Cyclophosphamide, an alkylating agent, is commonly included in chemotherapeutic protocols for equine neoplasia, including lymphoma. Dosages regularly used in equine chemotherapeutic protocols are extrapolated from other species, and cyclophosphamide dose optimization has not been reported in horses. Dose intensity refers to the dose of active drug over time; and multiple studies in humans and animals with cancer have shown that increasing chemotherapeutic dose intensity correlates with increased anti-tumor effect. Chemotherapeutic drug dose escalation is a strategy of gradual dose increases with careful monitoring for toxicity, utilized to determine the highest tolerated dose and thereby achieve higher dose intensity and maximum efficacy. The purpose of this report was to describe cyclophosphamide dose escalation during equine chemotherapy. Nine horses were included following medical record search and case recruitment via the ACVIM LAIM and Oncology Diplomate listserves. Seven horses had multicentric lymphoma and two horses had cutaneous lymphoma. T-cell rich large B-cell lymphoma was the most common immunohistochemical classification (n = 6). Initial dose of cyclophosphamide ranged from 150 mg/m2 to 300 mg/m2 IV and furosemide was administered concomitantly. Other drugs administered included doxorubicin, L-asparaginase, vincristine, lomustine, cytosine arabinoside, chlorambucil, valacyclovir, and corticosteroids. Cyclophosphamide dose was escalated in 3 horses to maximum doses of 310mg/m2 IV, 450 mg/m2 IV, and 800 mg/m2 IV. Adverse effects attributed to cyclophosphamide administration were noted in one horse. This horse developed VCOG-CTCAE grade 1 lethargy and pelvic limb edema following a cyclophosphamide dose of 800 mg/m2; these signs resolved without treatment. This horse experienced no adverse effects at previous and subsequent cyclophosphamide doses ≤ 750 mg/m2 IV. Two pregnant mares received cyclophosphamide at doses of 150 mg/m2 and 300 mg/m2 without adverse reactions or apparent detrimental effects on fetal health. These findings suggest that cyclophosphamide dose escalation may be used in treatment of equine lymphoma to achieve higher chemotherapeutic dose intensity while minimizing adverse effects. The therapeutic dose of cyclophosphamide may be higher in horses than previously used and further studies are warranted to determine the optimal dose of cyclophosphamide for horses.
Resident, Large Animal Internal Medicine
University of Pennsylvania School of Veterinary Medicine New Bolton Center
Thursday, June 14
11:45 AM – 12:00 PM
Thursday, June 14
12:00 PM – 12:15 PM
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