Interferon and Octreotide to Treat Zollinger-Ellison Syndrome and Advanced Non-B Islet Cell Cancer
Interferon and Octreotide to Treat Zollinger-Ellison Syndrome and Advanced Non-B Islet Cell Cancer
This study will examine the safety and effectiveness of interferon-a and octreotide for the
 treatment of Zollinger-Ellison syndrome (gastrinoma) and advanced non-B islet cell cancer.
 Gastrinoma is a tumor produced by the pancreas that secretes the hormone gastrin, which in
 turn stimulates production of gastric juices that cause ulcers. Some of these tumors are
 malignant. Gastrinomas that have spread and cannot be surgically removed require drug
 treatment (chemotherapy). Current drug regimens, however, provide only temporary benefit and,
 in some cases, produce life-threatening side effects. In studies of patients with tumors
 similar to gastrinoma, the drugs octreotide and interferon-a, alone or in combination, showed
 some effect in stopping tumor growth and were better tolerated than chemotherapy. At least
 one-third of patients responded to treatment with either drug for at least 6 months; the two
 drugs given together may produce a better response than either one alone.

 Patients currently enrolled in an NIH study of Zollinger-Ellison syndrome whose gastrinoma
 has spread from the original site and cannot be surgically removed may be eligible for this
 study.

 Participants will be admitted to the NIH Clinical Center for blood and urine tests,
 electrocardiogram (EKG), chest X-ray and imaging studies (CT, ultrasound, MRI, octreoscan,
 and bone scan) before beginning treatment to evaluate the size and extent of tumors. Patients
 will then start interferon-a or octreotide, or both, given as injections under the skin.
 Treatment will continue for at least 6 months, unless side effects require stopping the drugs
 early. Patients whose tumors shrink or remain stable may continue treatment indefinitely.
 Those who do not respond to treatment will be taken off the study and offered standard
 chemotherapy.

 Patients will be admitted to the hospital for the first day or two of therapy to be monitored
 for side effects and to learn how to self-inject the drugs to continue therapy at home. Both
 drugs are given [Note: how often? once a day, twice a day, weekly?] (Octreotide is also
 available in long-acting form, and patients who prefer may be given this drug once a month by
 the doctor.)

 During the treatment period, patients will be seen by their personal physician every 2 weeks
 for the first month and once a month thereafter for a medical evaluation and check of adverse
 side effects of treatment. In addition, they will be admitted to the NIH Clinical Center once
 every 3 months for a medical evaluation and imaging studies, including CT, MRI, ultrasound,
 bone scan, and octreoscan, to assess the effect of treatment on tumor size.
Heretofore morbidity and mortality in Zollinger-Ellison syndrome were caused by severe ulcer
 disease. The advent of specific drugs to cure ulcer disease now extends life until metastases
 from the non-B-islet cell tumor or other events cause death. Patients with metastatic
 gastrinoma that is not surgically resectable and that has increased in size over a 4-6 month
 period prior to the study will be treated with interferon-alpha, 5 million international
 units/day. The drug will be administered subcutaneously by the patient. Tumor response and
 side effects will be monitored. Patients will receive 6 months of therapy and if there is
 reduction or stabilization of tumor masses, therapy will continue as long as response is
 maintained.
-  INCLUSION CRITERIA

 Subjects selected for this study will be patients with Zollinger-Ellison syndrome who are
 being evaluated under the protocol entitled "Diagnostic evaluation of patients with
 suspected abnormalities of gastric secretion" (80-DK-123). To be entered into the study a
 patient must meet each of 3 criteria:

 1. histologically proven gastrinoma;

 2. evidence of metastatic tumor by one or more of angiography, ultrasound, computerized
 axial tomography, bone scan or octreoscan;

 3. progression of tumor size during the preceding 6 months as assessed by repeated
 imaging studies.

 EXCLUSION CRITERIA

 For treatment with interferon-(alpha):

 1. Congestive heart failure

 2. Proteinuria, 3 + or greater

 3. Creatinine clearance less than 30 ml/min

 4. Platelet count less than 30 x 10(9)/1

 5. White blood count less than 4 x 10(9)/1

 6. Bilirubin greater than 3 mg/dl

 7. Positive test for HIV antibody

 8. Pregnancy

 For treatment with octreotide:

 1. Presence of cholelithiases