PMID- 37787577 OWN - NLM STAT- MEDLINE DCOM- 20231121 LR - 20231129 IS - 1939-1676 (Electronic) IS - 0891-6640 (Print) IS - 0891-6640 (Linking) VI - 37 IP - 6 DP - 2023 Nov-Dec TI - Individualized chemotherapy drug dose escalation in dogs with multicentric lymphoma. PG - 2402-2409 LID - 10.1111/jvim.16875 [doi] AB - 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/m(2) or higher in 11 dogs, cyclophosphamide to 300 mg/m(2) or higher in 16 dogs, and doxorubicin to 35 mg/m(2) 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. CI - (c) 2023 The Authors. Journal of Veterinary Internal Medicine published by Wiley Periodicals LLC on behalf of American College of Veterinary Internal Medicine. FAU - Siewert, Jacob M AU - Siewert JM AUID- ORCID: 0009-0002-3046-5127 AD - Flint Animal Cancer Center, Colorado State University, Fort Collins, Colorado, USA. FAU - Gustafson, Daniel L AU - Gustafson DL AD - Flint Animal Cancer Center, Colorado State University, Fort Collins, Colorado, USA. AD - University of Colorado Comprehensive Cancer Center, Aurora, Colorado, USA. FAU - Weishaar, Kristen M AU - Weishaar KM AUID- ORCID: 0000-0003-2827-2246 AD - Flint Animal Cancer Center, Colorado State University, Fort Collins, Colorado, USA. FAU - Galloway, Annie M AU - Galloway AM AD - Colorado Animal Specialty & Emergency, Boulder, Colorado, USA. FAU - Thamm, Douglas H AU - Thamm DH AUID- ORCID: 0000-0002-8914-7767 AD - Flint Animal Cancer Center, Colorado State University, Fort Collins, Colorado, USA. AD - University of Colorado Comprehensive Cancer Center, Aurora, Colorado, USA. LA - eng GR - Eldred Foundation/ PT - Journal Article DEP - 20231003 PL - United States TA - J Vet Intern Med JT - Journal of veterinary internal medicine JID - 8708660 RN - 80168379AG (Doxorubicin) SB - IM MH - Humans MH - Dogs MH - Animals MH - Prospective Studies MH - *Lymphoma/drug therapy/veterinary MH - *Neutropenia/veterinary MH - Doxorubicin/adverse effects MH - *Dog Diseases/drug therapy PMC - PMC10658528 OTO - NOTNLM OT - CHOP OT - adverse effects OT - cancer OT - pharmacokinetics COIS- Authors declare no conflict of interest. EDAT- 2023/10/03 12:42 MHDA- 2023/11/21 06:42 PMCR- 2023/10/03 CRDT- 2023/10/03 09:23 PHST- 2023/05/03 00:00 [received] PHST- 2023/09/11 00:00 [accepted] PHST- 2023/11/21 06:42 [medline] PHST- 2023/10/03 12:42 [pubmed] PHST- 2023/10/03 09:23 [entrez] PHST- 2023/10/03 00:00 [pmc-release] AID - JVIM16875 [pii] AID - 10.1111/jvim.16875 [doi] PST - ppublish SO - J Vet Intern Med. 2023 Nov-Dec;37(6):2402-2409. doi: 10.1111/jvim.16875. Epub 2023 Oct 3.