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Metronomic Chemotherapy in Dogs

Traditionally chemotherapy is administered at the maximum tolerated dose followed by a break period to allow normal tissues to recover.


How does it work?

Current evidence suggests that the mechanism of action is by inhibition of blood supply to the tumour (anti-angiogenenic effects) and by positive stimulation of the anti-tumour immune response. The dose of chemotherapy given is generally too low to directly kill cancer cells. 


What responses are expected?

Durable stable disease or partial responses are considered a successful response to treatment. 


How is metronomic chemotherapy administered?

Metronomic chemotherapy is administered orally. Chemotherapy agents need to be compounded to an appropriate dose for the patient as they cannot be opened, split or crushed. Gloves should be worn when handling the capsules and sensible health and safety precautions taken with excreta as for traditional chemotherapy protocols.

COX-2 inhibitors (e.g. meloxicam, firocoxib) also form an important part of metronomic chemotherapy protocols due to their additional anti-angiogenic effects. These are prescribed at standard doses to be given orally alongside daily cyclophosphamide. 


How is metronomic chemotherapy used in veterinary patients?

There are several studies evaluating the use of metronomic chemotherapy in dogs. Unfortunately the number of patients reported in each study is small and the treatment protocols and patient monitoring are variable. Tumour types with responses reported include soft tissue sarcomas, splenic hemangiosarcoma and urinary bladder transitional cell carcinoma.

Unfortunately there is less published literature evaluating the use of metronomic chemotherapy in cats with different tumour types. One small study, whose primary goal was to evaluate toxicity, reported partial responses and stable diseases in various tumour types. Importantly, low toxicity was also reported.


What about monitoring and side effects?

Haematology, biochemistry and urine analysis should be performed at baseline and then every 4-6weeks.

Toxicity due to metronomic chemotherapy is uncommon. The low doses of chemotherapy drugs should not cause neutropenia or other changes on serum biochemistry or haematology analysis. Gastrointestinal adverse effects are also very uncommon. In dogs, sterile haemorrhagic cystitis following prolonged low dose, cyclophosphamide administration is reported. For this reason regular urine analysis is recommended.


To conclude…

With appropriate patient selection metronomic chemotherapy is a useful treatment option. It is best considered for patients where a rapid or large reduction in tumour size is not required for good quality of life. Benefits to treatment include low cost, low toxicity and ease of administration. It is worth considering in patients where other treatment has been declined or ineffective and where stable disease would be associated with good quality of life.

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