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Epigenetic agent and vitamin A preparation help weakened patients with acute myeloid leukemia for whom intensive chemotherapy is too strenuous / Publication of the nationwide study in the Journal of Clinical Oncology

Acute myeloid leukemia (AML) is the most common form of acute blood cancer in adults and mainly occurs in people over the age of 65. However, patients in this age group in particular often cannot be treated with stressful chemotherapy due to concomitant illnesses or poor general health. Researchers at the University Medical Center Freiburg have now investigated promising combination therapies in a nationwide study. The additional administration of one of the therapies was able to extend the average survival time compared to the comparative therapy from five to eight months - without causing additional side effects. The study was published on December 3, 2019 in the Journal of Clinical Oncology.

"We were very surprised that the combination therapy helped the patients so significantly. However, it is at least as important that we have identified a weak point in the tumor where we can attack the cancer," says study leader Prof. Dr. Michael Lübbert, senior physician at the Department of Internal Medicine I at the Freiburg University Medical Center. A total of 200 patients were treated at 27 centers in Germany. The study was funded by the Federal Ministry of Education and Research with around two million euros.

Reprogramming the genetic material of degenerated cells

The medication used, decitabine and the vitamin A preparation tretinoin, are so-called epigenetically active substances. They do not attack the genetic material itself, but activate certain genes that can slow down the uncontrolled growth of cancer cells. "By 'reprogramming' the degenerated cell, the active substances reactivate those factors that inhibit cancer growth and allow the cell to mature or drive it to cell death," explains Lübbert. How exactly tretinoin works is still the subject of research. "There are indications that the cancer cells become resistant to decitabine therapy more slowly as a result of the vitamin A preparation," says the hematologist-oncologist.

The study was initiated and driven by academic researchers. Tretinoin has been used for decades in the treatment of a particular form of AML, and decitabine has also been approved since 2012, so this novel combination therapy offers an innovative approach for the treatment of older AML patients using familiar drugs whose side effects have been very well studied. A follow-up study to further optimize the therapy is already being planned.

Original title of the publication: Valproate and Retinoic Acid in Combination with Decitabine in Elderly Non-fit Acute Myeloid Leukemia Patients: Results of a Multicenter, Randomized 2x2 Phase II Trial
DOI: 10.1200/JCO.19.01053
Link to publication: https: //www.ncbi.nlm.nih.gov/pubmed/31794324

Title of the study: "Study of Decitabine Alone or in Combination With Valproic Acid and All-trans Retinoic Acid in Acute Myeloid Leukemia (DECIDER)"
Link to the study: https://clinicaltrials.gov/ct2/show/NCT00867672

Contact: 
Prof. Dr. Michael Lübbert
Department of Internal Medicine I (Focus: Hematology, Oncology and Stem Cell Transplantation)
University Medical Center Freiburg
Phone: 0761 270-36190