2015 Antineoplastics

CELL KILL HYPOTHESIS

The CELL KILL HYPOTHESIS proposes that actions of CCS drugs follow first order kinetics:  a given dose kills a constant PROPORTION of a tumor cell population (rather than a constant NUMBER of cells).

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The example shows the effects of tumour burden, scheduling, dosing, and initiation/duration of treatment on patient survival.

Log Kill Diagram

Modified from Katzung Basic and Clinical Pharmacology

 

The tumour burden in an untreated patient would progress along the path described by the RED LINE - the tumour is detected (using conventional techniques) when the tumour burden reaches 109 cells; the patient is symptomatic at 1010-1011 cells, and dies at 1012 cells.
3 treatment options are shown:
  • DARK BLUE LINE: Infrequent scheduling of treatment courses with low (1 log kill) dosing and a late start prolongs survival but does not cure the patient (i.e., kill rate < growth rate)

  • LIGHT BLUE LINE: More intensive and frequent treatment, with adequate (2 log kill) dosing and an earlier start is successful (i.e., kill rate > growth rate)

  • GREEN LINE: Early surgical removal of the primary tumour decreases the tumour burden. Chemotherapy will remove persistant secondary tumours, and the total duration of therapy does not have to be as long as when chemotherapy alone is used.

  1. early start to the treatment is (obviously!) helpful

  2. treatment must continue past the time when cancer cells can't be detected using conventional techniques

  3. appropriate scheduling of treatment courses and care to ensure that a sufficient log-kill is obtained are also crucial factors that enable success
Email: Dr. Janet Fitzakerley | ©2015 University of Minnesota Medical School Duluth | Last modified: 6-may-15 6:36 AM