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. 2012 Aug 8:10:162.
doi: 10.1186/1479-5876-10-162.

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

Emery Salom  1 , Manuel Penalver, Howard Homesley, Matthew Burrell, Audrey Garrett, Cary A Presant, James Rutledge, Michael Chernick, Allan Hallquist, Mathieu Perree
Affiliations

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

Emery Salom et al. J Transl Med. .

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).

Conclusion: 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.

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Figures

Figure 1
Figure 1
Overall survival of patients with stage 3 or 4 primary disease without prior chemotherapy. Red line, 44 patients receiving a best chemotherapy. Blue line, 29 patients receiving non-best chemotherapy. P < 0.01.
Figure 2
Figure 2
Recurrence-free interval of patients with stage 3 or 4 primary disease without prior chemotherapy. Red line, 43 patients receiving a best chemotherapy. Blue line, 29 patients receiving non-best chemotherapy. P = 0.03.
See this image and copyright information in PMC

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