Response‐based modification of CHOP chemotherapy for canine B‐cell lymphoma

Abstract

Despite high initial response rates, a subset of dogs with B‐cell lymphoma responds less robustly to CHOP‐based chemotherapy and experiences shorter survival. One hundred and four dogs with nodal B‐cell lymphoma were treated with a response‐based CHOP (RBCHOP) protocol modified based on response to individual drugs during the first chemotherapy cycle. Dogs achieving complete (CR) or partial response (PR) at week 3, following treatment with vincristine and cyclophosphamide, received RBCHOP 1 (n = 72), a protocol sequentially rotating vincristine, cyclophosphamide, and doxorubicin. Dogs without a detectable response at week 3 that subsequently achieved CR or PR following treatment with doxorubicin received RBCHOP 2 (n = 14), in which four doses of doxorubicin were given consecutively followed by vincristine and cyclophosphamide. Dogs that failed to respond at week 3 and then to doxorubicin at week 5 assessment were offered rescue chemotherapy (RBCHOP 3, n = 18). Median progression free survival (PFS) and overall survival time (OST) were similar between RBCHOP 1 (PFS 210 days, OST 354 days) and RBCHOP 2 (PFS 220 days, OST 456 days), but significantly shorter for RBCHOP 3 (PFS 34 days, OST 80.5 days, P < 0.001). No presenting signalment nor hematologic variable differentiated patient cohort, however, dogs in RBCHOP 2 and RBCHOP 3 were more likely to have a lymphocytosis at diagnosis (P = 0.02 and 0.04, respectively). Protocol modification based on response during the first cycle resulted in similar toxicity profiles and outcomes to previously published variants of CHOP, and prognosis remained poor for dogs failing to respond during the first treatment cycle.

Prognostic indicators for naïve canine non‐indolent T‐cell lymphoma treated with combination lomustine, vincristine, procarbazine and prednisolone chemotherapy

“…In this cohort, continued use of the LOPP protocol was only recommended for those that achieved CR, and a failure to respond to therapy or relapse of disease would necessitate change in protocol or discontinuation of therapy. A failure to respond to chemotherapeutic agents is well reported as a negative prognostic indicator, and this study supports these findings 21,25,47 …”

“…A failure to respond to chemotherapeutic agents is well reported as a negative prognostic indicator, and this study supports these findings. 21,25,47 Overall, the LOPP protocol used in this study was well tolerated.…”

P-Glycoprotein Activity at Diagnosis Does Not Predict Therapy Outcome and Survival in Canine B-Cell Lymphoma

“…Another study reported 121 cases treated by chemotherapy, with a median survival time (MST) of 300 days (range 1–1644 days) [ 50 ]. In yet another study, median RFP was 196 days (range 22–1656 days) and OST was 292 days (range 40–2246 days) of dogs receiving CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisolone) based protocols [ 51 ]. The time of first relapse (RFP) is an accurate indicator of survival statistics because it is not affected by variables influencing OST (such as non-lymphoma related diseases, for instance, accidents, heart disease, infections).…”

Bite-size introduction to canine hematologic malignancies

“…However, the majority of dogs relapse with resistant lymphoma and median survivals of 10-13 months are reported 5,37 . Although CHOP-based protocols are routinely used for B-and T-cell disease, there is some evidence that more alkylator heavy protocols are more efficacious against T-cell lymphoma however, appropriate randomized trials to test this have yet to be performed [38][39][40] . As responses to chemotherapy for high-grade T cell lymphoma are generally worse than those for high-grade B cell, protocol optimization for T cell disease is ongoing 5 .…”