Malignant pheochromocytomas and paragangliomas: a phase II study of therapy with high-dose 131I-metaiodobenzylguanidine (131I-MIBG).
Thirty patients with malignant pheochromocytoma (PHEO) or paraganglioma (PGL) were treated with high-dose 131I-MIBG. Patients were 11-62 (mean 39) years old: 19 patients males and 11 females. Nineteen patients had PGL, three of which were multifocal. Six PGLs were nonsecretory. Eleven patients had PHEO. All 30 patients had prior surgery. Fourteen patients were refractory to prior radiation or chemotherapy before 131I-MIBG. Peripheral blood stem cells (PBSCs) were collected and cryopreserved. 131I-MIBG was synthesized on-site, by exchange-labeling 131I with 127I-MIBG in a solid-phase Cu2+-catalyzed exchange reaction. 131I-MIBG was infused over 2 h via a peripheral IV. Doses ranged from 557 mCi to 1185 mCi (7.4 mCi/kg to 18.75 mCi/kg). Median dose was 833 mCi (12.55 mCi/kg). Marrow hypoplasia commenced 3 weeks after 131I-MIBG therapy. After the first 131I-MIBG therapy, 19 patients required platelet transfusions; 19 received GCSF; 12 received epoeitin or RBCs. Four patients received a PBSC infusion. High-dose 131I-MIBG resulted in the following overall tumor responses in 30 patients: 4 sustained complete remissions (CRs); 15 sustained partial remissions (PRs); 1 sustained stable disease (SD); 5 progressive disease (PD); 5 initial PRs or SD but relapsed to PD. Twenty-three of the 30 patients remain alive; deaths were from PD (5), myelodysplasia (1), and unrelated cause (1). Overall predicted survival at 5 years is 75% (Kaplan Meier estimate). For patients with metastatic PHEO or PGL, who have good *I-MIBG uptake on diagnostic scanning, high-dose 131I-MIBG therapy was effective in producing a sustained CR, PR, or SD in 67% of patients, with tolerable toxicity.
Fitzgerald
Paul A
PA
Department of Medicine, UCSF Comprehensive Cancer Center, Box 1222, University of California, San Francisco, San Francisco, CA 94143-1222, USA. paul.fitzgerald@ucsf.edu
Goldsby
Robert E
RE
Huberty
John P
JP
Price
David C
DC
Hawkins
Randall A
RA
Veatch
Janet J
JJ
Dela Cruz
Filemon
F
Jahan
Thierry M
TM
Linker
Charles A
CA
Damon
Lloyd
L
Matthay
Katherine K
KK
D019797:3-Iodobenzylguanidine / Q000009:adverse effects / Q000627:therapeutic use*; D000293:Adolescent; D000310:Adrenal Gland Neoplasms / Q000175:diagnosis / Q000378:metabolism / Q000532:radiotherapy*; D000328:Adult; D002648:Child; D003937:Diagnosis, Differential; D004307:Dose-Response Relationship, Radiation; D005260:Female; D006801:Humans; D007457:Iodine Radioisotopes / Q000009:adverse effects / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D010235:Paraganglioma / Q000175:diagnosis / Q000532:radiotherapy*; D010673:Pheochromocytoma / Q000175:diagnosis / Q000378:metabolism / Q000532:radiotherapy*
D007457:Iodine Radioisotopes; D019797:3-Iodobenzylguanidine