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J Clin Endocrinol Metab. 2017 Nov 1. doi: 10.1210/jc.2017-02030. [Epub ahead of print]

Phase 1 Study of High-Specific-Activity I-131 MIBG for Metastatic and/or Recurrent Pheochromocytoma or Paraganglioma.

Author information

1
Department of Diagnostic Imaging, Warren Alpert Medical School of Brown University, Providence, Rhode Island, 02903.
2
Department of Radiology, University of Pennsylvania Health System, Philadelphia, Pennsylvania, 19104.
3
Progenics Pharmaceuticals, Inc., New York, New York, 10007.
4
Radiology and Medicine, Weill Medical College of Cornell University, New York, New York, 10065.

Abstract

Context:

There are no approved therapies for the treatment of metastatic and/or recurrent pheochromocytoma or paraganglioma (PPGL) in the United States.

Objective:

To determine the maximum tolerated dose (MTD) of high-specific-activity I-131 meta-iodobenzylguanidine (MIBG) for the treatment of metastatic and/or recurrent PPGL.

Design:

Phase 1, dose escalating study to determine the MTD via a standard 3+3 design; escalating by 37 MBq/kg starting at 222 MBq/kg.

Setting:

Three centers.

Patients:

Twenty-one patients were eligible, received study drug, and were evaluable for MTD, response, and toxicity.

Intervention:

Open-label use of high-specific-activity I-131 MIBG therapy.

Main Outcome Measures:

Dose-limiting toxicities, adverse events, radiation absorbed dose estimates, radiographic tumor response, biochemical response, and survival.

Results:

The MTD was determined to be 296 MBq/kg based on two observed dose-limiting toxicities at the next dose level. The highest mean radiation absorbed dose estimates were in the thyroid and lower large intestinal wall (each 1.2 mGy/MBq). Response was evaluated by total administered activity: four (19%) patients, all of whom received >18.5 GBq of study drug, had radiographic tumor responses of partial response by RECIST. Best biochemical responses (complete or partial response) for serum chromogranin A and total metanephrines were observed in 80% and 64% of patients, respectively. Overall survival was 85.7% at 1 year and 61.9% at 2 years post-treatment. The majority (84%) of adverse events were considered mild or moderate in severity.

Conclusions:

These findings support further development of high-specific-activity I-131 MIBG for the treatment of metastatic and/or recurrent PPGL at a MTD of 296 MBq/kg.

PMID:
29099942
DOI:
10.1210/jc.2017-02030
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