Tumor growth rates derived from data for patients in a clinical trial correlate strongly with patient survival: a novel strategy for evaluation of clinical trial data.
OBJECTIVE
The slow progress in developing new cancer therapies can be attributed in part to the long time spent in clinical development. To hasten development, new paradigms especially applicable to patients with metastatic disease are needed.


METHODS
We present a new method to predict survival using tumor measurement data gathered while a patient with cancer is receiving therapy in a clinical trial. We developed a two-phase equation to estimate the concomitant rates of tumor regression (regression rate constant d) and tumor growth (growth rate constant g).


RESULTS
We evaluated the model against serial levels of prostate-specific antigen (PSA) in 112 patients undergoing treatment for prostate cancer. Survival was strongly correlated with the log of the growth rate constant, log(g) (Pearson r = -0.72) but not with the log of the regression rate constants, log(d) (r = -0.218). Values of log(g) exhibited a bimodal distribution. Patients with log(g) values above the median had a mortality hazard of 5.14 (95% confidence interval, 3.10-8.52) when compared with those with log(g) values below the median. Mathematically, the minimum PSA value (nadir) and the time to this minimum are determined by the kinetic parameters d and g, and can be viewed as surrogates.


CONCLUSIONS
This mathematical model has applications to many tumor types and may aid in evaluating patient outcomes. Modeling tumor progression using data gathered while patients are on study, may help evaluate the ability of therapies to prolong survival and assist in drug development.
Stein
Wilfred D
WD
Medical Oncology Branch, National Cancer Institute, Center for Cancer Research, National Institutes of Health, Bethesda, Maryland 20892, USA.
Figg
William Doug
WD
Dahut
William
W
Stein
Aryeh D
AD
Hoshen
Moshe B
MB
Price
Doug
D
Bates
Susan E
SE
Fojo
Tito
T
D048708:Cell Growth Processes / Q000502:physiology; D002986:Clinical Trials as Topic / Q000379:methods*; D003627:Data Interpretation, Statistical; D023381:Endpoint Determination; D006801:Humans; D008297:Male; D008954:Models, Biological; D017430:Prostate-Specific Antigen / Q000378:metabolism*; D011471:Prostatic Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology*; D015203:Reproducibility of Results; D016896:Treatment Outcome
D017430:Prostate-Specific Antigen