Randomized phase III trial of gemcitabine plus cisplatin compared with gemcitabine alone in advanced pancreatic cancer.

PURPOSE: To compare the effectiveness and tolerability of gemcitabine plus cisplatin with single-agent gemcitabine as first-line chemotherapy for locally advanced or metastatic pancreatic cancer. PATIENTS AND METHODS: Patients with advanced adenocarcinoma of the pancreas were randomly assigned to receive either gemcitabine 1,000 mg/m2 and cisplatin 50 mg/m2 given on days 1 and 15 of a 4-week cycle (GemCis arm) or gemcitabine alone at a dose of 1,000 mg/m2 on days 1, 8, and 15 of a 4-week regimen (Gem arm). The primary end point was overall survival; secondary end points were progression-free survival, response rate, safety, and quality of life. RESULTS: One hundred ninety-five patients were enrolled and showed baseline characteristics well balanced between treatment arms. Combination treatment in the GemCis arm was associated with a prolonged median progression-free survival (5.3 months v 3.1 months; hazard ratio [HR] = 0.75; P = .053). Also, median overall survival was superior for patients treated in the GemCis arm as compared with the Gem arm (7.5 v 6.0 months), an advantage which did not, however, reach statistical significance (HR = 0.80; P = .15). Tumor response rates were comparable between treatment arms (10.2% v 8.2%). The rate of stable disease was, however, greater in the combination arm (60.2% v 40.2%; P < .001). Grade 3 to 4 hematologic toxicity did not exceed 15% in both treatment arms. CONCLUSION: These results support the efficacy and safety of an every-2-weeks treatment with gemcitabine plus cisplatin. Median overall survival and progression-free survival were more favorable in the combination arm as compared with gemcitabine alone, although the difference did not attain statistical significance.

Low-molecular-weight heparin does not prevent acute post-ERCP pancreatitis.

BACKGROUND: Studies suggest that heparin has anti-inflammatory effects that could prevent acute post-ERCP pancreatitis. The aim of this investigator-initiated, prospective, randomized, double-blind, multicenter study was to determine whether low-molecular-weight heparin can prevent acute post-ERCP pancreatitis. METHODS: Patients at increased risk for acute post-ERCP pancreatitis based on assessment of known risk factors were randomized to receive low-molecular-weight heparin (Certoparin 3000 IU subcutaneously) or placebo (saline solution 0.3 mL subcutaneously) the day before ERCP. The drug was given 2 hours before and 22 hours after ERCP. Documentation and follow-up included patient history, risk factors for acute post-ERCP pancreatitis, procedure-related data, assessment of pain (visual analogue scale, need for pain medication), laboratory findings before and after ERCP (0, 4, and 24 hours), as well as post-ERCP complications. The two-sided Fisher exact test was used for statistical comparison, and a p value < or =0.05 was considered significant. RESULTS: A total of 458 patients were enrolled in the study. Data from 10 patients could not be evaluated, leaving 221 patients in the low-molecular-weight heparin group and 227 in the placebo group (total 448 patients; 135 men, 313 women; mean age 58 [15] years). Low-molecular-weight heparin and placebo groups were comparable with regard to risk factors for acute post-ERCP pancreatitis (gender distribution, age <65 years, history of pancreatitis, pancreas divisum, disorders of sphincter of Oddi) and procedure-related data (difficult cannulation, diagnostic or therapeutic ERCP, needle-knife papillotomy, endoscopic sphincterotomy, biliary or pancreatic procedure, pancreatic contrast injection, success and final diagnosis of ERCP). Acute post-ERCP pancreatitis occurred in 8.5% (38/448), with one death resulting from severe pancreatitis. Low-molecular-weight heparin offered no benefit compared with placebo based on the frequency of acute post-ERCP pancreatitis (low-molecular-weight heparin, 18/221 vs. placebo, 20/227; p=0.87) and the severity of acute post-ERCP pancreatitis (low-molecular-weight heparin, 14 mild, 3 moderate, one severe; placebo, 18 mild, two moderate, 0 severe). The 24-hour serum amylase values and 24-hour pain scores did not differ significantly between the low-molecular-weight heparin group and the placebo group. Bleeding complications occurred in two patients, both in the low-molecular-weight heparin group (one mild, one moderate). CONCLUSIONS: Prophylactic subcutaneous administration of low-molecular-weight heparin does not prevent acute post-ERCP pancreatitis.