July 16, 2018

AVMA 2018: Metronomic Chemotherapy - Another Treatment Option for Neoplasia

What is metronomic chemotherapy, and how does it differ from traditional chemotherapy?
By Kate Boatright, VMD

Chemotherapy offers pets with cancer the ability to live longer with better quality of life despite having a terminal disease. However, traditional chemotherapy protocols are not the right fit for every owner, patient, or disease process. A newer option called metronomic chemotherapy offers an alternative treatment, explained cancer specialist Sue Ettinger, DVM, DACVIM (oncology), at the 2018 American Veterinary Medical Association Convention in Denver, Colorado.

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Traditional chemotherapy protocols, also known as maximum tolerated dose, rely on giving high doses of cytotoxic drugs with the goal of direct tumor cell death. Breaks between treatments are essential to allow normal rapidly dividing tissues such as bone marrow and the gastrointestinal tract to recover, but those breaks also allow tumor cells to repopulate and develop drug resistance over time. Traditional protocols come with a variety of side effects, which veterinary oncologists work with owners to minimize and manage to maintain quality of life in their patients. Additionally, these protocols are often not successful in the face of gross metastatic disease.

In contrast, metronomic chemotherapy is “uninterrupted administration of low doses of cytotoxic drugs at regular and frequent intervals,” Dr. Ettinger said. Instead of destroying the tumor cells directly, this treatment interrupts tumor angiogenesis by targeting the quickly dividing endothelial cells in the vessel walls supplying tumors. The death of these cells prevents continued growth and metastasis as tumor cells cannot continue to divide without adequate blood supply. Due to the low doses and unique cell targets, toxicities to normal cells are minimized, and the continuous dosing prevents endothelial cell recovery. The primary goal of this treatment is to stabilize, not cure, disease.

Metronomic chemotherapy protocols use a combination of 2 to 3 drugs given orally at home on a daily or every-other-day basis. The first drug is a low-dose chemotherapeutic agent such as cyclophosphamide, chlorambucil, or lomustine. While low doses of these drugs minimize toxicity, their administration is not without risk. For example, sterile hemorrhagic cystitis is a known debilitating side effect of cyclophosphamide and has been seen even with low dose protocols. The second agent used is an anti-angiogenic medication such as a tyrosine kinase inhibitor (toceranib) or nonsteroidal anti-inflammatory drug. In some cases, doxycycline is added to the protocol for its anti-inflammatory effects.

Dr. Ettinger shared several remarkable success stories of metronomic chemotherapy from her practice, including patients that have survived (and thrived) for 3 to 4 years in the face of gross metastatic disease. She offer client handouts on metronomic chemotherapy on her website.

She cautioned that metronomic chemotherapy should not be used to replace the recognized standard of care in neoplastic disease. More research is needed to determine the ideal tumor targets as well as the best drugs and dose schedule to use. However, metronomic chemotherapy offers a promising option for patients living with metastatic disease and some incompletely resected neoplasms. As Dr. Ettinger says, we want our patients to “live longer, live well!”

 
Dr. Boatright is an associate veterinarian in western Pennsylvania. She graduated from the University of Pennsylvania in 2013 and currently works as a general practitioner and emergency veterinarian. Dr. Boatright is actively involved in her state and local veterinary medical associations and is a former national officer of the Veterinary Business Management Association.

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