scholarly journals Circulating tumor cell telomerase activity as a prognostic marker for overall survival in SWOG 0421: A phase III metastatic castration resistant prostate cancer trial

2014 ◽  
Vol 136 (8) ◽  
pp. 1856-1862 ◽  
Author(s):  
Amir Goldkorn ◽  
Benjamin Ely ◽  
Catherine M. Tangen ◽  
Yu-Chong Tai ◽  
Tong Xu ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Overall Survival ◽  
Tumor Cell ◽  
Prognostic Marker ◽  
Circulating Tumor Cell ◽  
Telomerase Activity ◽  
Phase Iii ◽  
Castration Resistant Prostate Cancer ◽  
Cancer Trial ◽  
Castration Resistant

scholarly journals Circulating Tumor Cell Counts Are Prognostic of Overall Survival in SWOG S0421: A Phase III Trial of Docetaxel With or Without Atrasentan for Metastatic Castration-Resistant Prostate Cancer

2014 ◽  
Vol 32 (11) ◽  
pp. 1136-1142 ◽  
Author(s):  
Amir Goldkorn ◽  
Benjamin Ely ◽  
David I. Quinn ◽  
Catherine M. Tangen ◽  
Louis M. Fink ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Overall Survival ◽  
Tumor Cell ◽  
Roc Curves ◽  
Circulating Tumor Cell ◽  
Phase Iii ◽  
Castration Resistant Prostate Cancer ◽  
Phase Iii Trial ◽  
Castration Resistant ◽  
Baseline Psa

Purpose Circulating tumor cell (CTC) enumeration has not been prospectively validated in standard first-line docetaxel treatment for metastatic castration-resistant prostate cancer. We assessed the prognostic value of CTCs for overall survival (OS) and disease response in S0421, a phase III trial of docetaxel plus prednisone with or without atrasentan. Patients and Methods CTCs were enumerated at baseline (day 0) and before cycle two (day 21) using CellSearch. Baseline counts and changes in counts from day 0 to 21 were evaluated for association with OS, prostate-specific antigen (PSA), and RECIST response using Cox regression as well as receiver operator characteristic (ROC) curves, integrated discrimination improvement (IDI) analysis, and regression trees. Results Median day-0 CTC count was five cells per 7.5 mL, and CTCs < versus ≥ five per 7.5 mL were significantly associated with baseline PSA, bone pain, liver disease, hemoglobin, alkaline phosphatase, and subsequent PSA and RECIST response. Median OS was 26 months for < five versus 13 months for ≥ five CTCs per 7.5 mL at day 0 (hazard ratio [HR], 2.74 [adjusting for covariates]). ROC curves had higher areas under the curve for day-0 CTCs than for PSA, and IDI analysis showed that adding day-0 CTCs to baseline PSA and other covariates increased predictive accuracy for survival by 8% to 10%. Regression trees yielded new prognostic subgroups, and rising CTC count from day 0 to 21 was associated with shorter OS (HR, 2.55). Conclusion These data validate the prognostic utility of CTC enumeration in a large docetaxel-based prospective cohort. Baseline CTC counts were prognostic, and rising CTCs at 3 weeks heralded significantly worse OS, potentially serving as an early metric to help redirect and optimize therapy in this clinical setting.

scholarly journals Circulating Tumor Cell Number as a Response Measure of Prolonged Survival for Metastatic Castration-Resistant Prostate Cancer: A Comparison With Prostate-Specific Antigen Across Five Randomized Phase III Clinical Trials

2018 ◽  
Vol 36 (6) ◽  
pp. 572-580 ◽  
Author(s):  
Glenn Heller ◽  
Robert McCormack ◽  
Thian Kheoh ◽  
Arturo Molina ◽  
Matthew R. Smith ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Overall Survival ◽  
Specific Antigen ◽  
Circulating Tumor Cell ◽  
Phase Iii ◽  
Response Measure ◽  
Castration Resistant Prostate Cancer ◽  
End Points ◽  
End Point ◽  
Castration Resistant

