Anti-tumor effects of nitrosylcobalamin against spontaneous tumors in dogs.

Abstract

PURPOSE:

Given the limited options available to treat canine cancers, the use of companion animals for evaluating new drugs may identify better therapies for veterinary and human oncology. The anti-tumor effects of nitrosylcobalamin (NO-Cbl), an apoptosis-inducing, vitamin B12-based carrier of nitric oxide (NO), was evaluated in four dogs with spontaneous cancer.

EXPERIMENTAL DESIGN:

(1) A 13 year-old female spayed Giant Schnauzer with inoperable thyroid carcinoma and hypercalcemia. (2) A 6 year-old male neutered Golden Retriever with a malignant peripheral nerve sheath tumor (MPNST). (3) A ten yr-old neutered male Bichon Frise with apocrine gland anal sac adenocarcinoma (AGACA). (4) A 7 year-old female spayed Labrador mix with spinal meningioma following partial surgical resection. Tumor regression was measured by physical exam and verified using ultrasound (case 1) and MRI (case 2-4). Serum chemistries and hematologic parameters were monitored throughout the studies.

RESULTS:

(1) The Giant Schnauzer demonstrated a 77% reduction in tumor volume after ten weeks of daily NO-Cbl treatment. (2) The Golden Retriever demonstrated a 53% reduction in tumor volume after 15 months of daily NO-Cbl therapy. (3) The Bichon Frise demonstrated a 43% regression of the primary tumor and a 90% regression of an iliac lymph node measured by MRI after 15 months of treatment. After 61 months, the dog currently has stable disease, normal liver enzymes, CBC analysis, and no evidence of toxicity. (4) The Labrador demonstrated complete regression of the residual tumor after 6 months of treatment.

CONCLUSION:

We have shown previously that NO-Cbl is endocytosed by malignant cells, resulting in intra-tumoral NO release. In this study, we have shown that daily long-term use of NO-Cbl induced responses in all dogs without any signs of toxicity. The use of NO-Cbl capitalizes on the tumor-specific properties of the vitamin B12 receptor and represents a promising anti-cancer therapy.

• Authors: Joseph A Bauer, Gerald Frye, Anne Bahr, Jennifer Gieg, Peter Brofman
• Journal: Investigational new drugs (Invest New Drugs) Vol. 28 Issue 5 Pg. 694-702 (Oct 2010) ISSN: 1573-0646 [Electronic] United States
• PMID: 19557306 (Publication Type: Case Reports, Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

• Antineoplastic Agents
• Nitroso Compounds
• nitrosylcobalamin
• Vitamin B 12

Topics

• Animals
• Antineoplastic Agents (metabolism, pharmacokinetics, therapeutic use)
• Dog Diseases (diagnostic imaging, drug therapy, pathology)
• Dogs
• Dose-Response Relationship, Drug
• Female
• Magnetic Resonance Imaging
• Male
• Neoplasms (diagnostic imaging, drug therapy, pathology, veterinary)
• Nitroso Compounds (metabolism, pharmacokinetics, therapeutic use)
• Tumor Burden
• Ultrasonography
• Vitamin B 12 (analogs & derivatives, metabolism, pharmacokinetics, therapeutic use)