Combination Epigenetic Therapy Has Efficacy in Patients with Refractory Advanced Non–Small Cell Lung Cancer

Combination Epigenetic Therapy Has Efficacy in Patients with Refractory Advanced Non–Small Cell Lung Cancer

1. 
   Rosalyn A. Juergens1,


2. 
   John Wrangle1,


3. 
   Frank P. Vendetti3,


4. 
   Sara C. Murphy1,


5. 
   Ming Zhao1,


6. 
   Barbara Coleman1,


7. 
   Rosa Sebree1,


8. 
   Kristen Rodgers2,


9. 
   Craig M. Hooker1,


10. 
    Noreli Franco1,


11. 
    Beverly Lee1,


12. 
    Salina Tsai4,


13. 
    Igor Espinoza Delgado5,


14. 
    Michelle A. Rudek1,


15. 
    Steven A. Belinsky6,


16. 
    James G. Herman1,


17. 
    Stephen B. Baylin1,


18. 
    Malcolm V. Brock2 and


19. 
    Charles M. Rudin1
    

+ Author Affiliations

1. 
   
   
   
   Authors’ Affiliations:¹Department of Oncology, ²Department of Surgery, ³Anti-Cancer Drug Development Graduate Training Program, and ⁴Department of Radiology, Johns Hopkins University, Baltimore, Maryland; ⁵Investigational Drug Branch, National Cancer Institute, Bethesda, Maryland; and ⁶Lovelace Respiratory Research Institute, Albuquerque, New Mexico
   
   

1. 
   Corresponding Authors:
   Charles M. Rudin, MD, PhD, Johns Hopkins University, Cancer Research Building 2, Room 544, 1550 Orleans Street, Baltimore, MD 21231. E-mail: rudin@jhmi.edu; or Malcolm V. Brock, MD, Johns Hopkins University, Cancer Research Building 1, Room 542, 1650 Orleans Street, Baltimore, MD 21231. E-mail: mbrock1@jhmi.edu
   

Abstract

Epigenetic alterations are strongly associated with the development of cancer. We conducted a phase I/II trial of combined epigenetic therapy with azacitidine and entinostat, inhibitors of DNA methylation and histone deacetylation, respectively, in extensively pretreated patients with recurrent metastatic non–small cell lung cancer. This therapy is well tolerated, and objective responses were observed, including a complete response and a partial response in a patient who remains alive and without disease progression approximately 2 years after completing protocol therapy. Median survival in the entire cohort was 6.4 months (95% CI 3.8–9.2), comparing favorably with existing therapeutic options. Demethylation of a set of 4 epigenetically silenced genes known to be associated with lung cancer was detectable in serial blood samples in these patients and was associated with improved progression-free (P = 0.034) and overall survival (P = 0.035). Four of 19 patients had major objective responses to subsequent anticancer therapies given immediately after epigenetic therapy.

Significance: This study demonstrates that combined epigenetic therapy with low-dose azacitidine and entinostat results in objective, durable responses in patients with solid tumors and defines a blood-based biomarker that correlates with clinical benefit. Cancer Discovery; 1(7); OF1–OF10. ©2011 AACR.

• 
  Received August 26, 2011.


• 
  Revision received September 26, 2011.


• 
  Accepted October 3, 2011.

• ©2011 American Association for Cancer Research.

Combination Epigenetic Therapy Has Efficacy in Patients with Refractory Advanced Non–Small Cell Lung Cancer

Underactive Thyroid and Heart Failure a Bad Combination: Study: MedlinePlus

Underactive Thyroid and Heart Failure a Bad Combination: Study: MedlinePlus

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Underactive Thyroid and Heart Failure a Bad Combination: Study

Hypothyroidism impact varies by race, with blacks at increased risk of death, findings suggest

URL of this page: http://www.nlm.nih.gov/medlineplus/news/fullstory_137089.html

 (*this news item will not be available after 08/20/2013)

By Mary Elizabeth Dallas

Wednesday, May 22, 2013

Related MedlinePlus Pages

• African American Health


• Heart Failure


• Thyroid Diseases

WEDNESDAY, May 22 (HealthDay News) — People with heart failure are more likely to experience poorer health from having a thyroid gland that is even mildly underactive, according to a new study.
And among black patients, the researchers found an increased risk of death linked to the condition, which is known as hypothyroidism.
“This study is the first to show that African-Americans who have hypothyroidism face a greater risk of death than patients of other racial and ethnic groups,” Dr. Connie Rhee, of Brigham and Women’s Hospital in Boston, said in a news release from the Endocrine Society. “This elevated risk exists despite the fact that hypothyroidism is less common in the African-American population compared to other groups.”
“More research is needed to confirm these findings and to determine the underlying reasons why hypothyroidism has a differential impact on people of different races and ethnicities,” Rhee said.
Hypothyroidism occurs when the thyroid doesn’t produce enough hormones. The researchers noted that people with mild forms of the condition have thyroid function at the low end of the normal range.
In conducting the study, Rhee and her colleagues analyzed information on about 750 patients with hypothyroidism, including nearly 700 people with a mild form of the condition.
Although it’s unclear why hypothyroidism has a different effect on people of various races and ethnicities, the study authors said doctors should not take a blanket approach to assessing people’s risk for the condition and determining whether they require treatment.
“Our data suggest that mild hypothyroidism may, in fact, be harmful in specific populations, including people with heart failure,” Rhee said in the news release. “A one-size-fits-all approach may not be appropriate for assessing risk and determining whether treatment is required for [mild] hypothyroidism.”
More than 9.5 million people in the United States have hypothyroidism, the study authors said.
The study is scheduled for publication in the June issue of the Journal of Clinical Endocrinology & Metabolism.

SOURCE: The Endocrine Society news release, May 22, 2013

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