Impact of 10% Dose Reductions and Duration of Treatment Delays in the Management of Chemotherapy-Induced Neutropenia in Dogs Treated With Common Chemotherapy Protocols: A Single-Centre Experience

Abstract

Neutropenia is a common chemotherapy-associated adverse event (AE) in dogs and a significant cause of decreased relative dose intensity. Dose reductions (DRs) and treatment delays (TDs) are frequently applied to decrease the risk of further neutropenic events (NEs) and AEs, but there is no standardised approach. The two main objectives of this retrospective study were to determine: (1) the failure rate of a 10% DR to prevent a subsequent inadequate absolute neutrophil count (ANC), defined as a nadir ANC <0.75 × 109/L or pretreatment ANC <1.5 × 109/L; and (2) if the duration of TDs due to pretreatment neutropenia affects the occurrence of subsequent NEs. A total of 1056 chemotherapy treatments were recorded for 128 dogs that developed at least one NE. In 75 of 124 (60.5%, 95% CI: 51.2%–69%) evaluable NEs, a nadir ANC of ≥0.75 × 109/L and pretreatment ANC of ≥1.5 × 109/L were achieved after a single 10% chemotherapy DR, while a 10% DR failed to prevent a subsequent inadequate ANC in the remaining 49/124 (39.5%, 95% CI: 30.1%–48.3%). The only variable associated with failure was the drug prescribed. DR failure occurred in 22/39 (56.4%, 95% CI: 40.9%–70.6%) lomustine DRs, 14/27 (51.9%, 95% CI: 33.9%–69.2%) cyclophosphamide DRs, but only 2/22 (9.1%, 95% CI: 2.5%–27.8%) doxorubicin DRs and 2/24 (8.3%, 95% CI: 2.3%–25.8%) vincristine DRs. Seventy-three evaluable TDs (mean: 5 days, SD ± 2.2 days) were prescribed. There was no association between TD duration and subsequent NEs (p = 0.11).