The Use Of Lithium In The Prophylaxis And Treatment Of Chemotherapy Induced Neutropenia (CIN): A Cost-Effective Option Or Hazard
| Authors | |
|---|---|
| Year of publication | 2006 |
| Type | Article in Periodical |
| Magazine / Source | Support Care Cancer |
| MU Faculty or unit | |
| Citation | |
| Field | Oncology and hematology |
| Keywords | litihum;akt kinase;chemotherapy;chemoresistance;neutropenia; |
| Description | Introduction: Lithium is an antimanic agent successfully used in the treatment of patients with bipolar disorder. Even at therapeutic levels many patients experience one of the most frequent non-toxic and reversible side effect of lithium: leukocytosis. Due this effect, lithium has been used in the treatment and prophylaxis of CIN before the availability of colony-stimulating factors (CSF) and it remains as a costeffective option compared with CSF. Recently, lithium has been reported to protect cells against apoptosis via a direct inhibition of GSK-3beta and activation of Akt/PKB. Both kinases play important role in processes of primary and inducible tumor chemoresistance. Results: I. 151 MTT tests were performed for in-vitro testing of chemo-sensitivity of 53 primary tumours against cisplatin, melphalan, doxorubicin and paclitaxel with or without presence of 10mM or 2mM lithium. At the concentration of 10mM, lithium enormously increased chemoresistance of primary tumours against doxorubicin (p=0,000000453) and paclitaxel (p=0,000277692). At the concentration of 2mM the lithium significantly increases chemoresistance only against doxorubicin. There was no effect of lithium on alkylating agents. II. A retrospective analysis of clinical data of 271 patients who developed CIN and were treated by lithium carbonate (1st group) or without any treatment (2nd group) was done. Median of neutrophils counts at the initial blood counts examinations after chemotherapy was 0,9 and 0.94x109/L (1st and 2nd group respectively) and after 7 days of lithium administration was 2,71x109/L compared to 2,03x109/L at the 2nd group (p=0,15). Conclusions: This study demonstrates: I) lithium can increase chemoresistance of primary tumours against cytostatic agents and II) the effect of lithium on the neutrophils counts is disputative. Therefore there is no rationalization for the use of lithium in the treatment and prophylaxis of CIN. Acknowledgements: The work was supported by grants from The Czech T.Fox Run 2005 and IGA MZCR NR/8335-3. |