Arsenic trioxide as a radiation sensitizer for (131)I-metaiodobenzylguanidine therapy: Results of a phase II study Journal Article
| Authors: | Modak, S.; Zanzonico, P.; Carrasquillo, J. A.; Kushner, B. H.; Kramer, K.; Cheung, N. K. V.; Larson, S. M.; Pandit-Taskar, N. |
| Article Title: | Arsenic trioxide as a radiation sensitizer for (131)I-metaiodobenzylguanidine therapy: Results of a phase II study |
| Abstract: | Arsenic trioxide has in vitro and in vivo radiosensitizing properties. We hypothesized that arsenic trioxide would enhance the efficacy of the targeted radiotherapeutic agent 131I-metaiodobenzylguanidine (131I-MIBG) and tested the combination in a phase II clinical trial. Methods: Patients with recurrent or refractory stage 4 neuroblastoma or metastatic paraganglioma/pheochromocytoma (MP) were treated using an institutional review board-approved protocol (Clinicaltrials.gov identifier NCT00107289). The planned treatment was 131I-MIBG (444 or 666 MBq/kg) intravenously on day 1 plus arsenic trioxide (0.15 or 0.25 mg/m2) intravenously on days 6-10 and 13-17. Toxicity was evaluated using National Cancer Institute Common Toxicity Criteria, version 3.0. Response was assessed by International Neuroblastoma Response Criteria or (for MP) by changes in 123I-MIBG or PET scans. Results: Twenty-one patients were treated: 19 with neuroblastoma and 2 with MP. Fourteen patients received 131I-MIBG and arsenic trioxide, both at maximal dosages; 2 patients received a 444 MBq/kg dose of 131I-MIBG plus a 0.15 mg/kg dose of arsenic trioxide; and 3 patients received a 666 MBq/kg dose of 131IMIBG plus a 0.15 mg/kg dose of arsenic trioxide. One did not receive arsenic trioxide because of transient central line-induced cardiac arrhythmia, and another received only 6 of 10 planned doses of arsenic trioxide because of grade 3 diarrhea and vomiting with concurrent grade 3 hypokalemia and hyponatremia. Nineteen patients experienced myelosuppression higher than grade 2, most frequently thrombocytopenia (n 5 18), though none required autologous stem cell rescue. Twelve of 13 evaluable patients experienced hyperamylasemia higher than grade 2 from transient sialoadenitis. By International Neuroblastoma Response Criteria, 12 neuroblastoma patients had no response and 7 had progressive disease, incluDing 6 of 8 entering the study with progressive disease. Objective improvements in semiquantitative 131I-MIBG scores were observed in 6 patients. No response was seen in MP. Seventeen of 19 neuroblastoma patients continued on further chemotherapy or immunotherapy. Mean 5-year overall survival (±SD) for neuroblastoma was 37% ± 11%. Mean absorbed dose of 131I-MIBG to blood was 0.134 cGy/MBq, well below myeloablative levels in all patients. Conclusion: 131IMIBG plus arsenic trioxide was well tolerated, with an adverse event profile similar to that of 131I-MIBG therapy alone. The addition of arsenic trioxide to 131I-MIBG did not significantly improve response rates when compared with historical data with 131I-MIBG alone. © 2016 by the Society of Nuclear Medicine and Molecular Imaging, Inc. |
| Keywords: | neuroblastoma; radiosensitization; mibg therapy; malignant pheochromocytoma/paraganglioma |
| Journal Title: | Journal of Nuclear Medicine |
| Volume: | 57 |
| Issue: | 2 |
| ISSN: | 0161-5505 |
| Publisher: | Society of Nuclear Medicine |
| Date Published: | 2016-02-01 |
| Start Page: | 231 |
| End Page: | 237 |
| Language: | English |
| DOI: | 10.2967/jnumed.115.161752 |
| PROVIDER: | scopus |
| PUBMED: | 26742708 |
| PMCID: | PMC4976822 |
| DOI/URL: | |
| Notes: | Article -- Export Date: 3 March 2016 -- Source: Scopus |
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311Kushner -
650Cheung -
236Kramer -
249Modak -
342Pandit-Taskar -
355Zanzonico -
140Carrasquillo -
959Larson
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