Phase II study of high-dose [131I]metaiodobenzylguanidine therapy for patients with metastatic pheochromocytoma and paraganglioma.
OBJECTIVE
To evaluate the safety and efficacy of high-dose [(131)I]metaiodobenzylguanidine ([(131)I]MIBG) in the treatment of malignant pheochromocytoma (PHEO) and paraganglioma (PGL).


METHODS
Fifty patients with metastatic PHEO or PGL, age 10 to 64 years, were treated with [(131)I]MIBG doses ranging from 492 to 1,160 mCi (median, 12 mCi/kg). Cumulative [(131)I]MIBG administered ranged from 492 to 3,191 mCi. Autologous hematopoietic stem cells were collected and cryopreserved before treatment with [(131)I]MIBG greater than 12 mCi/kg or with a total dose greater than 500 mCi. Sixty-nine [(131)I]MIBG infusions were given, which included infusions to 35 patients treated once and infusions to 15 patients who received two or three treatments. Response was evaluated by [(123)I]MIBG scans, computed tomography/magnetic resonance imaging, urinary catecholamines/metanephrines, and chromogranin A.


RESULTS
The overall complete response (CR) plus partial response (PR) rate in 49 evaluable patients was 22%. Additionally, 35% of patients achieved a CR or PR in at least one measure of response without progressive disease, and 8% of patients maintained stable disease for greater than 12 months. Thirty-five percent of patients experienced progressive disease within 1 year after therapy. The estimated 5-year overall survival rate was 64%. Toxicities included grades 3 to 4 neutropenia (87%) and thrombocytopenia (83%). Grades 3 to 4 nonhematologic toxicity included acute respiratory distress syndrome (n = 2), bronchiolitis obliterans organizing pneumonia (n = 2), pulmonary embolism (n = 1), fever with neutropenia (n = 7), acute hypertension (n = 10), infection (n = 2), myelodysplastic syndrome (n = 2), and hypogonadism (n = 4).


CONCLUSIONS
Although serious toxicity may occur, the survival and response rates achieved with high-dose [(131)I]MIBG suggest its utility in the management of selected patients with metastatic PHEO and PGL.
Gonias
Sara
S
Department of Pediatrics, University of California, San Francisco, 350 Parnassus Ave, Suite 710, San Francisco, CA 94117, USA.
Goldsby
Robert
R
Matthay
Katherine K
KK
Hawkins
Randall
R
Price
David
D
Huberty
John
J
Damon
Lloyd
L
Linker
Charles
C
Sznewajs
Aimee
A
Shiboski
Steve
S
Fitzgerald
Paul
P
D019797:3-Iodobenzylguanidine / Q000008:administration & dosage* / Q000009:adverse effects; D000293:Adolescent; D000310:Adrenal Gland Neoplasms / Q000175:diagnosis / Q000401:mortality / Q000532:radiotherapy* / Q000556:secondary; D000328:Adult; D014408:Biomarkers, Tumor / Q000652:urine; D002395:Catecholamines / Q000652:urine; D002648:Child; D053379:Chromogranin A / Q000652:urine; D018572:Disease-Free Survival; D004307:Dose-Response Relationship, Radiation; D005260:Female; D006801:Humans; D007262:Infusions, Intravenous; D007457:Iodine Radioisotopes / Q000008:administration & dosage* / Q000009:adverse effects; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D010235:Paraganglioma / Q000175:diagnosis / Q000532:radiotherapy* / Q000556:secondary; D010673:Pheochromocytoma / Q000175:diagnosis / Q000401:mortality / Q000532:radiotherapy* / Q000556:secondary; D016016:Proportional Hazards Models; D011446:Prospective Studies; D019275:Radiopharmaceuticals / Q000008:administration & dosage* / Q000009:adverse effects; D018570:Risk Assessment; D013997:Time Factors; D016896:Treatment Outcome; D055815:Young Adult
D014408:Biomarkers, Tumor; D002395:Catecholamines; D053379:Chromogranin A; D007457:Iodine Radioisotopes; D019275:Radiopharmaceuticals; D019797:3-Iodobenzylguanidine