Successful chemotherapy of hepatic metastases in a case of succinate dehydrogenase subunit B-related paraganglioma

Abstract

Compared to other familial pheochromocytoma/paragangliomas (PHEO/PGLs), the succinate dehydrogenase subunit B (SDHB)-related PHEO/PGLs often present with aggressive and rapidly growing metastatic lesions. Currently, there is no proven effective treatment for malignant PHEO/PGLs. Here, we present a 35-year-old white man with primary malignant abdominal extra-adrenal 11 cm paraganglioma underwent surgical successful resection. But 6 months later, he developed extensive bone, liver, and lymph nodes metastasis, which were demonstrated by computed tomography scan and the 18F-fluorodeoxyglucose positron emission tomography. However, his 123I-metaiodobenzylguanidine scintigraphy was negative; therefore, the cyclophosphamide, vincristine, and dacarbazine (CVD) combination chemotherapy was initiated. The combination chemotherapy was very effective showing 80% overall reduction in the liver lesions and 75% overall reduction in the retroperitoneal mass and adenopathy, and normalization of plasma catecholamine and metanephrine levels. However, plasma levels of dopamine (DA) and methoxytyramine (MTY) were only partially affected and remained consistently elevated throughout the remaining period of follow-up evaluation. Genetic testing revealed an SDHB gene mutation. Here, we present an SDHB-related PHEO/PGL patient with extensive tumor burden, numerous organ lesions, and rapidly growing tumors, which responded extremely well to CVD therapy. We conclude patients with SDHB-related PHEO/PGLs can be particularly sensitive to CVD chemotherapy and may have an excellent outcome if this therapy is used and continued on periodic basis. The data in this patient also illustrate the importance of measuring plasma levels of DA and MTY to provide a more complete and accurate assessment of the biochemical response to therapy than provided by measurements restricted to other catecholamines and O-methylated metabolites.

SDHB mutations are associated with response to temozolomide in patients with metastatic pheochromocytoma or paraganglioma

“…Interestingly, there was a significant difference in PFS between patients with mutation in SDHB (19.7 months), and patients without mutation in SDHB (2.9 months), suggesting that SDHB mutation may be a biomarker for temozolomide efficacy. Although a relationship between SDHB mutational status and TMZ response was previously suggested in case reports, our study is the first demonstration of such a relationship. Indeed, this study involves consecutive patients with different genetic statuses who were evaluated according to formalized criteria for the assessment of tumour response .…”

“…In a recent report from Japan, complete or partial biochemical and/or tumour responses were achieved in 47.1 % of 17 patients who had received CVD during a 23 year period . Anecdotal reports suggest that the efficacy of chemotherapy may be high in patients with mutations in SDHB . However, the use of CVD polychemotherapy in patients with MPP has not been validated by any prospective study.…”

“…13 Anecdotal reports suggest that the efficacy of chemotherapy may be high in patients with mutations in SDHB. 14,15 However, the use of CVD polychemotherapy in patients with MPP has not been validated by any prospective study. In addition, the efficacy of either vincristine or cyclophosphamide as a single agent to treat patients with MPP has not been validated.…”

Treatment of malignant phaeochromocytoma with a combination of cyclophosphamide, vincristine and dacarbazine: own experience and overview of the contemporary literature

“…Other studies had methodological differences with respect to the particular drugs applied 12,14 or provided limited imaging data on tumour response [11][12][13][16][17][18][19][20][21] ; the remaining articles are shown in Table 3. 8,9,15,[22][23][24][25][26][27][28][29][30][31][32][33] Apart from the more recent study by Ayala-Ramirez et al, 12 it has to be pointed out that the cohorts of these reports were rather small, with a maximum of 18 patients in one study 15 and <60 patients in total.…”

Metastatic Paraganglioma

“…Particularly in women and patients with primary PHEO, CVD is counter-indicated 88. However, in a patient with SDHB mutation related disease, great results were achieved under the CVD regimen 89. Thus, CVD therapy may be considered in patients with fast growing tumors due to SDHB mutation, in patients where tumor shrinkage prior to resection is required or in patients whose symptoms related to catecholamine excess cannot be managed otherwise 90.…”