaus P, Gellert K, Langrehr J, Ridwelski K, Schramm H, Fahlke J, Zuelke C, Burkart C, Gutberlet K, Kettner E, Schmalenberg H, Weigang-Koehler K, Bechstein WO, Niedergethmann M, Schmidt-Wolf I, Roll L, Doerken B, Riess H
SO
JAMA. 2007;297(3):267.
 
CONTEXT: The role of adjuvant therapy in resectable pancreatic cancer is still uncertain, and no recommended standard exists.
OBJECTIVE: To test the hypothesis that adjuvant chemotherapy with gemcitabine administered after complete resection of pancreatic cancer improves disease-free survival by 6 months or more.
DESIGN, SETTING, AND PATIENTS: Open, multicenter, randomized controlled phase 3 trial with stratification for resection, tumor, and node status. Conducted from July 1998 to December 2004 in the outpatient setting at 88 academic and community-based oncology centers in Germany and Austria. A total of 368 patients with gross complete (R0 or R1) resection of pancreatic cancer and no prior radiation or chemotherapy were enrolled into 2 groups.
INTERVENTION: Patients received adjuvant chemotherapy with 6 cycles of gemcitabine on days 1, 8, and 15 every 4 weeks (n = 179), or observation ([control]n = 175).
MAIN OUTCOME MEASURES: Primary end point was disease-free survival, and secondary end points were overall survival, toxicity, and quality of life. Survival analysis was based on all eligible patients (intention-to-treat).
RESULTS: More than 80% of patients had R0 resection. The median number of chemotherapy cycles in the gemcitabine group was 6 (range, 0-6). Grade 3 or 4 toxicities rarely occurred with no difference in quality of life (by Spitzer index) between groups. During median follow-up of 53 months, 133 patients (74%) in the gemcitabine group and 161 patients (92%) in the control group developed recurrent disease. Median disease-free survival was 13.4 months in the gemcitabine group (95% confidence interval, 11.4-15.3) and 6.9 months in the control group (95% confidence interval, 6.1-7.8; P<.001, log-rank). Estimated disease-free survival at 3 and 5 years was 23.5% and 16.5% in the gemcitabine group, and 7.5% and 5.5% in the control group, respectively. Subgroup analyses showed that the effect of gemcitabine on disease-free survival was significant in patients with either R0 or R1 resection. There was no difference in overall survival between the gemcitabine group (median, 22.1 months; 95% confidence interval, 18.4-25.8; estimated survival, 34% at 3 years and 22.5% at 5 years) and the control group (median, 20.2 months; 95% confidence interval, 17-23.4; estimated survival, 20.5% at 3 years and 11.5% at 5 years; P = .06, log-rank).
CONCLUSIONS: Postoperative gemcitabine significantly delayed the development of recurrent disease after complete resection of pancreatic cancer compared with observation alone. These results support the use of gemcitabine as adjuvant chemotherapy in resectable carcinoma of the pancreas.
TRIAL REGISTRATION: isrctn.org Identifier: ISRCTN34802808.
AD
Department of Medical Oncology and Hematology, CharitéSchool of Medicine, Campus Virchow-Klinikum, Berlin, Germany. helmut.oettle@charite.de
PMID
15
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Adjuvant combination chemotherapy (AMF) following radical resection of carcinoma of the pancreas and papilla of Vater--results of a controlled, prospective, randomised multicentre study.
AU
Bakkevold KE, ArnesjøB, Dahl O, Kambestad B
SO
Eur J Cancer. 1993;29A(5):698.
 
Between 1984 and 1987, 61 radically resected patients with carcinoma of the pancreas (n = 47) or the papilla of Vater (n = 14) were randomised either into postoperative adjuvant combination chemotherapy (AMF); 5-fluorouracil 500 mg/m2, doxorubicin 40 mg/m2, mitomycin C 6 mg/m2 (n = 30) once every 3 weeks for six cycles, or into a control group (no adjuvant chemotherapy) (n = 31). The median survival in the treatment group was 23 months compared with 11 months (P = 0.02, median test) in the control group, dependent on a survival benefit in the treatment group during the initial 2 years (P = 0.04 generalised Wilcoxon). The long-term prognosis was the same with an identical survival after 2 years (P = 0.10, power = 0.83). The observed 1, 2, 3 and 5-year survivals in the treatment group were 70, 43, 27 and 4% compared with 45, 32, 30 and 8 in the control group. 1 patient succumbed to sepsis probably attributable to chemotherapy. Cardiotoxicity and nephrotoxicity were recorded in 2 patients. These results suggest that adjuvant chemotherapy does postpone the incidence of recurrence in the first 2 years following radical surgery but increased cure rate was not observed.
AD
Department of Surgery Haugesund Hospital, Norway.
PMID
16
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Adjuvant chemoradiotherapy and chemotherapy in resectable pancreatic cancer: a randomised controlled trial.
AU
Neoptolemos JP, Dunn JA, Stocken DD, Almond J, Link K, Beger H, Bassi C, Falconi M, Pederzoli P, Dervenis C, Fernandez-Cruz L, Lacaine F, Pap A, Spooner D, Kerr DJ, Friess H, Büchler MW, European Study Group for Pancreatic Cancer
SO
Lancet. 2001;358(9293):1576.
 
