CytRx Corporation (Nasdaq:CYTR), a biopharmaceutical research and development company specializing in oncology, today announced that positive preclinical results from an in vivo study of aldoxorubicin in an animal model of glioblastoma will be presented at the American Association for Cancer Research Annual Meeting being held April 5-9, 2014 in San Diego, CA.
CytRx announced data from the trial, which demonstrated that aldoxorubicin significantly increased survival almost 2½ fold compared to doxorubicin treatment in an
xenograft tumor model employing growth of human glioblastoma multiforme (GBM) tumors in mouse brains. Aldoxorubicin, but not doxorubicin, also demonstrated preferential accumulation and prolonged retention in the tumor tissue. These data, combined with aldoxorubicin’s favorable safety profile, support the current evaluation of aldoxorubicin as a treatment for patients with GBM tumors.
“In addition to the clear survival benefit seen in the aldoxorubicin-treated animals, we also saw significant tumor regression and evidence of drug retention inside the tumors,” said Om Prakash, Ph.D., Research Professor of Medicine, Stanley S. Scott Cancer Center, Louisiana State University Health Sciences Center, New Orleans, the study’s principal investigator, and the poster presenter. “Aldoxorubicin also significantly reduced the number of dividing cells within the tumors and showed a statistically relevant increased expression of apoptosis biomarkers. In comparison, doxorubicin did not appear to enter the tumor to any significant degree and showed no efficacy greater than saline in the treatment of these brain tumors.”
CytRx is currently conducting a Phase 2 clinical trial evaluating aldoxorubicin in patients with late-stage GBM. In late 2013, the Company reported highly statistically significant results from its global Phase 2b clinical trial evaluating aldoxorubicin as a first-line therapy in patients with soft tissue sarcomas. In this trial, aldoxorubicin demonstrated 80-100% superiority over doxorubicin in progression-free survival (PFS). Median PFS, 6-month PFS and overall response rates all significantly favored aldoxorubicin treatment over doxorubicin. Aldoxorubicin is also being studied in a Phase 2 clinical trial in HIV-related Kaposi’s sarcoma. CytRx also has initiated, under a special protocol assessment, a pivotal Phase 3 global trial with aldoxorubicin as a therapy for patients with soft tissue sarcomas.
| Poster presentation details:
| Poster Title: Antitumor efficacy of a novel anthracycline derivative aldoxorubicin in an orthotopic mouse model of glioblastoma
| Abstract #: 816
| Date and Time: Sunday, April 6, 2014 from 1:00 to 5:00 PM PT
| Session ID: Experimental and Molecular Therapeutics 6
| Location: Hall A-E, Poster section 34
| Summary of the data: GBM is the most common and malignant of all primary brain tumors with a median survival of only 12-15 months despite standard-of-care treatments like surgical resection, radiotherapy, and chemotherapy. This study evaluated the preclinical efficacy of aldoxorubicin, a novel albumin-binding prodrug of doxorubicin, for the treatment of GBM in a murine model, and compared its antitumor effect with doxorubicin. Human glioma cells were injected in vivo into the left striatum. After 12 days, mice (n=8 in each group) received either vehicle (saline), a single intravenous injection of aldoxorubicin (24 mg/kg) or doxorubicin (6 mg/kg) once a week. The study results demonstrated that the animals treated with aldoxorubicin had a median survival of more than 60 days, compared to 26 days for the control animals or those treated with doxorubicin. The aldoxorubicin treated animals also demonstrated tumor regression. Fluorescence microscopy showed selective accumulation of aldoxorubicin, but not doxorubicin, in the tumor tissues resected from tumor-bearing mice 24h following intravenous injection of these drugs. HPLC analysis revealed 3- to 4-fold higher aldoxorubicin retention in the tumor tissues than in the surrounding brain tissues. Immunohistochemical evaluation of aldoxorubicin-treated tumors showed that the drug also significantly decreased the number of dividing cells and activated the apoptosis effector cleaved caspase-3.
Glioblastoma is the most common and most malignant brain tumor in adults and afflicts more than 12,000 new patients in the U.S. annually. Despite surgical resection, radiotherapy and chemotherapy, the median survival after diagnosis is approximately 12 to 14 months. Limited efficacy of chemotherapeutic agents has been attributed to several contributing factors including insufficient drug delivery to the tumor site through the blood-brain barrier.