CHOP Chemotherapy Protocol for Canine Lymphoma

CHOP is the multiagent regimen “widely accepted as gold standard 1st-line treatment” for canine nodal lymphoma: cyclophosphamide (C), hydroxydaunorubicin, i.e. doxorubicin (H), vincristine (Oncovin) (O), and prednisolone or prednisone (P). It is most commonly prescribed as a 25-week (CHOP-25) or 19-week (CHOP-19) schedule and often given with L-asparaginase added (L-CHOP was the single most commonly used first-line B-cell protocol, 51%, in a 2009 Veterinary Cancer Society survey). In the largest direct comparison to date (a European multicenter retrospective cohort of 502 dogs with peripheral nodal B-cell lymphoma diagnosed at 16 referral centers between 2014 and 2021), median progression-free survival was 196 days with CHOP-19 versus 209 days with CHOP-25, and median overall survival was 302 versus 321 days, with no significant difference in PFS or OS between the two protocols.

What CHOP is and how it is used

CHOP is a four-drug combination, expanded in the recent comparison study as “C = cyclophosphamide, H = hydroxydaunorubicin [Doxorubicin], O = Oncovin, P = prednisolone” (Hawkes 2024); later publications expand the same combination as cyclophosphamide, doxorubicin, vincristine and prednisone (Angelo 2019). CHOP-25 and CHOP-19 are the most commonly prescribed versions (Hawkes 2024), but real-world protocols vary widely: in a written survey conducted at the 2009 Veterinary Cancer Society conference, the most commonly used first-line B-cell protocol combined L-asparaginase with cyclophosphamide, doxorubicin, vincristine and prednisone (L-CHOP, 51%), with CHOP alone used by 30% and other CHOP-based protocols by 12% of respondents, and reported protocol lengths ranging from ≤ 16 weeks to > 2 years (Regan 2013).

Published protocol outcomes

CHOP-19 versus CHOP-25 (Hawkes 2024). 502 dogs with peripheral nodal B-cell lymphoma diagnosed at 16 European oncology referral centers between 2014 and 2021: 155 received CHOP-19 and 347 received CHOP-25. Median progression-free survival was 196 days (95% CI, 176-233) with CHOP-19 versus 209 days (95% CI, 187-224) with CHOP-25; 6-month PFS was 56.5% versus 56.4% and 1-year PFS 14.1% versus 17%. Median overall survival was 302 days (95% CI, 249-338) versus 321 days (95% CI, 293-357); 1-year OS was 36.9% versus 42.8% and 2-year OS 13.5% versus 15.4%. No significant difference in PFS or OS was found, and the authors concluded both protocols could be used as a standard of care in future trials.

15-week dose-intense CHOP (Burton 2013). Thirty-one client-owned dogs with multicentric lymphoma treated with a 15-week dose-intense CHOP protocol had an overall response rate of 100% and a median progression-free interval of 140 days (95% CI, 91-335). Dogs with two or more treatment delays had significantly prolonged PFI and overall survival in multivariate analysis, while dose intensity did not correlate with outcome; the authors suggest dogs without adverse events may be underdosed and that future studies should focus on individual patient dose optimization.

Doxorubicin-based sequential combination chemotherapy (Keller 1993). Fifty-five dogs with lymphoma were treated with a doxorubicin-based sequential combination chemotherapy protocol: complete response in 46 dogs, partial response in 4, and no response in 5. The overall median remission duration was 36 weeks and median survival 51 weeks. On multivariate analysis, substage was the significant prognostic factor for remission duration (P = .036); substage (P = .006) and sex (P = .005) were significant for survival.

Where prednisone-only palliation fits

Prednisone alone: the Canine Lymphoma Steroid Only trial (Rassnick 2021). One hundred nine dogs with previously untreated, peripheral nodal, intermediate- or large-cell lymphoma recruited from 15 US institutions received prednisone at 40 mg/m2 PO once daily for 7 days, then 20 mg/m2 PO once daily thereafter. Median overall survival was 50 days (95% CI, 41-59). Survival was associated with substage (a versus b) and immunophenotype (B cell versus T cell). Owner-assigned quality-of-life scores at days 0 and 14 were significantly positively correlated with survival, and dogs with day-0 or day-14 QOL scores ≥ 50 had significantly longer survival times; no variable was predictive of long-term (> 120-day) survival. The authors position these data as information for the owner conversation at the time treatment decisions are made.

Doxorubicin plus prednisone, with or without L-asparaginase (Al-Nadaf 2018). In 33 dogs with high-grade B-cell lymphoma (31 evaluable), first-line doxorubicin and prednisone with or without L-asparaginase produced an overall response rate of 84%, median PFS of 147 days, median OS of 182 days, and a 1-year survival fraction of 23%. The authors conclude this is not a replacement for CHOP, but is an alternative when time and cost are limiting factors, providing therapeutic benefit greater than prednisone alone.

Clinical context and limitations

The CHOP-19/CHOP-25 figures above come specifically from dogs with peripheral nodal B-cell lymphoma. Phenotype matters: in a retrospective comparison of 73 dogs with multicentric T-cell lymphoma, hypercalcemia, or both, the CHOP-based treatment arm (50 dogs) had a median PFS of 133 days (Angelo 2019), materially shorter than the B-cell cohort figures. All CHOP outcome data cited here are retrospective (single-arm for Burton 2013 and Keller 1993; multicenter cohort for Hawkes 2024), and cross-protocol comparisons (for example, CHOP-25 median OS of 321 days versus 50 days with prednisone alone) are not head-to-head randomized comparisons; the populations differ in phenotype, substage, and era. The Regan data are a practice survey, not outcome data. Protocol drug doses and week-by-week schedules are deliberately omitted here; they are in the full texts of the cited papers.

Ask Vetinuity

For follow-up questions about CHOP-19 versus CHOP-25, dose intensity and treatment delays, or prednisone-only palliation, ask the Vetinuity clinical assistant.