Martínez HRA, Ceballos LAA, Flores JJA, Cuervo SJ, Gómez AD

Language: Spanish
References: 21
Page: 11-15
PDF size: 73.68 Kb.

ABSTRACT

Background: Due to poor results in the treatment of acute myeloid leukemia alternative options have been investigated to have a better control the disease. Vinblastine (VB) is a drug currently rarely used in its treatment.
Objective: Describe the response to the administration of vinblastine in patients with AML in relapse / refractory status.
Material and methods: Retrospective study of patients with AML treated at the Hospital Universitario de Monterrey from 2003 to 2010 who received VB as second-line treatment. We described the reduction of blasts in peripheral blood after administration of VB up to 2 weeks.
Results: Of a total of 137 patients 13 received vinblastine. VB was used at a dose of 6 mg/m2. As monotherapy in 5 patients, and in combination with cytarabine, 6-mercaptopurine and etoposide. First dose of vinblastine: response was observed with a decrease in leukocytes and peripheral blood blasts in 6 (45%) patients during the first week of treatment, with a cumulative response at 2 weeks of 61%. Second dose of vinblastine: Response 6 (66%) patients in the 1st week, and cumulative response at 2 weeks of 77%. Third dose of vinblastine: Response 3 (60%) in the first week. Cytoreductive response of VB used as monotherapy was similar to that obtained in different combinations. No significant adverse effects were observed with administration of VB.
Conclusions: A rapid response was observed in the majority of the patients. Vinblastine induces cytoreduction and partial response in refractory or intensively treated AML patients.

REFERENCES

1. Deschler B, Lübbert M. Acute Myeloid Leukemia: epidemiology and oncology. Cancer 2006;107(9):2099-2107.

2. Harry P. Prognostic factors in elderly patients with AML and the implications for treatment. Hematology 2007;420-428.

3. Crespo E. Epidemiología de las leucemias agudas. Rev Hematol Mex 2010;11(Supl. 1):37-39.

4. Buitrón-Santiago N, Arteaga-Ortiz L, Rosas-López A, Aguayo A, López-Karpovitch X, Crespo-Solís E. Acute myeloid leukemia in adults: experience at the Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán from 2003 to 2008. Rev Invest Clin 2010; 62(2):100-108.

5. Fernandez HF, Sun Z, Yao X, Litzow MR, et al. Anthracycline dose intensification in acute myeloid leukemia. N Engl J Med 2009;361:1249-1259.

6. Lowenberg B, Ossenkoppele GJ, van Putten W, Schouten HC, et al. High-dose daunorubicin in older patients with acute myeloid leukemia. N Engl J Med 2009;361:1235-1248.

7. Rowe JM. Optimal induction and post-remission therapy for AML in first remission. Hematology 2009;396-405.

8. Feldman EJ, Lancet J, Kolitz JE, Ritchie E, et al. Phase I Study of a Liposomal Carrier (CPX-351) Containing a Synergistic, Fixed Molar Ratio of Cytarabine (Ara-C) and Daunorubicin (DNR) in Advanced Leukemias. Blood 2008;112 (Abstract no. 2984).

9. Zhu, et al. Novel agents and regimens for acute myeloid leukemia: 2009 ASH annual meeting highlights. Journal of Hematology & Oncology 2010;3:17.

10. García-Manero G, et al. Final Report of a Phase II Trial of Vorinostat with Idarubicin and Cytarabine for Patients with Newly Diagnosed Acute Myelogenous Leukemia or Myelodysplastic Syndrome. Blood (ASH Annual Meeting Abstracts) 2011;615(Abstract 763).

11. Owellen RJ, Hartke CA, Hains FO. Pharmacokinetics and Metabolism of Vinblastine in Humans. Cancer Research 1977;37:2597-2602.

12. Piccinini M, Tazartes O, Mezzatesta C, et al. Proteasomes are a target of the anti-tumour drug vinblastine. Biochem J 2001;356:835-841.

13. Vacca A, Lurlaro M, Ribatti D, et al. Antiangiogenesis is produced by nontoxic doses of Vinblastine. Blood 1999;94(12):4143-4155.

14. Salerni BL, Bates DJ, Albershardt TC, et al. Vinblastine induces acute, cell cycle phase–independent apoptosis in some leukemias and lymphomas and can induce acute apoptosis in others when Mcl-1 is suppressed. Mol Cancer Ther 9(4); 791-802.

15. Stadheim TA, Xiao H, Eastman A. Inhibition of extracellular signal-regulated kinase (erk) mediates cell cycle phase inde- pendent apoptosis in vinblastine-treated ML-1 cells 1. Cancer Research 2001;61:1533-1540.

16. Darcy JP, Bethany BL, Salerni CHH. Vinblastine sensitizes leukemia cells to cyclin-dependent kinase inhibitors, inducing acute cell cycle phase-independent apoptosis. Cancer Biology & Therapy 2011;12(4):314-325.

17. Geiser CF, Mitus JW. Acute monocytic leukemia in children and its response to vinblastine. Cancer Chemother Rep 1975;59(2 Pt 1):385-388.

18. Müller MR, Sauter C, Erni J, Martz G. Influence of a new relapse treatment for acute myeloid leukemia (AML) on in vitro granulopoiesis. Anticancer Resp 1983; 3(2):127-131.

19. Asou N, Suzushima H, Hamasaki N. “AB-Triple V” therapy of relapsed or refractory acute myelogenous leukemia. Rinsho Ketsueki. 1989;30(2):169-174.

20. Sauter C, Fehr J, Frick P, et al. Acute Myelogenous Leukemia: Successful Treatment of Relapse with Cytosine Arabinoside, VP 16-213, Vincristine and Vinblastine (A-Triple-V). Eur J Cancer Clin Oncol 1982;18(8):733-731.

21. Caron JM, Herwood M. Vinblastine, a chemotherapeutic drug, inhibits palmitoylation of tubulin in human leukemic lymphocytes. Chemotherapy 2007;53:51-58.