Adjuvant chemotherapy with gemcitabine and long-term outcomes among patients with resected pancreatic cancer: Results from the CONKO-001 study
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Adjuvant chemotherapy with gemcitabine and long-term outcomes among patients with resected pancreatic cancer: Results from the CONKO-001 study. / Oettle, Helmut; Neuhaus, Peter; Hochhaus, Andreas; Hartmann, Jörg Thomas; Gellert, Klaus; Ridwelski, Karsten; Niedergethmann, Marco; Zülke, Carl; Fahlke, Jörg; Arning, Michael B; Sinn, Marianne; Hinke, Axel; Riess, Hanno.
In: JAMA-J AM MED ASSOC, Vol. 310, No. 14, 09.10.2013, p. 1473-81.Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review
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TY - JOUR
T1 - Adjuvant chemotherapy with gemcitabine and long-term outcomes among patients with resected pancreatic cancer: Results from the CONKO-001 study
AU - Oettle, Helmut
AU - Neuhaus, Peter
AU - Hochhaus, Andreas
AU - Hartmann, Jörg Thomas
AU - Gellert, Klaus
AU - Ridwelski, Karsten
AU - Niedergethmann, Marco
AU - Zülke, Carl
AU - Fahlke, Jörg
AU - Arning, Michael B
AU - Sinn, Marianne
AU - Hinke, Axel
AU - Riess, Hanno
PY - 2013/10/9
Y1 - 2013/10/9
N2 - 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 (Charité Onkologie 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.
AB - 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 (Charité Onkologie 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.
KW - Adult
KW - Aged
KW - Aged, 80 and over
KW - Antimetabolites, Antineoplastic/adverse effects
KW - Chemotherapy, Adjuvant
KW - Deoxycytidine/adverse effects
KW - Female
KW - Humans
KW - Male
KW - Middle Aged
KW - Neoplasm Recurrence, Local
KW - Pancreatic Neoplasms/drug therapy
KW - Survival Analysis
U2 - 10.1001/jama.2013.279201
DO - 10.1001/jama.2013.279201
M3 - SCORING: Journal article
C2 - 24104372
VL - 310
SP - 1473
EP - 1481
JO - JAMA-J AM MED ASSOC
JF - JAMA-J AM MED ASSOC
SN - 0098-7484
IS - 14
ER -