Comparative Effectiveness of COP and CHOP Chemotherapy Protocols in Feline Intermediate‐ to Large‐Cell Lymphoma: A Systematic Review and Meta‐Analysis

Feline intermediate‐ to large‐cell lymphoma is commonly treated with COP or CHOP chemotherapy, but the clinical benefit of adding doxorubicin (CHOP) remains controversial given its associated toxicity profile and cost. This systematic review and exploratory meta‐analysis summarized response and survival outcomes reported for COP‐ and CHOP‐based protocols in feline intermediate‐ to large‐cell lymphoma. Searching PubMed, Scopus, and CAB Abstracts (2000–2024), we included 21 studies comprising 1054 cats. An exploratory random‐effects meta‐analysis utilizing Restricted Maximum Likelihood (REML) estimation was conducted to evaluate overall (ORR), complete (CR), and partial response (PR) rates. The overall pooled ORR was 81.0%. Subgroup meta‐regression revealed no statistically significant differences between COP and CHOP for ORR (83.0% vs. 77.0%, p = 0.360), CR (57.0% vs. 49.0%, p = 0.350), or PR (28.0% vs. 22.0%, p = 0.468). Profound heterogeneity (overall I 2 = 85.4%–89.6%) persisted across all analyses, driven primarily by the pooling of diverse anatomical subtypes and uncontrolled confounding by Feline Leukaemia Virus (FeLV) status. Furthermore, inadequate variance reporting and a widespread lack of standardized response criteria (e.g., VCOG‐RECIST) precluded a formal meta‐analysis of survival outcomes. Descriptively, reported median survival times ranged broadly (COP: 108–610 days; CHOP: 62–973 days) without a clear advantage for CHOP. A custom weighted risk‐of‐bias assessment highlighted significant methodological deficiencies across the literature. In conclusion, current aggregate evidence does not demonstrate a statistically detectable difference in response rates between CHOP‐ and COP‐based protocols. Severe methodological heterogeneity and retrospective selection bias prevent definitive conclusions regarding long‐term survival, emphasizing the critical need for homogeneous, prospective randomized trials utilizing standardized reporting guidelines.