Cellular and Molecular Neurobiology

, Volume 38, Issue 5, pp 1099–1106 | Cite as

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

  • Irfan Jawed
  • Margarita Velarde
  • Roland Därr
  • Katherine I. Wolf
  • Karen Adams
  • Aradhana M. Venkatesan
  • Sanjeeve Balasubramaniam
  • Marianne S. Poruchynsky
  • James C. Reynolds
  • Karel Pacak
  • Tito Fojo
Original Paper


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/m2 cyclophosphamide with 1.4 mg/m2 vincristine on day 1 and 600 mg/m2 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 [18F]-fluorodeoxyglucose positron emission tomography and computed tomography imaging demonstrated continued incremental reduction in maximal standardized uptake values (SUVmax) values in 26/30 lesions. During treatment administration, the median SUV decreased from > 25 to < 6, indicating the efficacy of chemotherapy over a prolonged period of time. Prolonged therapy results in continued incremental tumor reduction, and is consistent with persistent drug sensitivity. CVD chemotherapy is recommended to be considered part of the initial management in patients with metastatic SDHB-related PPGL.


Pheochromocytoma/paraganglioma Succinate dehydrogenase Cyclophosphamide Vincristine Dacarbazine 


Author Contributions

IJ, KP, and TF designed the study. MV, RD, KIW, KA, AMV, SB, MSP, and JCR were involved in data collection, analysis, and interpretation. All authors have read and approve the final version of this manuscript.


This work was supported by the Intramural Research Program of the National Institutes of Health; the Eunice Kennedy Shriver National Institute of Child Health and Human Development; and the German Research Foundation (DFG) (Grant Number DA 1630/1-1 to RD).

Compliance with Ethical Standards

Conflict of interest

The authors declare that they have no conflict of interest.

Ethical Approval

All procedures performed in studies involving human participants were in accordance with the ethical standards of the Institutional Review Board of the National Cancer Institute of the National Institutes of Health and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. This article does not contain any studies with animals performed by any of the authors.

Informed Consent

Informed consent was obtained from all individual participants included in the study.

Supplementary material

10571_2018_579_MOESM1_ESM.docx (199 kb)
Supplementary material 1 (DOCX 198 kb)


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Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2018

Authors and Affiliations

  • Irfan Jawed
    • 1
  • Margarita Velarde
    • 1
  • Roland Därr
    • 2
  • Katherine I. Wolf
    • 2
  • Karen Adams
    • 2
  • Aradhana M. Venkatesan
    • 3
  • Sanjeeve Balasubramaniam
    • 1
  • Marianne S. Poruchynsky
    • 1
  • James C. Reynolds
    • 4
  • Karel Pacak
    • 2
  • Tito Fojo
    • 1
  1. 1.Medical Oncology, National Cancer InstituteNational Institutes of HealthBethesdaUSA
  2. 2.Section on Medical Neuroendocrinology, Eunice Kennedy Shriver National Institute of Child Health and Human DevelopmentNational Institutes of HealthBethesdaUSA
  3. 3.Section of Abdominal Imaging, Department of Diagnostic RadiologyMD Anderson Cancer CenterHoustonUSA
  4. 4.Nuclear Medicine Division, Department of Radiology and Imaging Sciences, Clinical CenterNational Institutes of HealthBethesdaUSA

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