A phase II, open-label, multicenter study to evaluate the antitumor efficacy of CO-1.01 as second-line therapy for gemcitabine-refractory patients with stage IV pancreatic adenocarcinoma and negative tumor hENT1 expression.

BACKGROUND: Nucleotide transporters such as human equilibrative nucleoside transporter-1 (hENT1) play a major role in transporting gemcitabine into cells. CO-1.01 (gemcitabine-5'-elaidate) is a novel cytotoxic agent consisting of a fatty acid derivative of gemcitabine, which is transported intracellularly independent of hENT1. CO-1.01 was postulated to have efficacy as a second-line treatment in gemcitabine-refractory pancreatic adenocarcinoma in patients with negative tumor hENT1 expression. METHODS: Eligibility criteria included patients with either a newly procured or archival biopsy tumor confirming the absence of hENT1 and either gemcitabine-refractory metastatic pancreas adenocarcinoma or with progression of disease following resection during or within 3 months of adjuvant gemcitabine therapy. Patients were treated with intravenous infusion of CO-1.01 dosed at 1250 mg/m(2) on Days 1, 8, and 15 of a 4-week cycle. The primary end point was disease control rate (DCR). RESULTS: Nineteen patients were enrolled of which 18 patients were evaluable for efficacy assessment. Thirteen patients (68%) had liver metastases, 6 (32%) had lymph node metastases, and 10 (53%) had lung metastases. Two of 18 patients (11%) achieved disease control. The median survival time was 4.3 (95% CI 2.1-8.1) months. All patients experienced at least one treatment-related adverse event with the majority of events being mild or moderate. CONCLUSION: This study did not meet its primary endpoint and no efficacy signal was identified for CO-1.01 in treating progressive metastatic pancreas adenocarcinoma.

[Clinical and functional results after Laparoscopic fundoplication. Prospective evaluation]. / Resultados clínicos y funcionales después de funduplicatura laparoscópica. Evaluación prospectiva.

OBJECTIVE: To prospectively assess the medium- and long-term clinical and functional results in consecutive patients undergoing laparoscopic procedures for gastroesophageal reflux. PATIENTS AND METHOD: The series included the interventions performed or assisted by the first author in 325 patients referred for surgical evaluation between December 1992 and June 2000. Forty patients were excluded from the study because they did not fulfil the inclusion criteria for laparoscopic surgery. A further 20 patients who underwent laparoscopic surgery were excluded because they required conversion to open surgery. Thus, 265 patients were included in the study. One hundred ninety-six total fundoplications (Nissen-Rossetti) and 69 partial fundoplications(42 posterior-Toupet and 27 anterior-Dor) were performed. The surgical technique employed was a slight modification of that described by Dallemagne et al with five-trocars. Preoperative evaluation was established by clinical features, endoscopy with biopsy, barium contrast radiography, esophageal manometry and esophageal pH monitoring. RESULTS: The mean follow-up was 47.1 3.3 months (range: 4-92 months). Heartburn, regurgitation, and dysphagia were relieved in 92.5%, 97.7%, and 88.1% of patients respectively. Complete relief of symptoms was achieved in all patients who presented preoperative respiratory symptoms as a complication of gastroesophageal reflux. Esophagitis healed in 98.2% of patients with preoperative esophagitis. Correction of lower esophageal sphincter pressure and lower esophageal sphincter length were statistically significant compared with preoperative status (p = 0.006 and p = 0.003, respectively). Pre- and postoperative differences in the percentage of patients with a pH < 4 in 24-hour ambulatory esophageal pH monitoring were also significant (p = 0.005), confirming correction of acid reflux. Morbidity appeared in 6.7% of patients and there was no mortality. Conversion to open procedures was required in 7.5%. The mean operative time was 115 6.3 minutes. CONCLUSIONS: These preliminary results suggest that when performed by experienced surgeons laparoscopic fundoplication provides an excellent alternative in selected patients with gastroesophageal reflux. Both medium- and long-term clinical and functional results, as well as morbidity, were satisfactory and were similar to those of open fundoplication.