Studies in humans and other animals have shown that the higher the chemotherapy dose, the more significant its tumor-treating effects. But often, high medication doses cause adverse effects, some of which could be life-threatening. And, in horses, it’s still not clear exactly what the optimal equine chemotherapy treatment dose is for most medications. This means horses with cancer might be receiving less medication than they need to effectively fight the tumors in their bodies.The good news is that researchers are getting closer to figuring out the unknowns by using a process called dose escalation.
“Dose escalation is a strategy of gradual dose increases with careful monitoring for toxicity used to determine the highest tolerated dose and, thereby, higher dose intensity (the active drug dose over time) and maximum efficacy,” said Daniela Luethy, DVM, a large animal internal medicine lecturer at the University of Pennsylvania School of Veterinary Medicine, in Kennett Square.
Luethy and colleagues recently studied the effects of cyclophosphamide (an alkylating agent that interferes with the cancer cell’s DNA and inhibits cancer cell growth) dose escalation in nine horses with lymphoma, a type of hematologic (blood) cancer. She presented the team’s findings at the 2018 American College of Veterinary Medicine Forum, held June 14-16 in Seattle, Washington.
In their retrospective study, the researchers evaluated the cyclophosphamide doses horses received and any adverse effects noted in their medical records. The horses’ initial doses ranged from 150 mg/m2 to 300 mg/m2 administered intravenously (IV) alongside furosemide, a diuretic.
“Cyclophosphamide may have some toxic effects on the urinary tract, and furosemide administration may minimize this risk,” Luethy explained.
Some horses also received other medications, including corticosteroids, the antiviral drug valacyclovir, and different chemotherapeutic agents (doxorubicin, L-asparaginase, vincristine, lomustine, cytosine arabinoside, and chlorambucil). Luethy said it’s unknown whether these medications could have impacted the horse’s reaction to dose escalation.
Luethy said veterinarians increased three of the horses’ cyclophosphamide doses: one to 310 mg/m2, one to 450 mg/m2, and one to 800 mg/m2. The only adverse reactions they noted were in the 800 mg/m2 horse, who experienced mild lethargy and hind-limb edema (fluid swelling), which resolved without treatment.
“This horse experienced no adverse effects at previous and subsequent cyclophosphamide doses of 750 mg/m2 or less,” Luethy said.
“These findings suggest that cyclophosphamide dose escalation can be used in equine lymphoma treatment to achieve higher chemotherapeutic dose intensity while minimizing adverse effects,” she said.
Luethy also noted that this research indicates that cyclophosphamide’s therapeutic dose might be higher than previously thought. More studies are needed to pinpoint the optimal dosing for horses, she said.
Owners of horses with lymphoma should work with their veterinarians, internists, and oncologists to determine the best treatment dose and frequency for their animals.