Fractional kill

In oncology, the fact that one round of chemotherapy does not kill all the cells in a tumor is a poorly understood phenomenon called fractional kill, or fractional cell kill.

The fractional kill hypothesis states that a defined chemotherapy concentration, applied for a defined time period, will kill a constant fraction of the cells in a population, independent of the absolute number of cells.[1][2][3] In solid tumors, poor access of the tumor to the drug can limit the fraction of tumor cells killed, but the validity of the fractional kill hypothesis has also been established in animal models of leukemia, as well as in human leukemia and lymphoma, where drug access is less of an issue.[3]

Because only a fraction of the cells die with each treatment, repeated doses must be administered to continue to reduce the size of the tumor.[4] Current chemotherapy regimens apply drug treatment in cycles, with the frequency and duration of treatments limited by toxicity to the patient.[3] The goal is to reduce the tumor population to zero with successive fractional kills.[3] For example, assuming a 99% kill per cycle of chemotherapy, a tumor of 1011 cells would be reduced to less than one cell with six treatment cycles: 1011 * 0.016 < 1.[3] However, the tumor can also re-grow during the intervals between treatments, limiting the net reduction of each fractional kill.[4]

  1. ^ Berenbaum, M. C. (1972). "In vivo determination of the fractional kill of human tumor cells by chemotherapeutic agents." Cancer Chemother Rep 56(5): 563-71.
  2. ^ Skipper, H. E. (1979). "Historic milestones in cancer biology: a few that are important in cancer treatment (revisited)." Semin Oncol 6(4): 506-14.
  3. ^ a b c d e Chabner, B. and D. L. Longo (2006). Cancer Chemotherapy and Biotherapy: Principles and Practice. Philadelphia, Lippincott Willians & Wilkins.
  4. ^ a b Skeel, R. T. (2003). Handbook of Cancer Chemotherapy, Lippincott Williams & Wilkins.