Tumor Growth and Regression Rate Constants - One Value, Many Applications
*Tito Fojo, NIH 


Unfortunately progress in treating metastatic tumors continues to be incremental with gains recorded as marginal extensions in survival endpoints, and cures rarely achieved. In advanced disease, we have previously shown that the effect of a therapy is a result of simultaneous effects on the rate constants of tumor regression and growth. Where sufficient data is available we can also estimate and consider the fraction of tumor killed by the drug. Thus we describe therapies in terms of their effects on the growth (g) and regression (d) rate constants of tumors and the fraction of cells killed (Ø). For any trial the data can be presented as growth curves that are a consequence of the median values of g, d, and Ø parameters and establish whether gains, if any, observed with a therapy have occurred because of effects on g, d or Ø, or on some combination. Our analyses show that most cancer therapies developed in the metastatic setting are g therapies that reduce the growth rate constant and prolong survival without increasing fractional cell kill. This outcome is no doubt a consequence of trial designs that are designed to prolong survival by a few months. Such g therapies might even result in a higher ORR, not because of greater cell kill but as a consequence of its ability to delay the growth of the remaining “relatively resistant” tumor fraction. Understanding this has provided us insight into how our therapies work, why our therapeutic advances continue to be marginal and why time and again adjuvant and neo-adjuvant trials fail to provide benefit. We now also have better understanding of the nature of drug resistance.