title: Correlation of pretreatment drug induced apoptosis in ovarian cancer cells with patient survival and clinical response.
abstract: BACKGROUND
  This study was performed to determine if a chemotherapy-induced apoptosis assay (MiCK) could predict the best therapy for patients with ovarian cancer.
  
  
  METHODS
  A 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.
  
  
  RESULTS
  Overall 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).
  
  
  CONCLUSIONS
  The 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.
authors.affiliation: South Florida Gynecologic Oncology, Coral Gables, FL, USA. bestchemo@gmail.com
authors.forename: Emery
authors.initials: E
authors.lastname: Salom
authors.forename: Manuel
authors.initials: M
authors.lastname: Penalver
authors.forename: Howard
authors.initials: H
authors.lastname: Homesley
authors.forename: Matthew
authors.initials: M
authors.lastname: Burrell
authors.forename: Audrey
authors.initials: A
authors.lastname: Garrett
authors.forename: Cary A
authors.initials: CA
authors.lastname: Presant
authors.forename: James
authors.initials: J
authors.lastname: Rutledge
authors.forename: Michael
authors.initials: M
authors.lastname: Chernick
authors.forename: Allan
authors.initials: A
authors.lastname: Hallquist
authors.forename: Mathieu
authors.initials: M
authors.lastname: Perree
mesh_terms: D000971:Antineoplastic Combined Chemotherapy Protocols / Q000494:pharmacology / Q000627:therapeutic use*; D017209:Apoptosis / Q000187:drug effects*; D005260:Female; D006801:Humans; D010051:Ovarian Neoplasms / Q000188:drug therapy* / Q000473:pathology; D015996:Survival Rate; D016896:Treatment Outcome