Article

Title/Citation

BACKGROUND AND OVERVIEW

Adjuvant chemotherapy with gemcitabine vs observation in patients undergoing
curative-intent resection of pancreatic cancer: a randomized controlled trial.
Oettle H(1), 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. JAMA. 2007 Jan 17;297(3):267-77.

Study
Objectives/pur
pose
Brief
background

Funding
Sources
Study design
and
methodology

Patient
selection &
enrollment

Outcome
measures/end
points

Summary of
study results,
focusing on
primary and
secondary
outcomes

*The purpose of this study was to test the hypothesis that adjuvant chemotherapy with
gemcitabine administered after complete resection of pancreatic cancer improves diseasefree survival by 6 months or more.
*Pancreatic cancer is one of the most common malignancies worldwide with an estimated
232,000 new cases.
*4th leading cause of death from cancer in the USA with 32,300 deaths in 2006
*Surgery is the ONLY curative treatment but 2/2 to aggressive nature, few patients present
with resectable disease and even with surgery prognosis is poor with a 5-year survival s/p
pancreatectomy of only 23.4%
*Surgery alone is inadequate and there is a need for adjuvant chemotherapy combined with
surgery to optimize outcomes
Grant from Lilly Deutschland, Germany
METHODS
*Open, multicenter, randomized controlled phase 3 trial with an active treatment group
(adjuvant gemcitabine) and a control group (observation only).
*Patients in the gemcitabine group received adjuvant chemotherapy with 6 cycles of
gemcitabine every 4 weeks
*Gemcitabine was started between 1042 days s/p surgery and each cycle consisted of 3
weekly infusions of 1000mg followed by a 1-week pause
*Study designed to reject the null hypothesis that adjuvant chemotherapy with gemcitabine
did not improve disease-free survival
*Conducted from July 1998 to December 2004 in the outpatient setting at 88 academic and
community based oncology centers in Germany and Austria.
*368 patients with gross complete (R0 or R1) resection of pancreatic cancer and no prior
radiation or chemotherapy were enrolled into 2 groups.
*Patients were required to have stage T1-4 N0-1 and M0 disease prior to surgery
*Primary endpoint disease free survival = time from randomization to the date of local
recurrence or death
*Secondary endpoing toxicity, quality of life (Spitzer index), and overall survival (death
from any cause)
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