BACKGROUND: The role of adjuvant treatment in pancreatic cancer remains uncertain. The European Study Group for Pancreatic Cancer (ESPAC) assessed the roles of chemoradiotherapy and chemotherapy in a randomised study.
METHODS: After resection, patients were randomly assigned to adjuvant chemoradiotherapy (20 Gy in ten daily fractions over 2 weeks with 500 mg/m(2) fluorouracil intravenously on days 1-3, repeated after 2 weeks) or chemotherapy (intravenous fluorouracil 425 mg/m(2) and folinic acid 20 mg/m(2) daily for 5 days, monthly for 6 months). Clinicians could randomise patients into a two-by-two factorial design (observation, chemoradiotherapy alone, chemotherapy alone, or both) or into one of the main treatment comparisons (chemoradiotherapy versus no chemoradiotherapy or chemotherapy versus no chemotherapy). The primary endpoint was death, and all analyses were by intention to treat. Findings 541 eligible patients with pancreatic ductal adenocarcinoma were randomised: 285 in the two-by-two factorial design (70 chemoradiotherapy, 74 chemotherapy, 72 both, 69 observation); afurther 68 patients were randomly assigned chemoradiotherapy or no chemoradiotherapy and 188 chemotherapy or no chemotherapy. Median follow-up of the 227 (42%) patients still alive was 10 months (range 0-62). Overall results showed no benefit for adjuvant chemoradiotherapy (median survival 15.5 months in 175 patients with chemoradiotherapy vs 16.1 months in 178 patients without; hazard ratio 1.18 [95% CI 0.90-1.55], p=0.24). There was evidence of a survival benefit for adjuvant chemotherapy (median survival 19.7 months in 238 patients with chemotherapy vs 14.0 months in 235 patients without; hazard ratio 0.66 [0.52-0.83], p=0.0005). Interpretation This study showed no survival benefit for adjuvant chemoradiotherapy but revealed a potential benefit for adjuvant chemotherapy, justifying further randomised controlled trials of adjuvant chemotherapy in pancreatic cancer.
AD
Department of Surgery, Liverpool University, Liverpool, UK. j.p.neoptplemos@liverpool.ac.uk
PMID
17
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A randomized trial of chemoradiotherapy and chemotherapy after resection of pancreatic cancer.
AU
Neoptolemos JP, Stocken DD, Friess H, Bassi C, Dunn JA, Hickey H, Beger H, Fernandez-Cruz L, Dervenis C, Lacaine F, Falconi M, Pederzoli P, Pap A, Spooner D, Kerr DJ, Büchler MW, European Study Group for Pancreatic Cancer
SO
N Engl J Med. 2004;350(12):1200.
 
BACKGROUND: The effect of adjuvant treatment on survival in pancreatic cancer is unclear. We report the final results of the European Study Group for Pancreatic Cancer 1 Trial and update the interim results.
METHODS: In a multicenter trial using a two-by-two factorial design, we randomly assigned 73 patients with resected pancreatic ductal adenocarcinoma to treatment with chemoradiotherapy alone (20 Gy over a two-week period plus fluorouracil), 75 patients to chemotherapy alone (fluorouracil), 72 patients to both chemoradiotherapy and chemotherapy, and 69 patients to observation.
RESULTS: The analysis was based on 237 deaths among the 289 patients (82 percent) and a median follow-up of 47 months (interquartile range, 33 to 62). The estimated five-year survival rate was 10 percent among patients assigned to receive chemoradiotherapy and 20 percent among patients who did not receive chemoradiotherapy (P=0.05). The five-year survival rate was 21 percent among patients who receivedchemotherapy and 8 percent among patients who did not receive chemotherapy (P=0.009). The benefit of chemotherapy persisted after adjustment for major prognostic factors.
CONCLUSIONS: Adjuvant chemotherapy has a significant survival benefit in patients with resected pancreatic cancer, whereas adjuvant chemoradiotherapy has a deleterious effect on survival.
AD
Department of Surgery, Liverpool University, Liverpool, United Kingdom.
PMID
18
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Influence of resection margins and treatment on survival in patients with pancreatic cancer: meta-analysis of randomized controlled trials.
AU
Butturini G, Stocken DD, Wente MN, Jeekel H, Klinkenbijl JH, Bakkevold KE, Takada T, Amano H, Dervenis C, Bassi C, Büchler MW, Neoptolemos JP, Pancreatic Cancer Meta-Analysis Group
SO
Arch Surg. 2008;143(1):75.
 
