Pheochromocytoma

Carboplatin & Paclitaxel (CP)

CP: Carboplatin & Paclitaxel

Regimen

Study	Dates of enrollment	Evidence	Comparator	Comparative Efficacy
Forde et al. 2022 (CheckMate 816)	2017-2019	Phase 3 (C)	1a. CP & Nivolumab 1b. CVb & Nivolumab 1c. DC & Nivolumab	Inferior EFS

Note: there were additional comparator options depending on histology; see the respective histology-specific pages for more details. This study was conducted in the United States. The reason for the study was that an unanswered question at the time was whether adding an immune checkpoint inhibitor would improve outcomes.

Biomarker eligibility criteria

• CheckMate 816: No sensitizing EGFR or ALK mutations

Chemotherapy

• Carboplatin (Paraplatin) AUC 5 or 6 IV once on day 1
• Paclitaxel (Taxol) 175 or 200 mg/m² IV once on day 1

21-day cycle for 3 cycles

Subsequent treatment

• Complete resection

References

1. CheckMate 816: Forde PM, Spicer J, Lu S, Provencio M, Mitsudomi T, Awad MM, Felip E, Broderick SR, Brahmer JR, Swanson SJ, Kerr K, Wang C, Ciuleanu TE, Saylors GB, Tanaka F, Ito H, Chen KN, Liberman M, Vokes EE, Taube JM, Dorange C, Cai J, Fiore J, Jarkowski A, Balli D, Sausen M, Pandya D, Calvet CY, Girard N; CheckMate 816 Investigators. Neoadjuvant Nivolumab plus Chemotherapy in Resectable Lung Cancer. N Engl J Med. 2022 May 26;386(21):1973-1985. Epub 2022 Apr 11. link to original article dosing details in manuscript have been reviewed by our editors PubMed NCT02998528

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3 regimens on this page 5 variants on this page

Guidelines

NCCN

• NCCN Guidelines - Neuroendocrine Tumors

All lines of therapy

Cyclophosphamide, Vincristine, Dacarbazine

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CVD: Cyclophosphamide, Vincristine, Dacarbazine

Regimen

Study	Evidence
Averbuch et al. 1988	Pilot, <20 pts

Chemotherapy

• Cyclophosphamide (Cytoxan) 750 mg/m² IV once on day 1
• Vincristine (Oncovin) 1.4 mg/m² IV once on day 1
• Dacarbazine (DTIC) 600 mg/m² IV once per day on days 1 & 2

21-day cycles

References

1. Averbuch SD, Steakley CS, Young RC, Gelmann EP, Goldstein DS, Stull R, Keiser HR. Malignant pheochromocytoma: effective treatment with a combination of cyclophosphamide, vincristine, and dacarbazine. Ann Intern Med. 1988 Aug 15;109(4):267-73. link to original article contains protocol PubMed

¹³¹I-Metaiodobenzylguanidine (¹³¹I-MIBG)

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Also known as m-[131I]iodobenzylguanidine ([131I]MIBG).

Regimen #1

Study	Evidence
Rose et al. 2003	Pilot, <20 pts

Patients underwent stem cell harvest prior to treatment in case autologous stem cell infusion was needed.

Radiotherapy

• ¹³¹I-Metaiodobenzylguanidine (¹³¹I-MIBG) 12 to 18 mCi/kg (maximum single dose of 850 mCi) IV over 2 hours once on day 1

Supportive medications

• Intravenous fluids started 12 hours before 131I-MIBG administration.
• Potassium iodide (KI) 6 mg/kg PO once at least 2 hours prior to 131I-MIBG, then potassium iodide (KI) 0.88 mg/kg PO Q4H x 7 days, then potassium iodide (KI) 1 mg/kg PO (frequency not specified) "for 45 days after the infusion."
• Potassium perchlorate 8 mg/kg once at least 2 hours prior to 131I-MIBG, then potassium perchlorate 2 mg/kg PO Q6H x 5 days.

"Repeat 131I-MIBG treatments were administered on a case-by-case basis in an effort to improve the overall response"

Regimen #2

Study	Evidence
Krempf et al. 1991	Pilot, <20 pts

Radiotherapy

• m-[131I]iodobenzylguanidine ([131I]MIBG) 740 megabequerel/mg every 3 months

References

1. Krempf M, Lumbroso J, Mornex R, Brendel AJ, Wemeau JL, Delisle MJ, Aubert B, Carpentier P, Fleury-Goyon MC, Gibold C et al. Use of m-[131I]iodobenzylguanidine in the treatment of malignant pheochromocytoma. J Clin Endocrinol Metab. 1991 Feb;72(2):455-61. link to original article contains protocol PubMed
2. Rose B, Matthay KK, Price D, Huberty J, Klencke B, Norton JA, Fitzgerald PA. High-dose 131I-metaiodobenzylguanidine therapy for 12 patients with malignant pheochromocytoma. Cancer. 2003 Jul 15;98(2):239-48. link to original article contains verified protocol PubMed