Personalized Management of Pheochromocytoma and Paraganglioma

. 2021 Jun 19;43(2):199–239. doi: 10.1210/endrev/bnab019

Practical tip/synthesis (applies to all clusters):
• Whenever possible, curative surgery should be the therapy of choice. • At least 7-14 days before surgery, other medical procedures (such as endoscopy), or systemic therapies, alpha-adrenoceptor blockade should be initiated in biochemically positive cases, unless this is purely elevated dopamine/3-methoxytyramine. • Surgery of a primary tumor in a patient with metastatic disease may be considered if there is a mass effect or reason to decrease high catecholamine levels to alleviate their organ-related damage/dysfunction. • Figure 4 summarizes a therapy flow-chart which suggests a potential sequence of therapy for a practicing physician, including dosing. • For rapidly progressive PPGLs, the recommended first-line therapy is chemotherapy (CVD scheme, or some would recommend temozolomide), and for slowly to moderately progressing PPGLs the recommended first-line therapy is radionuclide therapy—either with [¹³¹I]-MIBG or PRRT—depending on tumor uptake and location (1). • In the case of stable disease after 6 to 9 cycles of CVD chemotherapy, previously rapidly progressing PPGLs may be treated with prolonged chemotherapy (up to about 20 cycles) or de-escalated to temozolomide maintenance therapy. • In the case of progression to CVD chemotherapy, temozolomide monotherapy or temozolomide in combination with capecitabine (or a PARP inhibitor) may be chosen. In cases of poor tolerability, a metronomic scheme of temozolomide is possible. Alternatively, a TKI may be chosen. • In the case of progression of moderately growing PPGL following radionuclide therapy, if there is a high tumor burden then CVD chemotherapy should be considered. However, where the tumor burden is only moderate, temozolomide alone or in combination with capecitabine, or a TKI, may be more appropriate. • In the case of progression in response to temozolomide (+/- capecitabine) or a TKI, the alternative treatment can then be used. Following progression with both approaches, inclusion into a clinical trial or immunotherapy with pembrolizumab may be an option. • In some cases, active surveillance may be most appropriate if disease progression is slow.

Practical tip/synthesis (applies to all clusters):

• Whenever possible, curative surgery should be the therapy of choice.
• At least 7-14 days before surgery, other medical procedures (such as endoscopy), or systemic therapies, alpha-adrenoceptor blockade should be initiated in biochemically positive cases, unless this is purely elevated dopamine/3-methoxytyramine.
• Surgery of a primary tumor in a patient with metastatic disease may be considered if there is a mass effect or reason to decrease high catecholamine levels to alleviate their organ-related damage/dysfunction.
• Figure 4 summarizes a therapy flow-chart which suggests a potential sequence of therapy for a practicing physician, including dosing.
• For rapidly progressive PPGLs, the recommended first-line therapy is chemotherapy (CVD scheme, or some would recommend temozolomide), and for slowly to moderately progressing PPGLs the recommended first-line therapy is radionuclide therapy—either with [¹³¹I]-MIBG or PRRT—depending on tumor uptake and location (1).
• In the case of stable disease after 6 to 9 cycles of CVD chemotherapy, previously rapidly progressing PPGLs may be treated with prolonged chemotherapy (up to about 20 cycles) or de-escalated to temozolomide maintenance therapy.
• In the case of progression to CVD chemotherapy, temozolomide monotherapy or temozolomide in combination with capecitabine (or a PARP inhibitor) may be chosen. In cases of poor tolerability, a metronomic scheme of temozolomide is possible. Alternatively, a TKI may be chosen.
• In the case of progression of moderately growing PPGL following radionuclide therapy, if there is a high tumor burden then CVD chemotherapy should be considered. However, where the tumor burden is only moderate, temozolomide alone or in combination with capecitabine, or a TKI, may be more appropriate.
• In the case of progression in response to temozolomide (+/- capecitabine) or a TKI, the alternative treatment can then be used. Following progression with both approaches, inclusion into a clinical trial or immunotherapy with pembrolizumab may be an option.
• In some cases, active surveillance may be most appropriate if disease progression is slow.