Evaluation of a Lipidic Microemulsion Associated to Carmustine (BCNU) in Combined Chemotherapy Protocol for Malignant Lymphoma Treatment in Dogs
*Sílvia Regina Ricci Lucas, Diana Helena de Benedetto Pozzi, Raul Cavalcante Maranhão, José Luiz Guerra, Bruna Maria Pereira Coelho
*Faculdade de Medicina Veterinária e Zootecnia da Universidade de São Paulo, Av. Prof. Dr. Orlando Marques de Paiva
São Paulo, BR
Malignant lymphoma can affect several species like human beings and dogs and are sensible to chemotherapy. However, in dogs as well as in human beings, the toxicity associated with the current chemotherapeutic protocols still is a limiting factor. Several strategies have been developed to deliver drugs directly to the tumoral cells. After the finding that some type of tumoral cells over-express low density lipoprotein (LDL) receptors, some investigators studied the possibility of binding an artificial lipidic microemulsion (LDE) similar to LDL, to lipophilic drugs, to attempt a decrease in chemotherapy associated toxicity. The purpose of the present study was to evaluate clinical, hematological and biochemical parameters of dogs treated with a combined chemotherapy protocol using one of the chemotherapy agent incorporated to LDE.
Thirteen dogs with malignant multicentric lymphoma, stage III to V, according WHO, were studied. In the control group, the dogs were treated with BCNU (50mg/m2 at 6 weeks intervals), vincristine (0,75mg/m2 at 3 weeks intervals) and prednisone (40mg/m2 each other day). In the LDE group they received the complex BCNU/LDE, vincristine and prednisone. The micro-emulsion was prepared from a lipid mixtures, sonicated and purified according the procedures described by Ginsburg et al, 1982, modified by Maranhão et al, 1994. CBC, RBC and platelets count were performed a week after each cycle of chemotherapy. Biochemical profiles were performed once a month. The WBC, neutrophils and platelets were compared between the groups by Mann Whitney Test.
Histopathologic grade and immunophenotyping of tumors were available for all dogs. Only one low-grade tumor was detected in the LDE group. There were 4 high and 8 intermediate-grade tumors. Twelve T cell and only one B cell tumor was detected. Hypercalcemia was observed in one dog from each group. The prognostic factors were observed in both groups and they were considered similar after data analysis. Cumulative doses of BCNU in the control group ranged from 100 to 298 mg/m2. In the LDE group, cumulative doses of BCNU/LDE ranged from 150 to 405 mg/m2. Six dogs from the control group (87,5%) and four from LDE group (66,7%) achieved complete remission after induction phase. In general, neutropenia was equally intense for both groups (p>.05). There was no difference in survival rates, platelet counts, RBC or biochemical profiles between the groups.
The aim of the LDE utilization is to reduce chemotherapy toxicity because this drug should be selectively taken up by malignant cells with up regulation of the LDL receptors.
Considering LDE utilization for this population, no significant differences between groups were found. Like all treated animals were in an advanced stage of the disease, it is possible that the tumor growth rate is low at this time, consequently the number of over-expressed rLDL may be reduced. This aspect may justify the findings of no difference between the groups. More studies should be conduced in order to evaluate LDE uptake by canine tumoral cells.