Efficacy of Prophylactic Low-Molecular Weight Heparin for Ambulatory Patients With Advanced Pancreatic Cancer: Outcomes From the CONKO-004 Trial.

PURPOSE: Advanced pancreatic cancer (APC), in addition to its high mortality, accounts for the highest rates of venous thromboembolic events (VTEs). Enoxaparin, a low-molecular weight heparin, is effective in prevention and treatment of VTEs. Some small studies have indicated that this benefit might extend to patients with cancer. PATIENTS AND METHODS: Patients with histologically proven APC were randomly assigned to ambulant first-line chemotherapy and prophylactic use of enoxaparin or chemotherapy alone to investigate the probable reduction in symptomatic VTEs and the impact on survival. RESULTS: A total of 312 patients were recruited as one of the protocol end points was reached. Within the first 3 months, the numbers of symptomatic VTEs were as follows: 15 of 152 patients in the observation group and two of 160 patients in the enoxaparin group (hazard ratio [HR], 0.12; 95% CI, 0.03 to 0.52; χ(2) P = .001). The numbers of major bleeding events were as follows: five of 152 patients in the observation arm and seven of 160 patients in the enoxaparin arm (HR, 1.4; 95% CI, 0.35 to 3.72; χ(2) P = 1.0). Overall cumulative incidence rates of symptomatic VTEs were 15.1% (observation) and 6.4% (enoxaparin; HR, 0.40; 95% CI, 0.19 to 0.83; P = .01). Progression-free (HR, 1.06; 95% CI, 0.84 to 1.32; P = .64) and overall survival (HR, 1.01; 95% CI, 0.87 to 1.38; P = .44) did not differ between groups. CONCLUSION: This study demonstrates the high efficacy and feasibility of primary pharmacologic prevention of symptomatic VTEs in outpatients with APC. Treatment efficacy was not affected by simultaneous treatment with enoxaparin in this trial setting.

First-line treatment of pancreatic cancer patients with the combination of 5-fluorouracil/folinic acid plus gemcitabine: a multicenter phase II trial by the CONKO-study group.

PURPOSE: This open-label, multi-center phase II study investigated the efficacy and safety of the combination of 5-fluorouracil (5-FU)/folinic acid (FA) plus gemcitabine (GFF) in patients with advanced pancreatic cancer. The study is based on our completed dose finding phase I trial. METHODS: A total of 90 patients (pts) were recruited between 02/2000 and 04/2002 to receive 5-FU 750 mg/m(2) (24 h, i.v.), FA 500 mg/m(2) (2 h, i.v.) and gemcitabine 1,000 mg/m(2) (30 min, i.v.) on days 1, 8, 15, and 22. Treatment was repeated on day 43 until disease progression. The primary objective was the 1-year survival rate. The trial was conducted in compliance with the Declaration of Helsinki. RESULTS: The 1-year survival rate was 25% [95% CI: 16-34], median overall survival was 6.8 months [95% CI: 5.13-8.45], 9 patients showed partial responses (PR) so that the overall response rate was 10.3%. Overall control rate (PR + stable disease for at least 6 months) was 56%. Median time to progression was 4.6 months [95% CI: 3.68-5.52]. In 402 GFF cycles, we observed adverse events grade 3 in up to 10% of patients and grade 4 below 5% of patients. CONCLUSIONS: The GFF combination appears to be effective and well tolerated. This intravenous regimen represents an intensified therapy with low frequency of toxicities and seems to be convenient for patients who are unable to get oral anti-neoplastic medication. After these encouraging results, the German CONKO-002 trial investigated the GFF regimen versus single-agent gemcitabine.

A prospective two-center study comparing wireless capsule endoscopy with intraoperative enteroscopy in patients with obscure GI bleeding.

BACKGROUND: Capsule endoscopy enables noninvasive diagnostic examination of the entire small intestine. However, sensitivity and specificity of capsule endoscopy have not been adequately defined. We, therefore, compared capsule endoscopy by using intraoperative enteroscopy as a criterion standard in patients with obscure GI bleeding. METHODS: Forty-seven consecutive patients with obscure GI bleeding (11 with ongoing overt bleeding, 24 with previous overt bleeding, and 12 with obscure-occult bleeding) from two German gastroenterologic centers were included. All patients who had a prior nondiagnostic evaluation, including upper endoscopy, colonoscopy with a retrograde examination of the distal ileum, and push enteroscopy, underwent capsule endoscopy followed by intraoperative enteroscopy. RESULTS: Capsule endoscopy identified lesions in 100% of the patients with ongoing overt bleeding, 67% of the patients with previous overt bleeding, and 67% of the patients with obscure-occult bleeding. Angiectasias were the most common source of bleeding (n = 22). Capsule endoscopy showed the source of bleeding in 74.4% of all patients. The method was more effective in patients with ongoing bleeding. Compared with intraoperative enteroscopy sensitivity, specificity, and positive and negative predictive values of capsule endoscopy were 95%, 75%, 95%, and 86%, respectively. CONCLUSIONS: Capsule endoscopy has high sensitivity and specificity to detect a bleeding source in patients with obscure GI bleeding. Thus, wireless capsule endoscopy can be recommended as part of the routine work-up in patients with obscure GI bleeding.