Specialty Section for the Treatment of Pancreas Cancer
There are approximately 27,000 new cases of pancreatic cancer with approximately 26,000 deaths each year in the United States. The incidence of this cancer has been gradually rising over the past 50 years, ranking it as the fifth most common cause of cancer death. The survival rate for pancreatic cancer has remained unchanged over the last 2 decades. Only 0.4 to 4% of patients survive 5 years or more. Curative resection is possible only in selected patients (perhaps 10 - 15%), with the expectation of survival ranging from 6 to 20%. The survival differences may be related to stage of disease and patient selection by the surgeon. The median survival for patients with resectable disease ranges from 6 to 23 months, with an average of 13.5 months.
Despite this grim outcome, considerable progress has been made in the ability to stage the disease adequately, to reduce surgical morbidity and to increase the median survival with the use of combined treatment modalities. A study conducted by the Gastrointestinal Tumor Study Group demonstrated the efficacy of postoperative adjuvant chemotherapy with nearly double median survival of surgery plus chemotherapy vs. surgery alone (20 vs. 11 months respectively). Subsequently, results of several other investigators have been published that evaluate the role of preoperative and intraoperative irradiation. Although some improvement in the rates of local control has been achieved with occasional long-term survivors, recurrences of the tumor outside of the irradiation field remain the major disadvantage of this combined treatment modality.
Undoubtedly, the most exciting new agent being tested in pancreatic cancer is gemcitabine. Several positive trials have been reported with gemcitabine. In a phase II trial in patients with pancreatic tumors, the partial response rate was 11.4%, and the median survival time was 13 months. In another phase II trial, 63 patients previously treated with 5-FU-based regimen were given gemcitabine. Seventeen patients showed clinical benefit (27%). Subsequently, a trial comparing gemcitabine to 5-FU reported clinical benefit in 23.8% of patients treated with gemcitabine versus 4.8% of those treated with 5-FU. The median survival was 5.65 months versus 4.4 months, respectively. Gemcitabine is of interest not only because it produces partial antitumor responses, but also because it appears to improve quality of life by reducing pain, medication requirements and improving nutritional status.
We have instituted two new clinical research protocols using intraperitoneal gemcitabine. The first protocol will be offered to patients with resectable carcinoma of the pancreas. The objectives of this study are: (1) evaluate the toxicity and (2) determine the survival benefit of adjuvant heated intraoperative intraperitoneal chemotherapy with gemcitabine following resection for pancreatic carcinoma. This protocol also includes the study of the pharmacokinetics of gemcitabine in human blood, urine, peritoneal fluid and tissue. Patients with clinically localized carcinoma of the pancreas or periampullary region will undergo standard surgery followed by a 60 minute heated (42oC) intraoperative intraperitoneal abdominal wash with gemcitabine. These treatments are designed to eradicate microscopic residual disease from the resection site and nearby peritoneal surfaces. Gemcitabine will be given at the dose of 1000 mg/m2. A total of 33 patients will be treated. Our projection is that an additional 30% of the patients with resectable pancreatic cancer may survive using this combined treatment, and that the incidence of intraabdominal recurrence will decrease. As patients recur, we will document the pattern of failure after this treatment and compare this pattern to historical controls.
The second protocol will be offered to patients with unresectable carcinoma of the pancreas. The purpose of this study is to determine the efficacy and the adverse events associated with radiofrequency hyperthermia given concomitantly with a standard intravenous dose of gemcitabine in patients with unresectable pancreas cancer. Patients with a biopsy proven diagnosis of pancreas cancer will undergo optimal surgical palliation using choledochoenterostomy and/or gastrojejunostomy. In some patients surgical palliation may not be required. The patients will be treated with a standard intravenous dose of gemcitabine on a weekly basis as tolerated. At the time of chemotherapy infusion, the entire epigastric region will be heated to a maximal tolerable dose of hyperthermia. If the gemcitabine produces toxicity, then the weekly dose of hyperthermia should be continued as tolerated by the patient. The survival of patients in this experimental group will be compared to historical controls where patients were treated with intravenous gemcitabine alone.
Our clinical research pathway for pancreatic and periampullary carcinoma is outlined below.