OBJECTIVE: To assess the influence of resection margins and adjuvant chemoradiotherapy or chemotherapy on survival for patients with pancreatic cancer by meta-analysis of individual data from randomized controlled trials.
DATA SOURCES: Structured MEDLINE search for published studies.
STUDY SELECTION: A meta-analysis of published randomized controlled trials and individual data.
DATA EXTRACTION: Individual data were obtained from 4 recently published trials (875 patients: 278 [32%]with R1 and 591 [68%]with R0 resections).
DATA SYNTHESIS: Kaplan-Meier estimates of survival were compared using log-rank analyses. Pooled hazard ratios of the effects of chemoradiotherapy and chemotherapy treatments on the risk of death were calculated separately and across groups according to resection margins status. Six hundred ninety-eight patients (80%) had died, with a median follow-up of 44 months in the surviving patients. Resection margin involvement was not a significant factor for survival (hazard ratio [HR], 1.10; 95% confidence interval [CI], 0.94-1.29; log-rank chi(2) = 1.4; P = .24). The 2- and 5-year survival rates, respectively, were 33% and 16% for R0 patients and 29% and 15% for R1 patients. Chemoradiotherapy in R1 patients resulted in a 28% reduction in the risk of death (HR, 0.72; 95% CI, 0.47-1.10) compared with a 19% increased risk in R0 patients (HR, 1.19; 95% CI, 0.95-1.49). Chemotherapy in R1 patients had a 4% increased risk of death (HR, 1.04; 95% CI, 0.78-1.40) compared with a 35% reduction in risk in the R0 subgroup (HR, 0.65; 95% CI, 0.53-0.80).
CONCLUSION: Adjuvant chemotherapy but not chemoradiotherapy should be the standard of care for patients with either R0 or R1 resections for pancreatic cancer.
AD
Division of Surgery and Oncology, School of Cancer Studies, Royal Liverpool University Hospital, 5th Floor, UCD Bldg, Daulby St, Liverpool L69 3GA, England. j.p.neoptolemos@liverpool.ac.uk
PMID
19
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Adjuvant 5-fluorouracil and folinic acid vs observation for pancreatic cancer: composite data from the ESPAC-1 and -3(v1) trials.
AU
Neoptolemos JP, Stocken DD, Tudur Smith C, Bassi C, Ghaneh P, Owen E, Moore M, Padbury R, Doi R, Smith D, Büchler MW
SO
Br J Cancer. 2009;100(2):246. Epub 2009 Jan 6.
 
The ESPAC-1, ESPAC-1 plus, and early ESPAC-3(v1) results (458 randomized patients; 364 deaths) were used to estimate the effectiveness of adjuvant 5FU/FA vs resection alone for pancreatic cancer using meta-analysis. The pooled hazard ratio of 0.70 (95% CI=0.55-0.88) P=0.003, and the median survival of 23.2 (95% CI=20.1-26.5) months with 5FU/FA vs 16.8 (95% CI=14.3-19.2) months with resection alone supports the use of adjuvant 5FU/FA in pancreatic cancer.
AD
CR-UK Liverpool Cancer Trials Unit, University of Liverpool Cancer Research Centre, Liverpool, UK. j.p.neoptolemos@liverpool.ac.uk
PMID
20
TI
Adjuvant chemotherapy with gemcitabine and long-term outcomes among patients with resected pancreatic cancer: the CONKO-001 randomized trial.
AU
Oettle H, Neuhaus P, Hochhaus A, Hartmann JT, Gellert K, Ridwelski K, Niedergethmann M, Zülke C, Fahlke J, Arning MB, Sinn M, Hinke A, Riess H
SO
JAMA. 2013;310(14):1473.
 
