TY - JOUR
T1 - Other paradigms
T2 - Growth rate constants and tumor burden determined using computed tomography data correlate strongly with the overall survival of patients with renal cell carcinoma
AU - Stein, Wilfred D.
AU - Huang, Hui
AU - Menefee, Michael
AU - Edgerly, Maureen
AU - Kotz, Herb
AU - Dwyer, Andrew
AU - Yang, James
AU - Bates, Susan E.
PY - 2009/9
Y1 - 2009/9
N2 - In solid tumors, where curative therapies still elude oncologists, novel paradigms are needed to assess the efficacy of new therapies and those already approved. We used radiologic measurements obtained in patients with metastatic renal cell carcinoma enrolled in a phase II study of the epothilone B analog, ixabepilone (Ixempra), to address this issue. Using a novel 2-phase mathematical equation, we used the radiologic measurements to estimate the concomitant rates of tumor regression and growth (regression and growth rate constants). Eighty-one patients were enrolled on the ixabepilone trial at the time of this analysis. Growth rate constants were determined using computed tomography measurements obtained exclusively while a patient was enrolled on study. The growth rate constants of renal cell carcinomas treated with ixabepilone were significantly reduced compared with those of tumors in patients who received placebo in a previous trial. Furthermore, a correlation with overall survival was found for both the growth rate constant and the initial tumor burden; and this correlation was even stronger when both the growth rate constant and the initial tumor burden were combined. The readily amenable mathematical model described herein has potential applications to many tumor types that can be assessed with imaging modalities. Because the growth rate constant seems to be a surrogate for survival, assessment could aid in the evaluation of relative efficacies of different therapies and perhaps in assessing the potential individual benefit of an experimental therapy.
AB - In solid tumors, where curative therapies still elude oncologists, novel paradigms are needed to assess the efficacy of new therapies and those already approved. We used radiologic measurements obtained in patients with metastatic renal cell carcinoma enrolled in a phase II study of the epothilone B analog, ixabepilone (Ixempra), to address this issue. Using a novel 2-phase mathematical equation, we used the radiologic measurements to estimate the concomitant rates of tumor regression and growth (regression and growth rate constants). Eighty-one patients were enrolled on the ixabepilone trial at the time of this analysis. Growth rate constants were determined using computed tomography measurements obtained exclusively while a patient was enrolled on study. The growth rate constants of renal cell carcinomas treated with ixabepilone were significantly reduced compared with those of tumors in patients who received placebo in a previous trial. Furthermore, a correlation with overall survival was found for both the growth rate constant and the initial tumor burden; and this correlation was even stronger when both the growth rate constant and the initial tumor burden were combined. The readily amenable mathematical model described herein has potential applications to many tumor types that can be assessed with imaging modalities. Because the growth rate constant seems to be a surrogate for survival, assessment could aid in the evaluation of relative efficacies of different therapies and perhaps in assessing the potential individual benefit of an experimental therapy.
KW - Cancer clinical trials
KW - Chemotherapy assessment
KW - Chemotherapy efficacy
KW - Chemotherapy evaluation
KW - Phase II studies
KW - RECIST
UR - http://www.scopus.com/inward/record.url?scp=70350139039&partnerID=8YFLogxK
U2 - 10.1097/PPO.0b013e3181be1b90
DO - 10.1097/PPO.0b013e3181be1b90
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C2 - 19826366
AN - SCOPUS:70350139039
SN - 1528-9117
VL - 15
SP - 441
EP - 447
JO - Cancer Journal (United States)
JF - Cancer Journal (United States)
IS - 5
ER -