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Biomarker analysis of the MITO2 phase III trial of first-line treatment in ovarian cancer: predictive value of DNA-PK and phosphorylated ACC

BACKGROUND: No biomarker is available to predict prognosis of patients with advanced ovarian cancer (AOC) and guide the choice of chemotherapy. We performed a prospective-retrospective biomarker study within the MITO2 trial on the treatment of AOC. Patients and methods: MITO2 is a randomised multice...

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Autores principales: Perrone, Francesco, Baldassarre, Gustavo, Indraccolo, Stefano, Signoriello, Simona, Chiappetta, Gennaro, Esposito, Franca, Ferrandina, Gabriella, Franco, Renato, Mezzanzanica, Delia, Sonego, Maura, Zulato, Elisabetta, Zannoni, Gian F., Canzonieri, Vincenzo, Scambia, Giovanni, Sorio, Roberto, Savarese, Antonella, Breda, Enrico, Scollo, Paolo, Ferro, Antonella, Tamberi, Stefano, Febbraro, Antonio, Natale, Donato, Maio, Massimo Di, Califano, Daniela, Scognamiglio, Giosuè, Lorusso, Domenica, Canevari, Silvana, Losito, Simona, Gallo, Ciro, Pignata, Sandro
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Impact Journals LLC 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5341934/
https://www.ncbi.nlm.nih.gov/pubmed/27655643
http://dx.doi.org/10.18632/oncotarget.12056
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author Perrone, Francesco
Baldassarre, Gustavo
Indraccolo, Stefano
Signoriello, Simona
Chiappetta, Gennaro
Esposito, Franca
Ferrandina, Gabriella
Franco, Renato
Mezzanzanica, Delia
Sonego, Maura
Zulato, Elisabetta
Zannoni, Gian F.
Canzonieri, Vincenzo
Scambia, Giovanni
Sorio, Roberto
Savarese, Antonella
Breda, Enrico
Scollo, Paolo
Ferro, Antonella
Tamberi, Stefano
Febbraro, Antonio
Natale, Donato
Maio, Massimo Di
Califano, Daniela
Scognamiglio, Giosuè
Lorusso, Domenica
Canevari, Silvana
Losito, Simona
Gallo, Ciro
Pignata, Sandro
author_facet Perrone, Francesco
Baldassarre, Gustavo
Indraccolo, Stefano
Signoriello, Simona
Chiappetta, Gennaro
Esposito, Franca
Ferrandina, Gabriella
Franco, Renato
Mezzanzanica, Delia
Sonego, Maura
Zulato, Elisabetta
Zannoni, Gian F.
Canzonieri, Vincenzo
Scambia, Giovanni
Sorio, Roberto
Savarese, Antonella
Breda, Enrico
Scollo, Paolo
Ferro, Antonella
Tamberi, Stefano
Febbraro, Antonio
Natale, Donato
Maio, Massimo Di
Califano, Daniela
Scognamiglio, Giosuè
Lorusso, Domenica
Canevari, Silvana
Losito, Simona
Gallo, Ciro
Pignata, Sandro
author_sort Perrone, Francesco
collection PubMed
description BACKGROUND: No biomarker is available to predict prognosis of patients with advanced ovarian cancer (AOC) and guide the choice of chemotherapy. We performed a prospective-retrospective biomarker study within the MITO2 trial on the treatment of AOC. Patients and methods: MITO2 is a randomised multicentre phase 3 trial conducted with 820 AOC patients assigned carboplatin/paclitaxel (carboplatin: AUC5, paclitaxel: 175 mg/m², every 3 weeks for 6 cycles) or carboplatin/PLD-pegylated liposomal doxorubicin (carboplatin: AUC5, PLD: 30 mg/m², every 3 weeks for 6 cycles) as first line treatment. Sixteen biomarkers (pathways of adhesion/invasion, apoptosis, transcription regulation, metabolism, and DNA repair) were studied in 229 patients, in a tissue microarray. Progression-free and overall survival were analysed with multivariable Cox model. RESULTS: After 72 months median follow-up, 594 progressions and 426 deaths were reported; there was no significant difference between the two arms in the whole trial. No biomarker had significant prognostic value. Statistically significant interactions with treatment were found for DNA-dependent protein kinase (DNA-PK) and phosphorylated acetyl-coenzymeA carboxylase (pACC), both predicting worse outcome for patients receiving carboplatin/paclitaxel. CONCLUSION: These data show that in presence of DNA-PK or pACC overexpression, carboplatin/paclitaxel might be less effective than carboplatin/PLD as first line treatment of ovarian cancer patients. Further validation of these findings is warranted.
