547 Improvements in survival and clinical benefit with the use of gemcitabine (GEM) as first-line therapy for advanced pancreatic cancer: A randomized trial

Abstract

Following phase II clinical observations that patients with pancreas cancer experienced improvement in disease-related symptoms with GEM, a quantitative definition of clinical benefit (CB) was developed as a primary efficacy measure (Andersen, 1994, Proc ASCO 13:461). CB has 3 components: pain (based on analgesic consumption and pain intensity), Karnofsky performance status, and lean body mass increase. Each parameter was measured at baseline and regularly during study. Clinical benefit was define as a sustained improvement (≥4 weeks) in at least one parameter without a worsening in any other. Following a lead-in period to characterize and stabilize pain, 126 chemonaive patients with confirmed advanced or metastatic adenocarcinoma of the pancreas (measurableor evaluable) were randomized to GEM 1000 mg/m2 over 30 min wkly × 7 followed by 1 wk of rest, and then wkly × 3 every 4 wks thereafter, or to 5FU 600 mg/m2 over 30 mins once wkly. Patients on both treatment arms were balanced in terms of gender, age and disease stage. CB response was the primary endpoint: 23.8% of the GEM pts were CB responders versus 4.8% of 5FU pts (P = 0.0022). The median survival (months) was 5.65 for GEM versus 4.41 for 5FU (P = 0.0025), with 24% of GEM pts and 6% of 5FU pts alive at 9 months. WHO ≥grade 3 neutropenia was seen in 23% of GEM pts and 5% of 5FU pts, and ≥ grade 3 non-hematological toxicity (N&V, diarrhea) was seen in 15% of GEM pts and 10% of 5FU pts. This randomized study confirms the previously reported positive effect of gemcitabine on clinical benefit, and shows a survival benefit for GEM as initial treatment of patients with pancreatic cancer. Following phase II clinical observations that patients with pancreas cancer experienced improvement in disease-related symptoms with GEM, a quantitative definition of clinical benefit (CB) was developed as a primary efficacy measure (Andersen, 1994, Proc ASCO 13:461). CB has 3 components: pain (based on analgesic consumption and pain intensity), Karnofsky performance status, and lean body mass increase. Each parameter was measured at baseline and regularly during study. Clinical benefit was define as a sustained improvement (≥4 weeks) in at least one parameter without a worsening in any other. Following a lead-in period to characterize and stabilize pain, 126 chemonaive patients with confirmed advanced or metastatic adenocarcinoma of the pancreas (measurableor evaluable) were randomized to GEM 1000 mg/m2 over 30 min wkly × 7 followed by 1 wk of rest, and then wkly × 3 every 4 wks thereafter, or to 5FU 600 mg/m2 over 30 mins once wkly. Patients on both treatment arms were balanced in terms of gender, age and disease stage. CB response was the primary endpoint: 23.8% of the GEM pts were CB responders versus 4.8% of 5FU pts (P = 0.0022). The median survival (months) was 5.65 for GEM versus 4.41 for 5FU (P = 0.0025), with 24% of GEM pts and 6% of 5FU pts alive at 9 months. WHO ≥grade 3 neutropenia was seen in 23% of GEM pts and 5% of 5FU pts, and ≥ grade 3 non-hematological toxicity (N&V, diarrhea) was seen in 15% of GEM pts and 10% of 5FU pts. This randomized study confirms the previously reported positive effect of gemcitabine on clinical benefit, and shows a survival benefit for GEM as initial treatment of patients with pancreatic cancer.