gms | German Medical Science

Objective: Gemcitabine (G) is still standard first line therapy in patiens with advanced pancreatic cancer. No standard second line regimen is now available after disease progression while receiving gemcitabine. Our phase II study (ASCO 2002) showed activity of the OFF regimen in 23 patients (pts). To confirm these data we started this multicenter phase III study to determine the efficiency and toxicity of OFF vs. BSC.

Methods: Following CT/ MRT confirmed failure with G in 1st line therapy we randomized pts. to BSC with OFF (A) or BSC (B) alone. Stratification included duration of 1st line therapy, Karnofsky Performance Status (KPS) and tumor stage. OFF as outpatient regimen: FU 2g/m² (24h)/FA 200 mg/m² (30min) on d1, d8, d15, d22 in combination with Oxaliplatin 85mg/m² (2h) on day 8 and 22. No therapy was given on days 23 to 42. Eligibility criteria were KPS>60%, controlled pain, adequate hematological, renal and liver functions.

Results: 46 pts. were randomized between 12/02 and 12/03. Both arms were well balanced regarding age, tumor stage, sex and KPS. The OFF regimen was tolerated with moderate toxicities similar to our phase II study. Median first line therapy (G) was in Arm A 21 weeks and in Arm B 20 weeks. Median survival time after first line progression in Arm A was 21 [95%CI; 18,7; 23,3] weeks and in Arm B 10 [95%CI; 7,7; 12,3] weeks; p=0,0077. The whole overall survival time in Arm A was 40 [95%CI 30,4; 48,8] weeks and in Arm B 34,4 [95%CI; 21,6; 47,2] weeks; p=0,0312.

Conclusion: The OFF regimen as second line therapy after gemcitabine is feasible with acceptable toxicity in advanced pancreatic cancer. We showed in this small trial a significant difference between OFF+BSC and BSC alone regarding survival after progression of first line therapy and overall survival.