Purpose Measures of response that are clinically meaningful and occur early are an unmet need in metastatic castration-resistant prostate cancer clinical research and practice. We explored, using individual patient data, week 13 circulating tumor cell (CTC) and prostate-specific antigen (PSA) response end points in five prospective randomized phase III trials that enrolled a total of 6,081 patients—COU-AA-301, AFFIRM, ELM-PC-5, ELM-PC-4, and COMET-1— ClinicalTrials.Gov identifiers: NCT00638690, NCT00974311, NCT01193257, NCT01193244, and NCT01605227, respectively. Methods Eight response end points were explored. CTC nonzero at baseline and 0 at 13 weeks (CTC0); CTC conversion (≥ 5 CTCs at baseline, ≤ 4 at 13 weeks—the US Food and Drug Administration cleared response measure); a 30%, 50%, and 70% decrease in CTC count; and a 30%, 50%, and 70% decrease in PSA level. Patients missing week-13 values were considered nonresponders. The discriminatory strength of each end point with respect to overall survival in each trial was assessed using the weighted c-index. Results Of the eight response end points, CTC0 and CTC conversion had the highest weighted c-indices, with smaller standard deviations. For CTC0, the mean (standard deviation) was 0.81 (0.04); for CTC conversion, 0.79 (0.03); for 30% decrease in CTC count, 0.72 (0.06); for 50% decrease in CTC count, 0.72 (0.06); for 70% decrease in CTC count, 0.73 (0.05); for 30% decrease in PSA level, 0.71 (0.03); for 50% decrease in PSA level, 0.72 (0.06); and for 70% decrease in PSA level, 0.74 (0.05). Seventy-five percent of eligible patients could be evaluated with the CTC0 end point, compared with 51% with the CTC conversion end point. Conclusion The CTC0 and CTC conversion end points had the highest discriminatory power for overall survival. Both are robust and meaningful response end points for early-phase metastatic castration-resistant prostate cancer clinical trials. CTC0 is applicable to a significantly higher percentage of patients than CTC conversion.

scholarly journals Circulating Tumor Cell Analysis in Patients with Progressive Castration-Resistant Prostate Cancer

2007 ◽  
Vol 13 (7) ◽  
pp. 2023-2029 ◽  
Author(s):  
David R. Shaffer ◽  
Margaret A. Leversha ◽  
Daniel C. Danila ◽  
Oscar Lin ◽  
Rita Gonzalez-Espinoza ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Tumor Cell ◽  
Circulating Tumor Cell ◽  
Cell Analysis ◽  
Castration Resistant Prostate Cancer ◽  
Castration Resistant

scholarly journals Overall Survival of Black and White Men With Metastatic Castration-Resistant Prostate Cancer Treated With Docetaxel

2019 ◽  
Vol 37 (5) ◽  
pp. 403-410 ◽  
Author(s):  
Susan Halabi ◽  
Sandipan Dutta ◽  
Catherine M. Tangen ◽  
Mark Rosenthal ◽  
Daniel P. Petrylak ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Overall Survival ◽  
Black Men ◽  
Performance Status ◽  
Specific Antigen ◽  
White Men ◽  
Phase Iii ◽  
Castration Resistant Prostate Cancer ◽  
Black And White ◽  
Castration Resistant

Purpose Several studies have reported that among patients with localized prostate cancer, black men have a shorter overall survival (OS) time than white men, but few data exist for men with advanced prostate cancer. The primary goal of this analysis was to compare the OS in black and white men with metastatic castration-resistant prostate cancer (mCRPC) who were treated in phase III clinical trials with docetaxel plus prednisone (DP) or a DP-containing regimen. Methods Individual participant data from 8,820 men with mCRPC randomly assigned in nine phase III trials to DP or a DP-containing regimen were combined. Race was based on self-report. The primary end point was OS. The Cox proportional hazards regression model was used to assess the prognostic importance of race (black v white) adjusted for established risk factors common across the trials (age, prostate-specific antigen, performance status, alkaline phosphatase, hemoglobin, and sites of metastases). Results Of 8,820 men, 7,528 (85%) were white, 500 (6%) were black, 424 (5%) were Asian, and 368 (4%) were of unknown race. Black men were younger and had worse performance status, higher testosterone and prostate-specific antigen, and lower hemoglobin than white men. Despite these differences, the median OS was 21.0 months (95% CI, 19.4 to 22.5 months) versus 21.2 months (95% CI, 20.8 to 21.7 months) in black and white men, respectively. The pooled multivariable hazard ratio of 0.81 (95% CI, 0.72 to 0.91) demonstrates that overall, black men have a statistically significant decreased risk of death compared with white men ( P < .001). Conclusion When adjusted for known prognostic factors, we observed a statistically significant increased OS in black versus white men with mCRPC who were enrolled in these clinical trials. The mechanism for these differences is not known.

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