• Gastrointestinal Cancers Clinical Trials
• Adjuvant/Neoadjuvant Therapy

If their disease is caught early enough, patients with pancreatic cancer (PC) may undergo a resection of the diseased organ; this procedure, though intended to be curative, most often results in only a modest increase in overall survival (OS). As with other cancers, it is possible that adjuvant chemotherapy may improve long-term outcome, but there is no approved or accepted therapeutic in this setting. For patients with advanced PC, treatment with gemcitabine (GEM) is the standard of care, making it the logical choice for investigative use after resection of the pancreas.

To date, there has not been enough evidence to warrant the standardization of this approach. However, data presented by Ulf Neumann, MD, Charité Universitatsmedizin Berlin, Berlin, Germany, added to the position that adjuvant treatment with gemcitabine should be seriously considered (Abstract #LBA 4504. ASCO 2008).

This phase 3, randomized, multicenter investigation (CONKO-001) looked at the adjuvant use of gemcitabine versus observation in patients with complete PC resection (R0 or R1; n=368). Patients were first stratified by resection status, nodal tumor involvement, and tumor stage and then randomized to observation or treatment with GEM 1000 mg/m2 on Days 1, 8, and 15 every 4 weeks for a total of 6 months. The primary endpoint of the study was disease-free survival (DFS) with secondary endpoints that included OS and the parameters of toxicity.

“We already demonstrated safety data and efficacy for adjuvant treatment with gemcitabine in patients with resected pancreatic cancer 3 years ago,” (Abstract #4014. ASCO 2007; Oettle et al. JAMA 2007) said Dr. Neumann. This final analysis, performed in March, incorporated data up to December 1, 2007, with 303 events in DFS (86.6%) and 293 events for OS (82.8%).

Results showed a median DFS of 13.4 months for GEM versus 6.9 months for observation (p=0.001). The proportion of patients with DFS at 5 years was 16% for GEM versus 6.5% for the observation arm. “Additionally, an unplanned subpopulation analysis showed the beneficial effect of gemcitabine in R0, R1, node-positive, node-negative, T1–2, and T3–4 tumors… all significant.”

Perhaps what was most interesting was the significant improvement of OS in the final analysis, which in the preliminary report of this investigation had not reached significance. In this final analysis, median OS was 22.8 months for GEM as compared with 20.2 months for observation (p=0.005). This benefit was maintained out to 5 years, at which point a survival rate of 21% was recorded for the treatment arm versus 9% for observation.

• © 2008 MD Conference Express