Rationale and design of PROSPECT-CONKO 004: a prospective, randomized trial of simultaneous pancreatic cancer treatment with enoxaparin and chemotherapy).

BACKGROUND: Advanced pancreatic cancer, in addition to its high mortality, is characterized by one of the highest rates of venous thromboembolic events (VTE) as compared to other types of cancer. Enoxaparin, a low molecular weight heparin (LMWH), has proven to be effective for the prevention and treatment of VTE in surgical and general medical patients. Results of some small studies suggest that this benefit might extend to patients with cancer, however, enoxaparin is not currently indicated for this use. This phase IIb study was designed to analyze the efficacy of enoxaparin in patients with locally advanced or metastatic pancreatic cancer undergoing systemic chemotherapy. METHODS: The aim of this prospective multicenter trial is to compare concomitant treatment with enoxaparin to no anticoagulation in 540 patients. Primary endpoint is the incidence of clinically relevant VTE (symptomatic deep venous thrombosis (DVT) of the leg and/or pelvic and/or pulmonary embolism (PE)) within the first 3 months. Secondary endpoints include the incidence of symptomatic and asymptomatic VTE after 6, 9 and 12 months as well as remission at 3, 6, 9 and 12 months, overall survival and bleeding. TRIAL REGISTRATION: isrctn.org identifier CCT-NAPN-16752, controlled-trials.com identifier: ISRCTN02140505. RESULTS: An interim analysis for safety performed after inclusion of 152 patients revealed no increased risk of bleeding (5 pts vs. 6 pts, Chi2: 0.763). CONCLUSION: PROSPECT is a pivotal study in elucidating the role of low molecular weight heparins in advanced pancreatic cancer. Its results will lead to a new understanding of the role of heparins in the prevention of venous thromboembolism and of their effect on survival, remission rates and toxicity of chemotherapeutic regimens.

Pantoprazole on-demand effectively treats symptoms in patients with gastro-oesophageal reflux disease.

OBJECTIVE: The efficacy of pantoprazole as on-demand therapy for the long-term management of patients with mild gastro-oesophageal reflux disease (GORD) has been demonstrated in clinical studies. In this study, the efficacy of pantoprazole 20mg and esomeprazole 20mg as on-demand therapy for relief of symptoms of mild GORD was compared. METHODS: Patients with reflux oesophagitis grade A or B (Los Angeles classification) or endoscopy-negative reflux disease (enGORD) were treated with pantoprazole 20mg once daily for 28 days during the acute phase (AP, n = 236). Patients without heartburn during the final 3 days of the AP entered the long-term phase (LTP, n = 199) and were randomised to either pantoprazole 20mg or esomeprazole 20mg as on-demand treatment for 6 months. Antacids were provided as rescue medication during this phase. The mean intensities of the symptoms of heartburn, acid eructation and pain on swallowing, both separately and as a combined symptom score, together with the mean duration of these symptoms during on-demand treatment, were compared between the two treatment groups. The number of tablets taken was also compared. RESULTS: After 4 weeks of treatment with pantoprazole, 87.3% of patients had relief from heartburn, 74.1% from epigastric pain and 80.8% from acid eructation, according to the investigator assessment. A total of 236 patients were eligible for the on-demand phase. Based on patient diary data, on-demand treatment with pantoprazole resulted in significantly lower mean intensity of heartburn compared with that in the esomeprazole group (1.12 for pantoprazole and 1.32 for esomeprazole, respectively [p = 0.012], in the intention-to-treat [ITT] population). The mean symptom intensities of acid eructation and pain on swallowing, together with the duration of these symptoms, were comparable in the two treatment groups. The combined symptom score of the three symptoms heartburn, acid eructation and pain on swallowing was numerically lower in the pantoprazole group compared with the esomeprazole group (1.72 vs 1.99, respectively, in the ITT population). Tablet intake was comparable in both groups. Relief of symptoms in Helicobacter pylori-positive and -negative patients was also similar in both treatment groups. Both treatments were well tolerated with a good safety profile. CONCLUSION: On-demand therapy with either pantoprazole 20mg or esomeprazole 20mg is a comparably effective treatment strategy for the long-term treatment of non-erosive and mild GORD. However, the mean intensity of heartburn was significantly lower with pantoprazole treatment.

Pilot study of on-demand therapy with pantoprazole 20mg for long-term treatment in patients with mild gastro-oesophageal reflux disease.

BACKGROUND: Few clinical studies have demonstrated the efficacy of proton pump inhibitors (PPIs) as on-demand therapy for the long-term management of patients with mild gastro-oesophageal reflux disease (GORD). On-demand therapy with pantoprazole 20mg may offer an effective strategy for the management of mild GORD. METHODS: Patients with mild GORD grade 0 or 1 and heartburn of at least moderate intensity at the start of the study were treated with pantoprazole 20mg once daily for 28 days (n = 254). Patients with no heartburn during the final 3 days of the acute treatment phase entered the long-term treatment phase and took pantoprazole 20mg on demand for 6 months. Antacids were provided as rescue medication during this phase. The primary endpoint was the percentage of patients unwilling to continue the study because of insufficient control of symptoms. In addition, the intensities and the relapse rates for heartburn, acid eructation and epigastric pain were determined. RESULTS: At the end of the acute treatment phase, 234 of 254 patients (92.1%) were free from heartburn and entered the long-term treatment phase (intention-to-treat [ITT]). The time until study discontinuation because of inadequate control of heartburn during the on-demand treatment phase ranged from 9 to 147 days. In the ITT population, only 2.8% of patients were unwilling to continue the study because of insufficient heartburn control. Relapse rates were 4.3% for heartburn, 2.3% for acid eructation and 1.0% for epigastric pain. After 6 months of on-demand treatment, 82% of patients stated that improvements in their symptoms were maintained. For symptom control during the on-demand phase, patients took one tablet of pantoprazole 20mg every 2.3 days. Additionally, patients took one magaldrate tablet every 2.4 days. CONCLUSION: Results of this pilot study show that on-demand therapy with pantoprazole 20mg appears to be an effective treatment strategy for the long-term treatment of mild GORD. Treatment acceptance by patients was high.

Long-term management of gastroesophageal reflux disease with pantoprazole.

Gastroesophageal reflux disease (GERD) is a chronic, relapsing disease that can progress to major complications. Affected patients have poorer health-related quality of life than the general population. As GERD requires continued therapy to prevent relapse and complications, most patients with erosive esophagitis require long-term acid suppressive treatment. Thus GERD results in a significant cost burden and poor health-related quality of life. The effective treatment of GERD provides symptom resolution and high rates of remission in erosive esophagitis, lowers the incidence of GERD complications, improves health-related quality of life, and reduces the cost of this disease. Proton pump inhibitors are accepted as the most effective initial and maintenance treatment for GERD. Oral pantoprazole is a safe, well tolerated and effective initial and maintenance treatment for patients with nonerosive GERD or erosive esophagitis. Oral pantoprazole has greater efficacy than histamine H(2)-receptor antagonists and generally similar efficacy to other proton pump inhibitors for the initial and maintenance treatment of GERD. In addition, oral pantoprazole has been shown to improve the quality of life of patients with GERD and is associated with high levels of patient satisfaction with therapy. GERD appears to be more common and more severe in the elderly, and pantoprazole has shown to be an effective treatment for this at-risk population.