Avaliação do Potencial Cardiotóxico do Vp-16 Através de um Modelo Experimental Utilizando Ratas Albinas: Discussão de Achados Anátomo-Patológicos
DOI:
https://doi.org/10.32635/2176-9745.RBC.1985v31n2.3323Keywords:
Vp-16, CardiotoxicityAbstract
Based on anedoctal reports from the literature suggesting cardiotoxicity due to VP-16, the authors studied the effects on an eight-weekiy intraperitoneal (IP) injection of VP-16 in a group of fifty Albine rats, compared to Controls receiving isotonic saline during the same period of time. Group A (VP-16) received 5mg/kg weight IP weekly for eight courses. Group B (isotonic saline) had the same volume in isotônic saUne IP. Animais from Group A were killed at two-weekly intervals, according to sub-groups G1, G2, G3, G4 and G5 (10 rats in each interval). Animals from Group B were sacrified at the end of experiment. Anatomopathological studies of myocardium from Group A failed to show significant differences between subgroups, in spite of increasing total dosis. When both groups were compared, there were no statystical differences between the animals from Group A and B (P less 0.05). The authors conclude that there is no significant cardiac damage during the VP-16 therapy, at least in experimental conditions. The case reports found in the literature suggesting the possibility of cardiac damage due to VP-16 are probably secondary to unrelated factors.
Downloads
References
Arnold, A. M. and Whitehouse, J. M. A.: Etoposide: a new anti-cancer agent. Lancet, 1981, 2, 912. DOI: https://doi.org/10.1016/S0140-6736(81)91401-X
Cainer, D. A., Kingston, D. G. I. and Rao, M. M.: High Performance liquid chomatography of podophyllotoxins and related ligands. J. natural Prod. 1981, 44, 34. DOI: https://doi.org/10.1021/np50013a006
Loike, J. D. and Horwitz, S. B.: Effect of VP-16-213 on the intracellular degradation of DNA in Helacells. Biochemistry. 1976, 15, 5443. DOI: https://doi.org/10.1021/bi00670a004
Grieder, A., Maurer, R. and Stahelin, H.: Effeét of an epipodophyllotoxin derivative (VP-16-213) on macrololecular synthesis and mitosis in mastocytoma cells in vitro. Cancer Res. 1974,34, 1788.
Fischer, R. T., DeVita, V. T. Jr., Hubbard, S. M., Longo, D. L., Wesley, R., Chabner, B, A. and Young, R. C.; Diffuse Agressive Lymphomas: Increased survival after sequences of ProMACE and MoPP chemotherapy. Annalsof Int. Medicine. 1983, 98: 304-309. DOI: https://doi.org/10.7326/0003-4819-98-3-304
Bunn, P. A. Jr., Ihde, D. C.: Small-cell bronchogenic carcinoma: A review of therapeutic results. In Livingston R. B. (ed): Lung Cancer: Advances in Research and Treatment vol. 1: 169-208. The Hagus, Martinus Nihjoff. 1981. DOI: https://doi.org/10.1007/978-94-009-8207-9_8
Williams, S. D. and Einhort, L. H.: VP-16-213 salvage therapy for refractory germinal neoplasms. Cancer. 1979 44- 1514-1516. DOI: https://doi.org/10.1002/1097-0142(197910)44:4<1514::AID-CNCR2820440450>3.0.CO;2-4
Macbeth, F. R.; VM-26: Phase I and II studies. Cancer Chemotherapy Pharmacology. 1982, 7, 87. DOI: https://doi.org/10.1007/BF00254527
Brunner, K. W., Sontag, R. W., Ryssel, H. J. and Cavalli, F.: Comparison of the biologicic activity of VP-16-213 given i.v. and orally in capsules or drink ampules. Cancer Treatm. Rep. 1976. 60, 1377.
Issel, B.: The podophyllotoxin derivatives VP-16 and VM-26. Cancer Chemother. Pharmacol. 1982. 7, 73. DOI: https://doi.org/10.1007/BF00254525
Van Echo, D. A., Wiernick, P. H. and Aisnes, J.: High-dose VP-16-213 (NSC-141540) for the treatment of patients with previously treated acute leukemia. Cancer Clin. Trials. 1980. 3, 325.
D'lncalci, M. and Garattini, S.: Podophyilin derivatives VP-16 and VM-26: In the Cancer Pharmacology Annual, Chabner, B. A. and Pinedo, H. M. (ed.); Excerpta Medica, Amsterdam, 6:
1983.
Aisner, J., Van Echo, D. A., Whitacre, M. and Wiernis, P. H.: A phase I trial of continuous infusion VP-16-213 (etoposide). Cancer Chemotherapy Pharmacology, 7, 157. 1982. DOI: https://doi.org/10.1007/BF00254539
Schechter, J. P., Jones, S. E. and Jackson, R. A.: Myocardial infarction in a 27 year-old woman: possible complication of treatment with VP-16-213 (NSC-141540), mediastinal irradiation, or both. Cancer Treatm. Rep. 1975, 59, 887.
Bonnadona, G. and Monfardini, S.: Cardiotoxicity of Daunorubicin. Lancet. 1969. 1; 837. DOI: https://doi.org/10.1016/S0140-6736(69)92093-5
IB.Chabner, B. A. and Myers, C. E.: Clinical Pharmacology of Cancer Chemotherapy. In Cancer: Principies and Practice of Oncology, DeVita, V. T. Jr., Hellman, S. and Rosenberg, S. A. (Ed.l, 9; 182. 1982.
Danichev, D., Slioussantchouk, V., Paintrand, M. et al.: Elétron microscopy studies of the hearth and light microscopic studies of golden hamsters with Adriamycin, Daunomycin, AD 32 and aclaconomycin. Cancer Treatment Reports. 1979, 63: 875-888.
Myers, C. E., Liss, R. H., Ifrim, I,, Grotizinger, K. and Young, R. C.; Adriamycin: The role of lipid peroxidation in Cardiac toxicity and tumor response. Science. 1977. 197, 165. DOI: https://doi.org/10.1126/science.877547
Salmon, S. E., Liu, R. M. and Casazza, A. M.: Evaluation of new anthracycline analogs with the human stem cell assy. Cancer Chemotherapy Pharmacology. 1981,6, 103. DOI: https://doi.org/10.1007/BF00262325
Crooke, S. T., Bradner, W. T.: Mitomycin C: A review. Cancer Treatment Review. 1978, 3: 121-139. DOI: https://doi.org/10.1016/S0305-7372(76)80019-9