METRONOMIC DELIVERY

 

An example of a typical treatment regimen calls for a twice-weekly schedule for 3-4 weeks, followed by a reduction in frequency over a total period of 3-6 months. An alternative treatment based on metronomic delivery infuses numerous small doses over time. This strategy attempts to minimize the peak chemo toxicity level while increasing the duration over which drug levels are therapeutic. This concept is illustrated in the simulation data below.

 

 

Metronomic Delivery 
A recent study shows that continuous intrathecal treatment with methotrexate via subcutaneous port improved the therapeutic effect and reduced the complications associated with treatment of cancer. The frequent small drug doses over a short period were shown to reduce the incidence of complications by enabling long term CSF exposure to cytotoxic drug concentrations while avoiding excessively high and potentially neurotoxic drug concentrations. We hypothesize that patient survival time can be increased by a personalized metronomic delivery system, which could result in a sustained higher chemotherapy concentration (greater therapeutic effect) yet achieve a lower peak drug concentration (less toxicity) at various parts of the brain.

 

SUPPORTING LITERATURE

  • Continuous low-dose anti-angiogenic/metronomic chemotherapy: from the research laboratory into the oncology clinic, R. S. Kerbel, G. Klement, K. I. Pritchard & B. Kamen, Annals of Oncology 13: 12-15, 2002Available here.

     

  • “Concentration x time” methotrexate via subcutaneous reservoir: a less toxic regimen for intraventricular chemotherapy of central nervous system neoplasms. Bleyer WA, Poplack DG, Simon RM. Blood 1978;51(5):835-842Available here.

     

  • Metronomic low-dose oral cyclophosphamide and methotrexate plus or minus thalidomide in metastatic breast cancer: antitumor activity and biological effects, M. Colleoni, L. Orlando, G. Sanna, A. Rocca, P. Maisonneuve, G. Peruzzotti, R. Ghisini, M. T. Sandri, L. Zorzino, F. Nole, G. Viale & A. Goldhirsch, Annals of Oncology 17: 232–238, 2006Available here.

     

  • Less is more, regularly: metronomic dosing of cytotoxic drugs can target tumor angiogenesis in mice, Douglas Hanahan, Gabriele Bergers, Emily Bergsland, Journal of Clinical Investigation 2000; vol 105, issue 8:1045–1047Available here.
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