Correlation of pretreatment drug induced apoptosis in ovarian cancer cells with patient survival and clinical response

Journal of Translational Medicine

Research

James Rutledge¹  Allan Hallquist²  Mathieu Perree²  Howard Homesley³  Matthew Burrell⁴  Audrey Garrett⁵  Manuel Penalver⁶  Emery Salom⁷  Michael Chernick⁸  Cary A Presant⁹ 

[1] Data Vision, Dayton, OH, USA;DiaTech Oncology, Montreal, Canada;East Carolina University Brody School of Medicine, Greenville, NC, USA;Wake Forest University School of Medicine, Winston-Salem, NC, USA;Northside Hospital of Atlanta, Atlanta, GA, USA;Sacred Heart Medical Center, Eugene, OR, USA;South Florida Gynecologic Oncology, Coral Gables, FL, USA;South Florida Gynecologic Oncology, Coral Gables, FL, USA;Palmetto General Hospital, 2001 W. 68th St, 33016, Hialeah, FL, USA;The Lankenau Institute of Medical Research, Wynnewood, PA, USA;Wilshire Oncology Medical Group – US Oncology, Los Angeles, CA, USA;

关键词: Ovarian Cancer;    Paclitaxel;    Gemcitabine;    Carboplatin;    Epithelial Ovarian Cancer;   

DOI  :  10.1186/1479-5876-10-162

 received in 2012-01-18, accepted in 2012-07-31,  发布年份 2012

来源: Springer

【 摘 要 】

BackgroundThis study was performed to determine if a chemotherapy-induced apoptosis assay (MiCK) could predict the best therapy for patients with ovarian cancer.MethodsA prospective, multi-institutional and blinded trial of the assay was conducted in 104 evaluable ovarian cancer patients treated with chemotherapy. The MiCK assay was performed prior to therapy, but treating physicians were not told of the results and selected treatment only on clinical criteria. Outcomes (response, time to relapse, and survival) were compared to the drug-induced apoptosis observed in the assay.ResultsOverall survival in primary therapy, chemotherapy naïve patients with Stage III or IV disease was longer if patients received a chemotherapy which was best in the MiCK assay, compared to shorter survival in patients who received a chemotherapy that was not the best. (p < 0.01, hazard ratio HR 0.23). Multivariate model risk ratio showed use of the best chemotherapy in the MiCK assay was the strongest predictor of overall survival (p < 0.01) in stage III or IV patients. Standard therapy with carboplatin plus paclitaxel (C + P) was not the best chemotherapy in the MiCK assay in 44% of patients. If patients received C + P and it was the best chemotherapy in the MiCK assay, they had longer survival than those patients receiving C + P when it was not the best chemotherapy in the assay (p = 0.03). Relapse-free interval in primary therapy patients was longer if patients received the best chemotherapy from the MiCK assay (p = 0.03, HR 0.52). Response rates (CR + PR) were higher if physicians used an active chemotherapy based on the MiCK assay (p = 0.03).ConclusionThe MiCK assay can predict the chemotherapy associated with better outcomes in ovarian cancer patients. This study quantifies outcome benefits on which a prospective randomized trial can be developed.

【 授权许可】

CC BY   
© Salom et al.; licensee BioMed Central Ltd. 2012