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Clinician's Brief (Capsule)


|October 2015

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Lymphoma is the most common hematopoietic neoplasm of dogs. Negative pretreatment prognostic indicators have been reported (eg, hypercalcemia, pretreatment with corticosteroids); however, prognostic indicators following chemotherapy are less well-known. A common adverse effect of chemotherapy is myelosuppression. In humans, chemotherapy-induced neutropenia is positively correlated with patient outcomes for various solid tumors.

In this study, 50 newly diagnosed dogs with multicentric lymphoma were treated with CHOP-based (cyclophosphamide, hydroxydaunorubicin, vincristine, prednisolone) protocols. CBCs, toxicity, remission, and survival times were monitored. Of 50 dogs, 13 had treatment-associated neutropenia (neutrophils <3000/µL), which was found to be a positive predictive indicator. All dogs in the neutropenia group achieved complete remission (CR). In the nonneutropenia group, 27/37 (73%) achieved CR, 7 (19%) had partial remission, and 3 (8%) had stable disease.

The median first remission durations of the neutropenia and nonneutropenia groups were 812 and 219 days, respectively. Median survival times in the neutropenia and nonneutropenia groups were 952 and 282 days, respectively. Dogs in the neutropenia group had significantly lower body weights than dogs in the nonneutropenia group. No neutropenia-related clinical signs (eg, fever, sepsis) occurred. Eleven of 13 dogs with neutropenia and 32/37 dogs without neutropenia showed GI toxicity, but this was self-limiting with only 2 dogs requiring hospitalization. The authors propose that given these results, individual chemotherapy dosages should be gradually adjusted upward to achieve neutropenia without unacceptable toxicity, thus potentially lengthening first remission durations and survival times.

Global Commentary

Chemotherapeutic agents classically work on “the more drug you give, the more cells you kill” principle with the limitation being that the drug administered kills healthy multiplying cells as well as neoplastic ones. This gives rise to the concept of a maximum tolerated dose (MTD), the highest dose that can be given before causing unacceptable adverse effects. This paper suggests that the closer you can get to an individual animal’s MTD, the more successful the outcome. However, the difference in amount of drug given between the neutropenic and nonneutropenic group when calculated on a mg/kg basis (using the mean body weights cited) is about 20%. Additionally, cyclophosphamide is often given as a tablet that should not be broken, which means there is a wide variation in dose given. Thus, safely increasing the dose in general practice is not as easy as it may seem.—Sue Murphy, BVM&S, MSc (Clin Onc) DECVIM-CA (Onc), MRCVS

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