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. 2023 Nov-Dec;37(6):2402-2409.
doi: 10.1111/jvim.16875. Epub 2023 Oct 3.

Individualized chemotherapy drug dose escalation in dogs with multicentric lymphoma

Jacob M Siewert  1 , Daniel L Gustafson  1   2 , Kristen M Weishaar  1 , Annie M Galloway  3 , Douglas H Thamm  1   2
Affiliations

Individualized chemotherapy drug dose escalation in dogs with multicentric lymphoma

Jacob M Siewert et al. J Vet Intern Med. 2023 Nov-Dec.

Abstract

Background: This study was performed to determine the ability to escalate drug doses in a 15-week CHOP protocol in dogs with multicentric lymphoma.

Hypothesis: We hypothesized that at least 50% of dogs could successfully be escalated in at least 1 drug. Secondary aims were to establish objective response rate (ORR), progression-free interval (PFI), and overall survival time (OST).

Animals: Thirty dogs with newly diagnosed multicentric lymphoma were prospectively treated with a 15-week CHOP protocol.

Methods: This was a prospective cohort study. Drug doses that did not cause dose-limiting adverse effects (AEs) were increased using a standardized escalation protocol. AEs and response were assessed using VCOG criteria. Serial blood samples were collected after the first dose of each drug for pharmacokinetic analysis.

Results: Of the 23 dogs with the opportunity to dose escalate, at least 1 drug was successfully escalated in 18 (78%). Vincristine was successfully escalated to 0.8 mg/m2 or higher in 11 dogs, cyclophosphamide to 300 mg/m2 or higher in 16 dogs, and doxorubicin to 35 mg/m2 or 1.4 mg/kg or higher in 9 dogs. Three of the 23 dogs (13%) were hospitalized at least once because of drug-induced AEs. Neutropenia was the most common dose-limiting toxicosis for all drugs. Peak doxorubicin concentrations were significantly lower in dogs where doxorubicin was successfully escalated. The objective response rate was 100%. The median progression free interval was 171 days. The median overall survival time was 254 days.

Conclusions: Drugs in the CHOP protocol can often be escalated safely with manageable AEs.

Keywords: CHOP; adverse effects; cancer; pharmacokinetics.

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Conflict of interest statement

Authors declare no conflict of interest.

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