PEFG (cisplatin, Epirubicin, 5-fluorouracil, Gemcitabine) Regimen As Second-line Therapy in Patients with Progressive or Recurrent Pancreatic Cancer After Gemcitabine-containing Chemotherapy

Objective: The therapeutic arsenal for salvage therapy in pancreatic cancer is limited. PEFG (cisplatin, epirubicin, 5-fluorouracil [FU], gemcitabine) regimen is an effective upfront treatment in advanced pancreatic cancer. The activity and safety of this combination regimen were assessed by means of an observational study in a population of patients with progressive or recurrent pancreatic adenocarcinoma after gemcitabine-containing chemotherapy.

Methods: Patients with age <76 years, Karnofsky performance status >50 were treated with either classic PEFG (until April 2004: cisplatin and epirubicin 40 mg/m day 1, gemcitabine 600 mg/m day 1 and 8, FU 200 mg/m/d continuous infusion day 1-28) or dose-intense PEFG (since May 2004: cisplatin and epirubicin 30 mg/m, gemcitabine 800 mg/m every 14 days; FU 200 mg/m/d continuous infusion day 1-28) until progressive disease or a maximum of 6 cycles of 28 days.

Results: Forty-six patients (37 metastatic) received 69 cycles of classic PEFG (18 patients) or 104 cycles of dose-intense PEFG (28 patients) as second-line therapy. Prior treatment consisted of single agent gemcitabine (N = 17), gemcitabine-based chemotherapy (N = 4), or PEFG regimen (N = 25). Median previous progression-free survival was 7.6 months. Dose intensity (mg/m/wk) with classic PEFG was cisplatin and epirubicin 8.5; gemcitabine 230; FU 1035 and with dose-intense PEFG was cisplatin and epirubicin 11.5 (+36%); gemcitabine 259 (+13%); FU 1046 (+1%). Main grade >2 toxicity consisted of neutropenia in 26 patients (56%), thrombocytopenia in 10 (22%), anemia in 11 (24%), fatigue and stomatitis in 4 (9%), vomiting, diarrhea and hand-foot syndrome in 2 (4%). Partial response was observed in 11 patients (24%) (5 classic PEFG 28% + 6 dose-intense PEFG 21%). Median and 1-year survival was 8.3 months (8.0 vs. 9.0 months) and 26% (17% vs. 32%). Median and 6-months progression-free survival was 5.0 months (4.5 vs. 5.0 months) and 34% (33% vs. 38%).

Conclusions: PEFG regimen in gemcitabine refractory pancreatic cancer had an acceptable toxicity profile and interesting activity, and may constitute a treatment option in this setting.