Individualized chemotherapy drug dose escalation in dogs with multicentric lymphoma

Abstract

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

• adverse effects
• cancer
• CHOP
• pharmacokinetics