IMPORTANCE: The prognosis for patients with pancreatic cancer is poor, even after resection with curative intent. Gemcitabine-based chemotherapy is standard treatment for advanced pancreatic cancer, but its effect on survival in the adjuvant setting has not been demonstrated.
OBJECTIVE: To analyze whether previously reported improvement in disease-free survival with adjuvant gemcitabine therapy translates into improved overall survival.
DESIGN, SETTING, AND PATIENTS: CONKO-001 (CharitéOnkologie 001), a multicenter, open-label, phase 3 randomized trial to evaluate the efficacy and toxicity of gemcitabine in patients with pancreatic cancer after complete tumor resection. Patients with macroscopically completely removed pancreatic cancer entered the study between July 1998 and December 2004 in 88 hospitals in Germany and Austria. Follow-up ended in September 2012.
INTERVENTIONS: After stratification for tumor stage, nodal status, and resection status, patients were randomly assigned to either adjuvant gemcitabine treatment (1g/m2 d 1, 8, 15, q 4 weeks) for 6 months or to observation alone.
MAIN OUTCOMES AND MEASURES: The primary end point was disease-free survival. Secondary end points included treatment safety and overall survival, with overall survival defined as the time from date of randomization to death. Patients lost to follow-up were censored on the date of their last follow-up.
RESULTS: A total of 368 patients were randomized, and 354 were eligible for intention-to-treat-analysis. By September 2012, 308 patients (87.0% [95% CI, 83.1%-90.1%]) had relapsed and 316 patients (89.3% [95% CI, 85.6%-92.1%]) had died. The median follow-up time was 136 months. The median disease-free survival was 13.4 (95% CI, 11.6-15.3) months in the treatment group compared with 6.7 (95% CI, 6.0-7.5) months in the observation group (hazard ratio, 0.55 [95% CI, 0.44-0.69]; P < .001). Patients randomized to adjuvant gemcitabine treatment had prolonged overall survival compared with those randomized to observation alone (hazard ratio, 0.76 [95% CI, 0.61-0.95]; P = .01), with 5-year overall survival of 20.7% (95% CI, 14.7%-26.6%) vs 10.4% (95% CI, 5.9%-15.0%), respectively, and 10-year overall survival of 12.2% (95% CI, 7.3%-17.2%) vs 7.7% (95% CI, 3.6%-11.8%).
CONCLUSIONS AND RELEVANCE: Among patients with macroscopic complete removal of pancreatic cancer, the use of adjuvant gemcitabine for 6 months compared with observation alone resulted in increased overall survival as well as disease-free survival. These findings provide strong support for the use of gemcitabine in this setting.
TRIAL REGISTRATION: isrctn.org Identifier: ISRCTN34802808.
AD
Medizinische Klinik mit Schwerpunkt Hämatologie, Onkologie und Tumorimmunologie, Charité-Universitätsmedizin Berlin, Berlin, Germany. helmut.oettle@charite.de
PMID
21
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Adjuvant treatments for resected pancreatic adenocarcinoma: a systematic review and network meta-analysis.
AU
Liao WC, Chien KL, Lin YL, Wu MS, Lin JT, Wang HP, Tu YK
SO
Lancet Oncol. 2013;14(11):1095. Epub 2013 Sep 12.
 
