Continued Tumor Reduction of Metastatic Pheochromocytoma/Paraganglioma Harboring Succinate Dehydrogenase Subunit B Mutations with Cyclical Chemotherapy

• Published in: Cellular and molecular neurobiology 2018-07, Vol.38 (5), p.1099-1106
• Main Authors: Jawed, Irfan, Velarde, Margarita, Därr, Roland, Wolf, Katherine I., Adams, Karen, Venkatesan, Aradhana M., Balasubramaniam, Sanjeeve, Poruchynsky, Marianne S., Reynolds, James C., Pacak, Karel, Fojo, Tito
• Format: Article
• Language: English
• Subjects: Adolescent; Adult; Biomedical and Life Sciences; Biomedicine; Cell Biology; Chemotherapy; Computed tomography; Cyclophosphamide; Dacarbazine; Dehydrogenases; Female; Fluorodeoxyglucose F18; Humans; Male; Metastases; Metastasis; Middle Aged; Mutation; Mutation - genetics; Neoplasm Metastasis; Neurobiology; Neurosciences; Original Paper; Paraganglioma; Paraganglioma - diagnostic imaging; Paraganglioma - drug therapy; Paraganglioma - enzymology; Paraganglioma - pathology; Patients; Pheochromocytoma; Pheochromocytoma - diagnostic imaging; Pheochromocytoma - drug therapy; Pheochromocytoma - enzymology; Pheochromocytoma - pathology; Positron emission tomography; Succinate dehydrogenase; Succinate Dehydrogenase - genetics; Succinate Dehydrogenase - metabolism; Treatment Outcome; Vincristine; Young Adult
• ISSN: 0272-4340; 1573-6830
• DOI: 10.1007/s10571-018-0579-4

Patients harboring germline mutations in the succinate dehydrogenase complex subunit B (SDHB) gene present with pheochromocytomas and paragangliomas (PPGL) that are more likely malignant and clinically aggressive. The combination chemotherapy cyclophosphamide, vincristine, and dacarbazine (CVD) was retrospectively evaluated in patients with SDHB -associated metastatic PPGL.Query Twelve metastatic PPGL patients harboring SDHB mutations/polymorphisms with undetectable SDHB immunostaining were treated with CVD. CVD therapy consisted of 750 mg/m 2 cyclophosphamide with 1.4 mg/m 2 vincristine on day 1 and 600 mg/m 2 dacarbazine on days 1 and 2, every 21–28 days. Treatment outcome was determined by RECIST criteria as well as determination of response duration and progression-free and overall survivals. A median of 20.5 cycles (range 4–41) was administered. All patients had tumor reduction (12–100% by RECIST). Complete response was seen in two patients, while partial response was observed in 8. The median number of cycles to response was 5.5. Median duration of response was 478 days, with progression-free and overall survivals of 930 and 1190 days, respectively. Serial [ 18 F]-fluorodeoxyglucose positron emission tomography and computed tomography imaging demonstrated continued incremental reduction in maximal standardized uptake values (SUV max ) values in 26/30 lesions. During treatment administration, the median SUV decreased from > 25 to