An Open-Label, Phase II Safety, Tolerability, Drug Level and Efficacy Trial of Quinacrine in Patients With Androgen-Independent Metastatic Prostate Cancer
Despite a modest improvement in survival with available chemotherapy treatments,
androgen-independent metastatic prostate cancer remains essentially incurable.
Several changes in gene function that characterize malignancy have been identified. For
example the p53 gene in normal tissue lessens the risk of cancer through growth arrest or
cell suicidal programs. Thus the silenced p53 gene present in cancer tissue contributes to
the growth of the cancer. In addition when the p53 gene is silenced, a cell survival
pathway, controlled by the NF-kB gene, is activated leading increased cell survival.
Quinacrine can activate p53 and inhibit NF-kB, thus reestablishing cell suicidal programs
and decreasing cell survival in cancer tissue. Moreover, quinacrine is effective against
several prostate tumor cell lines in vitro, and has anti-tumor effects against prostate
cancer xenografts in mice.
Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Efficacy of Quinacrine, Based on Prostate Specific Antigen (PSA) Response in Patients With Androgen-independent Metastatic Prostate Cancer
Patients who achieved a complete response (CR) or a partial response (PR) to therapy were allowed to continue to receive treatment until disease progression or unacceptable toxicity occurred, until the patient discontinued treatment for another reason, or for a total of 6 months. Patients who continued to show a CR or PR or who maintained stable disease (SD) after 6 months of therapy were to be allowed to continue therapy at the investigator's discretion.
End of treatment
Edwin Posadas, MD
University of Chicago Hospitals
United States: Food and Drug Administration