SUN-932 Successful Response of Temozolomide (TMZ) in two Patients with Metastatic Pheochromocytoma/Paragangliomas (PPGLs)

Introduction: PPGLs are rare neuroendocrine tumors that arise from chromaffin cells of the adrenal medulla or their neural crest progenitors, being able to secrete catecholamines. Its treatment is primarily surgical; however, for metastatic/inoperable tumors, effective treatments are lacking. The use of TMZ, an oral alkylating agent, has been scarcely reported with variable response rates. We report 2 patients with reasonable clinical, biochemical and structural responses. Case Reports: Case 1) A 14-year old girl presented with neck pain, sweating, hypertension and tachycardia. Urinary hormonal profile revealed metanephrines 80 (up to 320 ug/24h) and normetanephrines 2983 (up to 390 ug/24h). Abdominal MRI showed a 10x6x5 cm retroperitoneal lesion in close contact with celiac trunk, superior mesenteric artery, renal arteries, aorta, left renal vein and vertebral bodies of T10, T11 and T12. A chest CT revealed multiple lung metastases. After 11 months, both the primary abdominal lesion and lung metastases increased in size.. Due to disease severity, after excluding surgical possibilities and confirming diagnosis by lesion biopsy, rescue treatment with TMZ was started for 5 days on a 28-day cycle. After 11 cycles, lung and abdominal lesions decreased more than 30% in size, and urinary metanephrines decreased 53.4%. After 21 cycles, there is no evidence of disease progression. Case 2) A 44-year old female was first diagnosed at the age of 31 with a right adrenal mass invading the kidney and the inferior vena cava associated with hypertension, sweating, headaches and palpitations. She underwent right adrenalectomy and nephrectomy. Immunohistochemistry confirmed the diagnosis of pheochromocytoma. Seven years later, follow-up CT`s showed a 3 x 2 cm liver metastasis, which was resected, and two lung lesions, one located at the right inferior lobe (1.6 cm) and the other at the left superior lobe (0.9 cm), which initially were just followed-up. At this time, a 7-month sorafenib trial was performed but the drug was stopped due to intolerable side effects. After 3 years of follow-up, the lung lesions increased in size and the right lesion was resected, but the patient refused surgery for the remainder left lung lesion. After 1 year, left lung lesion increased to 2.4 cm and mediastinal and paratracheal lymphadenomegaly developed. TMZ in the same aforementioned schedule was prescribed and after 7 cycles a new chest CT revealed complete regression of the lung and lymph node metastases.. Urinary metanephrines were 2.1 times the upper limit of normal before TMZ and decreased to normal range. Conclusion: These cases highlight the promising role of a well-tolerated single drug chemotherapy regimen in severe cases of metastatic and inoperable PPGLs. TMZ could be considered an alternative strategy for the treatment of these cases and, if possible, should be tested in adequate clinical trials.