Does l-Asparaginase Influence Efficacy or Toxicity When Added to a Standard CHOP Protocol for Dogs with Lymphoma?

Abstract

The purpose of this study was to evaluate response rates, 1st remission duration (FRD), and toxicity in dogs with previously untreated lymphoma receiving an identical CHOP-based combination chemotherapy protocol with or without L-asparaginase (LASP). One hundred fifteen dogs with lymphoma were scheduled to receive an identical CHOP-based chemotherapy protocol that included L-ASP. However, because of manufacturer-imposed random rationing, 31 dogs did not receive L-ASP as scheduled. The 2 treatment groups were statistically similar with respect to signalment and presence of historical negative prognostic factors. No difference was observed in the median FRD whether dogs did or did not receive L-ASP (206 versus 217 days, respectively; P = .67). No difference was observed in the median overall survival times between dogs receiving or not receiving L-ASP (310 versus 308 days, respectively; P = .84). No statistical difference was observed with respect to overall response rate between dogs that did or did not receive L-ASP (89.3% versus 87.1%, respectively; P = .75). Complete response rates between the groups also were no different (83.3% and 77.4% for L-ASP and non-L-ASP groups, respectively; P = .59). Prevalence of toxicity (neutropenia, diarrhea, or vomiting) and treatment delays (P = .80) also were similar between groups. The results of this study suggest that exclusion of L-ASP in this multidrug protocol does not significantly impact outcome. Therefore, it may be more appropriate to reserve the use of L-ASP for treating relapse in dogs with lymphoma that have failed induction therapy.

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

“…However, 79% of the neutropenic episodes occurred after concurrent administration of vincristine and L-asparaginase or vincristine and cyclophosphamide. Considering that complete absence of subcutaneous L-asparaginase in a doxorubicin-based multi-agent protocol does not shorten remission duration, 26 myelotoxicity arising from vincristine, cyclophosphamide, or both, may be the key predictor of remission duration. Escalation of either the vincristine or cyclophosphamide dose may prove to be safe given that lymphoma protocols have been published that use these drugs at dosages higher than those used in this protocol.…”

“…5,6,22,23 Not surprisingly, this is also the single example of an animal cancer for which 3 drug classes (ie, vinca alkaloids, alkylating agents, anthracyclines) are known to have substantial activity as single agents. [24][25][26] In addition to using multiple drugs, the maximization of dose intensity (drug dose/m 2 /wk) has proven to be of importance for improving the efficacy of chemotherapy for some human cancers. 1,27,28 This is explained by Norton's model, which predicts that higher doses of chemotherapy will kill a higher fraction of tumor cells and that reducing the intertreatment interval will reduce intertreatment tumor repopulation.…”

Predictive value of p16 or Rb inactivation in a model of naturally occurring canine non-Hodgkin's lymphoma

“…4 We screened the PPARbstimulating activity of prostaglandins, hydroxy-eicosatetraenoic acids (HETEs), the hormones of the adrenal cortex, derivatives of cholesterol and flavonoids. Among the compounds we examined, interestingly, the hormones of the adrenal cortex, dehydroepiandrosterone sulfate DHEA-S and hydrocortisone (dexamethasone (Dex)), showed the strong PPARb-stimulating activity (Figure 2a), and one of the flavonoids from Scutellaria radix, baicalein, 5 also showed strong PPARb-stimulating activity (Figure 2b).…”

“…1 With standard of care, remission can be achieved in 485% of canine NHL cases, and median survival ranges between 9 and 12 months. 4,5 This represents approximately 10% of an average canine lifetime, thus providing a fair target to compare the outcome between dogs and people. Predictive factors for survival in dogs include immunophenotype, clinical substage and histologic subtype.…”

Comparison of 3 Protocols for Treatment after Induction of Remission in Dogs with Lymphoma

“…Despite initial high CR rates, subsequent relapses are commonly observed; published median first-remission durations have ranged from 140 to 385 days. [1][2][3][4][5][6][7][8][9] For patients in CR, various treatment strategies have been explored to eliminate minimal residual disease that could contribute to relapse. Such strategies included highdose chemotherapy with 10 or without 11 autologous bone marrow transplantation, standard-dose maintenance therapy, [1][2][3][4]6,9,12 chemoimmunotherapy, 13 half-body radiation therapy (HBRT), [14][15][16] or consolidation with new drug combinations.…”