Keli Turner

New, effective therapies are needed for pancreatic ductal adenocarcinoma. Ipilimumab can mediate an immunologic tumor regression in other histologies. This phase II trial evaluated the efficacy of Ipilimumab for advanced pancreatic cancer. Subjects were adults with locally advanced or metastatic pancreas adenocarcinoma with measurable disease, good performance status, and minimal comorbidities. Ipilimumab was administered intravenously (3.0 mg/kg every 3 wk; 4 doses/course) for a maximum of 2 courses. Response rate by response evaluation criteria in solid tumors criteria and toxicity were measured. Twenty-seven subjects were enrolled (metastatic disease: 20 and locally advanced: 7) with median age of 55 years (27 to 68 y) and good performance status (26 with Eastern Cooperative Oncology Group performance status =0 to 1). Three subjects experienced ≥ grade 3 immune-mediated adverse events (colitis:1, encephalitis:1, hypohysitis:1). There were no responders by response evaluation criteria in solid tumors criteria but a subject experienced a delayed response after initial progressive disease. In this subject, new metastases after 2 doses of Ipilimumab established progressive disease. But continued administration of the agent per protocol resulted in significant delayed regression of the primary lesion and 20 hepatic metastases. This was reflected in tumor markers normalization, and clinically significant improvement of performance status. Single agent Ipilimumab at 3.0 mg/kg/dose is ineffective for the treatment of advanced pancreas cancer. However, a significant delayed response in one subject of this trial suggests that immunotherapeutic approaches to pancreas cancer deserve further exploration.

Diffuse malignant peritoneal mesothelioma (DMPM) is a rare and ultimately fatal cancer that was first recognized and described a century ago. It is a diffuse primary malignant condition arising from the mesothelial lining of the peritoneum, and its natural history is hallmarked by a propensity to progress almost exclusively within the abdominal cavity throughout the entire course of disease. Patients afflicted with DMPM most commonly present with nonspecific abdominal symptoms that lead to diagnosis when the condition is relatively advanced. Historically, median overall survival for patients with DMPM without treatment is very short, averaging 6 months. Systemic chemotherapy using pemetrexed and cisplatin has an overall response rate of approximately 25% and a median overall survival of approximately 1 year. Many institutional reports have shown that in selected patients, operative cytoreduction and hyperthermic intraoperative peritoneal chemotherapy using cisplatin or mitomycin C is associated with long-term survival. Recent studies on the molecular biology of DMPM have yielded new insights relating to the potentially important role of the phosphatidylinositol 3-kinase/mammalian target of rapamycin and epidermal growth factor receptor pathways in this disease, which may translate into new therapeutic options for patients with DMPM.