Complete responses to mitotane in metastatic adrenocortical carcinoma - A new look at an old drug Journal Article

Authors: Reidy-Lagunes, D. L.; Lung, B.; Untch, B. R.; Raj, N.; Hrabovsky, A.; Kelly, C.; Gerst, S.; Katz, S.; Kampel, L.; Chou, J.; Gopalan, A.; Saltz, L. B.
Article Title: Complete responses to mitotane in metastatic adrenocortical carcinoma - A new look at an old drug
Abstract: Purpose. Based largely on reports that predate modern reporting standards, mitotane has been considered a systemic treatment option for both hormone control and antitumor control of metastatic adrenocortical cancer (ACC), although the therapeutic window is narrow. Methods. We searched electronic medical records to identify patients with metastatic ACC treated and prescribed singleagent mitotane at Memorial Sloan Kettering Cancer Center from March 15, 1989-September 18, 2015. Reference radiologists reviewed all imaging and determined efficacy according to Response Evaluation Criteria in Solid Tumors 1.1. Patient demographics, toxicities, and treatment outcomes were reviewed. Next-generation sequencing was performed in selected cases. Results. Thirty-six patients were identified. The mean age was 54 and 50% had functional tumors. Grade 3 or greater toxicities were documented in 16 out of 36 patients (44%) and 17% had documented long term adrenal insufficiency. Progression of the disease as the best response occurred in 30 out of 36 patients (83%) and one patient (3%) experienced clinical progression. Three patients achieved a complete response (CR) (8%), one patient achieved a partial response (3%), and one patient (3%) had stable disease after slow disease progression prior to initiation of therapy (durable for 6 months). All responders had nonfunctional tumors. Next-generation sequencing in two of the three CR patients was performed and failed to identify any novel alterations. Conclusion. In this retrospective series, mitotane had a low response rate and low tumor control rate; however, a disproportionately high complete response rate suggested it should be used in selected individuals. Adrenal insufficiency is common with mitotane use and aggressive treatment with steroid supplementation should be considered when appropriate to avoid excess toxicities. Biomarkers are desperately needed to further define this disease. © AlphaMed Press 2017.
Keywords: mitotane; adrenocortical carcinoma; adrenal insufficiency
Journal Title: The Oncologist
Volume: 22
Issue: 9
ISSN: 1083-7159
Publisher: AlphaMed Press  
Date Published: 2017-09-01
Start Page: 1102
End Page: 1106
Language: English
DOI: 10.1634/theoncologist.2016-0459
PROVIDER: scopus
PMCID: PMC5599197
PUBMED: 28559412
Notes: Article -- Export Date: 2 October 2017 -- Source: Scopus
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MSK Authors
  1. Joanne Fu-Lou Chou
    155 Chou
  2. Leonard B Saltz
    592 Saltz
  3. Lewis J Kampel
    11 Kampel
  4. Seth Stephen Katz
    16 Katz
  5. Diane Lauren Reidy
    149 Reidy
  6. Anuradha Gopalan
    274 Gopalan
  7. Scott R Gerst
    42 Gerst
  8. Brian Untch
    24 Untch
  9. Nitya Prabhakar Raj
    27 Raj
  10. Betty Ying-Feng Lung
    6 Lung
  11. Ciara Marie Kelly
    9 Kelly