5-AZA and ATRA in Treating Patients with PSA-only Recurrent Prostate Cancer
Most men are diagnosed with prostate cancer at an early stage and can be cured with surgery and/or radiation therapy. However for some men, the cancer spreads to other parts of the body called metastasis, which can be lethal. There are several new effective therapies for metastatic disease, but cancer cells eventually become resistant to standard therapies. We need more knowledge to understand when and how cancer spreads to design better treatment strategies. It is well known that cancer cells can disseminate to other parts of the body, known as disseminated tumor cells (DTCs), even before a diagnosis of cancer is made. Thus, understanding DTCs can uncover more knowledge about how the cancer cells survive in a dormant (sleeping) state and become active to form lethal cancers. At our institution, scientists have identified certain blood markers that can detect when dormant cells are present. More importantly, a combination of approved drugs, Azacitidine (5-AZA) and All-trans retinoic acid (ATRA), can reprogram active cancer cells to become dormant, and thus render them inactive. In current practice, after patients receive treatment with surgery and/or radiation therapy, we monitor patients with a blood test, called prostate-specific antigen (PSA), to check for signs of cancer recurrence. Such monitoring leads to the identification of men that have PSA-only (biochemical) recurrence, which is defined as those having rising PSA without any evidence of symptoms or cancer seen on radiographic scans. Androgen deprivation therapy (ADT), or hormonal therapy, is the standard therapy in this case however the optimal timing for initiation of ADT remains controversial. Additionally, ADT causes side effects such as hot flashes, loss of libido, decreased muscle mass, fatigue, and osteoporosis, which can significantly lower the quality of life in men with otherwise no symptoms. 5-AZA and ATRA have been studied individually in prostate cancer with some evidence of activity and were overall well-tolerated. As such, we will test if the combination of 5-AZA + ATRA can inactive prostate cancer cells and maintain the cancer in a silent state. In order to confirm our scientific findings in the clinical trial patients, we will test our novel blood markers of dormancy while patients are receiving the treatment.