BACKGROUND: Major adjuvant treatments for pancreatic adenocarcinoma include fluorouracil, gemcitabine, chemoradiation, and chemoradiation plus fluorouracil or gemcitabine. Since the optimum regimen remains inconclusive, we aimed to compare these treatments in terms of overall survival after tumour resection and in terms of grade 3-4 toxic effects with a systematic review and random-effects Bayesian network meta-analysis.
METHODS: We searched PubMed, trial registries, and related reviews and abstracts for randomised controlled trials comparing the above five treatments with each other or observation alone before April 30, 2013. We estimated relative hazard ratios (HRs) for death and relative odds ratios (ORs) for toxic effects among different therapies by combining HRs for death and survival durations and ORs for toxic effects of included trials. We assessed the effects of prognostic factors on survival benefits of adjuvant therapies with meta-regression.
FINDINGS: Ten eligible articles reporting nine trials were included. Compared with observation, the HRs for death were 0·62 (95% credible interval 0·42-0·88) for fluorouracil, 0·68 (0·44-1·07) for gemcitabine, 0·91 (0·55-1·46) for chemoradiation, 0·54 (0·15-1·80) for chemoradiation plus fluorouracil, and 0·44 (0·10-1·81) for chemoradiation plus gemcitabine. The proportion of patients with positive lymph nodes was inversely associated with the survival benefit of adjuvant treatments. After adjustment for this factor, fluorouracil (HR 0·65, 0·49-0·84) and gemcitabine (0·59, 0·41-0·83) improved survival compared with observation, whereas chemoradiation resulted in worse survival than fluorouracil (1·69, 1·12-2·54) or gemcitabine (1·86, 1·04-3·23). Chemoradiation plus gemcitabine was ranked the most toxic, with significantly higher haematological toxic effects than second-ranked chemoradiation plus fluorouracil (OR 13·33, 1·01-169·36).
INTERPRETATION: Chemotherapy with fluorouracil or gemcitabine is the optimum adjuvant treatment for pancreatic adenocarcinoma and reduces mortality after surgery by about a third. Chemoradiation plus chemotherapy is less effective in prolonging survival and is more toxic than chemotherapy.
FUNDING: None.
AD
Department of Internal Medicine, National Taiwan University Hospital, National Taiwan University College of Medicine, Taipei, Taiwan; Institute of Epidemiology and Preventive Medicine, College of Public Health, National Taiwan University, Taipei, Taiwan.
PMID
22
TI
A randomised phase III trial comparing gemcitabine with surgery-only in patients with resected pancreatic cancer: Japanese Study Group of Adjuvant Therapy for Pancreatic Cancer.
AU
Ueno H, Kosuge T, Matsuyama Y, Yamamoto J, Nakao A, Egawa S, Doi R, Monden M, Hatori T, Tanaka M, Shimada M, Kanemitsu K
SO
Br J Cancer. 2009;101(6):908. Epub 2009 Aug 18.
 
BACKGROUND: This multicentre randomised phase III trial was designed to determine whether adjuvant chemotherapy with gemcitabine improves the outcomes of patients with resected pancreatic cancer.
METHODS: Eligibility criteria included macroscopically curative resection of invasive ductal carcinoma of the pancreas and no earlier radiation or chemotherapy. Patients were randomly assigned at a 1 : 1 ratio to either the gemcitabine group or the surgery-only group. Patients assigned to the gemcitabine group received gemcitabine at a dose of 1000 mg m(-2) over 30 min on days 1, 8 and 15, every 4 weeks for 3 cycles.
RESULTS: Between April 2002 and March 2005, 119 patients were enrolled in this study. Among them, 118 were eligible and analysable (58 in the gemcitabine group and 60 in the surgery-only group). Both groups were well balanced in terms of baseline characteristics. Although heamatological toxicity was frequently observed in the gemcitabine group, most toxicities were transient, and grade 3 or 4 non-heamatological toxicity was rare. Patients in the gemcitabine group showed significantly longer disease-free survival (DFS) than those in the surgery-only group (median DFS, 11.4 versus 5.0 months; hazard ratio=0.60 (95% confidence interval (CI): 0.40-0.89); P=0.01), although overall survival did not differ significantly between the gemcitabine and surgery-only groups (median overall survival, 22.3 versus 18.4 months; hazard ratio=0.77 (95% CI: 0.51-1.14); P=0.19).
CONCLUSION: The current results suggest that adjuvant gemcitabine contributes to prolonged DFS in patients undergoing macroscopically curative resection of pancreatic cancer.
AD
Hepatobiliary and Pancreatic Oncology Division, National Cancer Center Hospital, Tokyo, Japan. hiueno@ncc.go.jp
PMID
23
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Gemcitabine Adjuvant Therapy for Resected Pancreatic Cancer: A Meta-analysis.
AU
Yu Z, Zhong W, Tan ZM, Wang LY, Yuan YH
SO
Am J Clin Oncol. 2015;38(3):322.
 
Gemcitabine (GEM) is an approved treatment for unresectable pancreatic cancer; however, its role in treating resected pancreatic cancer is less clear. The aim of this study was to investigate the evidence of the role of adjuvant GEM therapy on survival in resected pancreatic cancer. Four phase III randomized trials of adjuvant GEM in patients with resected pancreatic cancer were identified and the hazard ratio (HR) for overall survival were used in this meta-analysis; 2 studies compared GEM treatment with best supportive care and 2 studies with 5-fluorouracil/folinic acid therapy. The pooled data (n=2017 patients) indicated that the overall survival data were homogenous among the studies (Q=4.371; I=31.37%; P=0. 224). The combined HR significantly favors GEM over the other treatments. The overall HR was 0.88 (range, 0. 720 to 0.940; P=0.014). The results indicate that GEM prolongs overall survival compared with other treatments after the resection of pancreatic cancer.
AD
Departments of *Gastroenterology and Hepatology†Network Center, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, China.
PMID