Impact of Chemotherapeutic Dose Intensity and Hematologic Toxicity on First Remission Duration in Dogs with Lymphoma Treated with a Chemoradiotherapy Protocol

Abstract

Background: Dose intensity has proven to be critical in maximizing chemotherapeutic efficacy for numerous human cancers. To date, the impact of dose intensity and toxicity on first remission duration has not been thoroughly assessed in dogs with lymphoma.Hypothesis: Dogs that receive maximal dose intensity will have prolonged first remission duration. Animals: Sixty-two dogs with lymphoma that were treated according to a standardized chemoradiotherapy regimen and achieved durable complete remissions were identified from the medical records database of North Carolina State University.Methods: Dosage reductions and treatment delays resulting from chemotherapy-related neutropenia were evaluated retrospectively, and each patient's actual summation dose intensity and frequency of myelotoxicity were calculated. Impact of dose intensity and frequency of neutropenia on first remission duration were evaluated by Cox proportional hazards regression.Results: Development of grade III or IV neutropenia during chemotherapy was found to be associated with prolonged first remission duration (P , .01). Dose intensity did not have a significant impact on remission duration (P 5 .07).Conclusions and Clinical Importance: Results of this study suggest that dosage reductions and treatment delays instituted to avoid repeated neutropenic episodes do not reduce first remission duration. Prolonged remission duration in patients that developed grade III or IV neutropenic episodes indicates the need for further optimization of dosing strategies for canine lymphoma patients undergoing chemotherapy.

Chemotherapy-induced neutropenia is associated with prolonged remission duration and survival time in canine lymphoma

“…This result is similar to studies involving doseintensified chemotherapy that investigated canine lymphoma (Vaughan et al, 2007;Sorenmo et al, 2010). One recent report revealed that dogs that needed dose reductions and treatment delays after chemoradiotherapy had longer remission durations.…”

“…One recent report revealed that dogs that needed dose reductions and treatment delays after chemoradiotherapy had longer remission durations. Dogs with no chemotherapy-induced myelosuppression had similarly nonresponsive tumour cells (Vaughan et al, 2007). Sorenmo et al (2010) reported similar findings.…”

“…Based on our research, only three reports have indicated increased remission duration or survival time (ST) in dogs with lymphoma that required dose reduction and treatment delays after being treated with chemoradiotherapy or dose-intensified chemotherapy protocols (Vaughan et al, 2007;Sorenmo et al, 2010;Burton et al, 2013). However, no studies have investigated the effects of chemotherapyinduced neutropenia in dogs with lymphoma treated with conventional dosages of chemotherapy.…”

“…These findings indicate that chemotherapy-induced neutropenia may be a useful indicator for predicting tumour responses. Vaughan et al (2007) used consolidated half-body radiation after chemotherapeutic induction, and Sorenmo et al (2010) simultaneously used vincristine and cyclophosphamide; however, these treatments are not routinely used in conventional chemotherapeutic protocols for canine lymphoma. Therefore, whether a similar result could be obtained without half-body radiation or the concurrent administration of cytotoxic drugs remains unknown.…”

Species differences in tumour responses to cancer chemotherapy

“…Despite efforts to investigate drug exposure in companion animals and the assumptions made to define the relationship between chemotherapy drug exposure and effect, conflicting results exist in the veterinary literature. In canine lymphoma, one study showed that dogs that developed grade III or IV neutropenia after chemotherapy demonstrated improved survival, leading to the suggestion that neutropenia was associated with more optimal drug exposure [104]. A separate study showed similar results: dogs requiring dose delays and dosage reductions during chemotherapy for lymphoma demonstrated improved outcomes compared with those without adjustments [105].…”