title: Other paradigms: growth rate constants and tumor burden determined using computed tomography data correlate strongly with the overall survival of patients with renal cell carcinoma.
abstract: 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.
authors.affiliation: Medical Oncology Branch, National Cancer Institute, NIH, Bethesda, MD20892, USA.
authors.forename: Wilfred D
authors.initials: WD
authors.lastname: Stein
authors.forename: Hui
authors.initials: H
authors.lastname: Huang
authors.forename: Michael
authors.initials: M
authors.lastname: Menefee
authors.forename: Maureen
authors.initials: M
authors.lastname: Edgerly
authors.forename: Herb
authors.initials: H
authors.lastname: Kotz
authors.forename: Andrew
authors.initials: A
authors.lastname: Dwyer
authors.forename: James
authors.initials: J
authors.lastname: Yang
authors.forename: Susan E
authors.initials: SE
authors.lastname: Bates
mesh_terms: D000970:Antineoplastic Agents / Q000627:therapeutic use; D002292:Carcinoma, Renal Cell / Q000000981:diagnostic imaging / Q000188:drug therapy / Q000473:pathology*; D017322:Clinical Trials, Phase II as Topic; D018450:Disease Progression; D034261:Epothilones / Q000627:therapeutic use; D006801:Humans; D007680:Kidney Neoplasms / Q000000981:diagnostic imaging / Q000188:drug therapy / Q000473:pathology*; D009362:Neoplasm Metastasis / Q000188:drug therapy / Q000473:pathology; D011379:Prognosis; D012044:Regression Analysis; D016019:Survival Analysis; D014057:Tomography, X-Ray Computed; D016896:Treatment Outcome
chemical_list: D000970:Antineoplastic Agents; D034261:Epothilones; C430592:ixabepilone; C093788:epothilone B