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Lisofylline as an adjuvant to high dose cytotoxic therapy
International Journal of Oncology
|April 30, 2011
Summary
Lisofylline, a cancer therapy adjunct, accelerates white blood cell recovery and enhances tumor cell killing. This dimethylxanthine derivative improves outcomes when combined with chemotherapy or radiation.
Area of Science:
- Pharmacology
- Oncology
- Hematology
Background:
- Cytotoxic anticancer therapies induce hematopoietic growth inhibitors, impairing white blood cell recovery.
- Lisofylline, a dimethylxanthine derivative, has shown potential in mitigating these effects.
Purpose of the Study:
- To evaluate lisofylline's efficacy in enhancing leukocyte recovery following high-dose chemotherapy or total body radiation in a murine cancer model.
- To assess lisofylline's impact on tumor cell killing and response to cytotoxic agents in EMT-6 mammary carcinoma.
Main Methods:
- Mice with EMT-6 mammary carcinoma were treated with high-dose chemotherapy (cyclophosphamide, melphalan, BCNU, 5-fluorouracil) or total body radiation.
- The effects of lisofylline and/or granulocyte-colony stimulating factor (G-CSF) on leukocyte recovery and animal weight were examined.
- Impact on bone marrow colony-forming unit-granulocyte-macrophage (CFU-GM) and tumor cell killing was assessed.
Main Results:
- Lisofylline effectively accelerated white blood cell and granulocyte recovery, comparable to G-CSF.
- Lisofylline provided protection against weight loss induced by melphalan but not other cytotoxic agents.
- Lisofylline enhanced the killing of EMT-6 tumor cells and significantly increased tumor growth delay when combined with cytotoxic therapies.
Conclusions:
- Lisofylline selectively enhances hematopoietic recovery in mice undergoing high-dose chemotherapy or radiation.
- Lisofylline potentiates the anti-tumor effects of several cytotoxic agents, suggesting a role as an adjunct therapy.
- Further investigation into lisofylline's therapeutic potential in cancer treatment is warranted.
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