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15-05-2012 | Veterinary medicine | Article

Dose-intense chemotherapy shows promise for canine lymphoma

Abstract

Free abstract

MedWire News: Dose-intense chemotherapy for dogs with multicentric lymphoma is feasible and as effective as standard-intensity regimens, a retrospective study indicates.

Additionally, animals that experienced multiple treatment delays had significantly better outcomes than those with no such delays, an intriguing finding that merits further investigation.

The study, by Jenna Burton (Colorado State University, Fort Collins, USA) and team, involved 31 dogs with multicentric lymphoma treated with the so-called "CHOP" protocol, which comprises cyclophosphamide, doxorubicin, vincristine, and prednisone, and has been shown to be a highly effective treatment for canine lymphoma.

While standard CHOP is administered over 19 weeks, dogs in this study received a dose-intense version that was given over 15 weeks. The 15-week CHOP protocol was modified after it had been given to 13 dogs because of an increased frequency of hematologic toxicities.

In reality, the 15-week protocol took an average of 18.9 weeks to complete, note Burton et al writing in Veterinary and Comparative Oncology. Nineteen (61%) dogs were treated with a 15-week protocol as intended, while 12 (39%) were converted to a 19-week protocol because of the occurrence of adverse events.

For all dogs in the study, the overall response rate was 100% with 26 (84%) dogs experiencing a complete response and five (16%) dogs a partial response.

The median progression-free interval (PFI) was 140 days and median overall survival (OS) was 257 days, with no difference between dogs that received the original and modified versions of the 15-week CHOP protocol.

In terms of tolerability, 75 adverse events were documented in 26 dogs. More than two-thirds of adverse events were hematologic, most commonly neutropenia, while other less-common adverse events were gastrointestinal (anorexia, vomiting, diarrhea, enteritis), constitutional (lethargy, weight loss), and respiratory (pneumonia).

In all, three (9.8%) dogs were hospitalized due to chemotherapy-associated toxicity, 19 (61%) dogs needed one or more dose reductions, and 23 (74%) dogs had one or more delays to their scheduled dosing, secondary to the occurrence of adverse events.

In multivariate analysis, three factors were found to be significant independent predictors for both PFI and OS: hypercalcemia, thrombocytopenia, and experiencing two or more treatment delays. The latter was associated with a 3.13-fold increase in PFI and an 11.1-fold increase in OS compared with one or no treatment delays.

"For dogs that required two or more treatment delays, the increased sensitivity of normal tissues to the cytotoxic effects of chemotherapeutic agents, particularly the bone marrow compartment, allowed for titration of chemotherapy dose resulting in administration of a maximally tolerated protocol dose for these individuals," the researchers note.

By Joanna Lyford