Compassionate Use of 131I-MIBG for Patients With Malignant Pheochromocytoma

Pheochromocytomas (PHEO) and paragangliomas (PGL) are rare tumors, with an incidence of 2-8
cases per million annually. These tumors develop in both children and adults. About 15-20%
metastasize. Chemotherapy for this tumor usually consists of a combination of
cyclophosphamide, vincristine, and dacarbazine delivered over two days and repeated every 3
weeks. Such combined chemotherapy is ineffective for the majority of patients with metastatic
PHEO/PGL. A few patients with malignant PHEO have experienced remissions with sunitinib, but
the drug may produce severe toxicity and the experience with that drug is limited. Those
patients who do experience a remission with chemotherapy must continue it indefinitely to
stay in remission. However, most such patients experience such severe side effects from the
chemotherapy (marrow suppression, neuropathy, etc) that their chemotherapy must be
discontinued. Thus, chemotherapy is either ineffective or intolerable for the vast majority
of patients with metastatic PHEO/PGL.

Inclusion Criteria:

- Diagnosis: Refractory or relapsed PHEO/PGL with original diagnosis based on tumor
histopathology or the finding of PHEO/PGL tumor cells in the bone marrow. The
diagnosis may also be based upon the presence of high plasma fractionated
metanephrines or high urine catecholamines/metanephrines with diagnostic MIBG uptake.

- Age: > 2 years and able to cooperate with radiation safety restrictions during therapy
period.

- Disease status: It must be determined that either the PHEO/PGL tumors are not amenable
to safe surgical resection or are metastatic. Disease evaluable by MIBG scan must be
present within 6 weeks of study entry and subsequent to any intervening therapy.

- Life Expectancy: greater than 3 months.

- Lanksy and Karnofsky Performance Status: 70% or higher.

- Prior Therapy: Patients may enter this study with or without having had other therapy
for recurrent tumor. Patients may be treated who have not had chemotherapy or
radiation therapy. Patients may also be treated who have failed to respond to standard
chemotherapy or radiation therapy. Patients must have fully recovered from the toxic
effects of any prior therapy. At least 2 weeks should have elapsed since any
anti-tumor therapy and the patient must meet hematologic criteria below. Three months
should have elapsed in the case of completing radiation to any of the following
fields: total craniospinal, total abdominal, whole lung, total body irradiation).
Cytokine therapy (eg G-CSF, GM-CSF, IL-6, erythropoietin) must be discontinued a
minimum of 24 hours prior to MIBG therapy. Prior 131I-MIBG therapy is allowed if > 8
weeks from previous treatment. Cumulative lifetime dose of 131I-MIBG, including the
planned treatment, should not exceed 36 mCi/kg.

- Liver function: bilirubin < 2x upper limit of normal (ULN). Exception: Gilbert
syndrome); AST < 10x ULN.

- Kidney function: Creatinine =< 2x ULN.

- Hematopoietic Criteria Patients must have adequate hematopoietic function (without
transfusion): ANC >750 x 10E9/L; Platelets >50 x 10E9/L if stem cells are not
available; if stem cells are available, the patient should be independent of platelet
transfusions with a platelet count of at least 20 x 10E9/L. Hemoglobin >10g/dl at time
of treatment (transfusion allowed). Patients with granulocytopenia and/or
thrombocytopenia due to tumor metastatic to the bone marrow may be eligible after
discussion with Dr. Fitzgerald or designee.

- Normal lung function as manifested by no dyspnea at rest or exercise intolerance, no
oxygen requirement.

- No clinically significant cardiac dysfunction, normal EKG and EJ >50%

Exclusion Criteria:

- Patients with disease of any major organ system that would compromise their ability to
withstand therapy. Any significant organ impairment should be discussed with the Study
Chair or Vice Chair prior to patient entry.

- Patients with proteinuria in the absence of urinary infection 4 weeks prior to the
planned treatment date.

- Because of the teratogenic potential of the study medications, no patients who are
pregnant or breast feeding will be allowed. Patients of childbearing potential must
practice an effective method of birth control while participating on this study, to
avoid possible pregnancy.

- Patients who are on hemodialysis.

- Patients with active infections that meet grade 3-4 toxicity criteria.