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spelling pubmed-53419342017-03-27 Biomarker analysis of the MITO2 phase III trial of first-line treatment in ovarian cancer: predictive value of DNA-PK and phosphorylated ACC Perrone, Francesco Baldassarre, Gustavo Indraccolo, Stefano Signoriello, Simona Chiappetta, Gennaro Esposito, Franca Ferrandina, Gabriella Franco, Renato Mezzanzanica, Delia Sonego, Maura Zulato, Elisabetta Zannoni, Gian F. Canzonieri, Vincenzo Scambia, Giovanni Sorio, Roberto Savarese, Antonella Breda, Enrico Scollo, Paolo Ferro, Antonella Tamberi, Stefano Febbraro, Antonio Natale, Donato Maio, Massimo Di Califano, Daniela Scognamiglio, Giosuè Lorusso, Domenica Canevari, Silvana Losito, Simona Gallo, Ciro Pignata, Sandro Oncotarget Research Paper BACKGROUND: No biomarker is available to predict prognosis of patients with advanced ovarian cancer (AOC) and guide the choice of chemotherapy. We performed a prospective-retrospective biomarker study within the MITO2 trial on the treatment of AOC. Patients and methods: MITO2 is a randomised multicentre phase 3 trial conducted with 820 AOC patients assigned carboplatin/paclitaxel (carboplatin: AUC5, paclitaxel: 175 mg/m², every 3 weeks for 6 cycles) or carboplatin/PLD-pegylated liposomal doxorubicin (carboplatin: AUC5, PLD: 30 mg/m², every 3 weeks for 6 cycles) as first line treatment. Sixteen biomarkers (pathways of adhesion/invasion, apoptosis, transcription regulation, metabolism, and DNA repair) were studied in 229 patients, in a tissue microarray. Progression-free and overall survival were analysed with multivariable Cox model. RESULTS: After 72 months median follow-up, 594 progressions and 426 deaths were reported; there was no significant difference between the two arms in the whole trial. No biomarker had significant prognostic value. Statistically significant interactions with treatment were found for DNA-dependent protein kinase (DNA-PK) and phosphorylated acetyl-coenzymeA carboxylase (pACC), both predicting worse outcome for patients receiving carboplatin/paclitaxel. CONCLUSION: These data show that in presence of DNA-PK or pACC overexpression, carboplatin/paclitaxel might be less effective than carboplatin/PLD as first line treatment of ovarian cancer patients. Further validation of these findings is warranted. Impact Journals LLC 2016-09-15 /pmc/articles/PMC5341934/ /pubmed/27655643 http://dx.doi.org/10.18632/oncotarget.12056 Text en Copyright: © 2016 Perrone et al. http://creativecommons.org/licenses/by/3.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Paper
Perrone, Francesco
Baldassarre, Gustavo
Indraccolo, Stefano
Signoriello, Simona
Chiappetta, Gennaro
Esposito, Franca
Ferrandina, Gabriella
Franco, Renato
Mezzanzanica, Delia
Sonego, Maura
Zulato, Elisabetta
Zannoni, Gian F.
Canzonieri, Vincenzo
Scambia, Giovanni
Sorio, Roberto
Savarese, Antonella
Breda, Enrico
Scollo, Paolo
Ferro, Antonella
Tamberi, Stefano
Febbraro, Antonio
Natale, Donato
Maio, Massimo Di
Califano, Daniela
Scognamiglio, Giosuè
Lorusso, Domenica
Canevari, Silvana
Losito, Simona
Gallo, Ciro
Pignata, Sandro
Biomarker analysis of the MITO2 phase III trial of first-line treatment in ovarian cancer: predictive value of DNA-PK and phosphorylated ACC
title Biomarker analysis of the MITO2 phase III trial of first-line treatment in ovarian cancer: predictive value of DNA-PK and phosphorylated ACC
title_full Biomarker analysis of the MITO2 phase III trial of first-line treatment in ovarian cancer: predictive value of DNA-PK and phosphorylated ACC
title_fullStr Biomarker analysis of the MITO2 phase III trial of first-line treatment in ovarian cancer: predictive value of DNA-PK and phosphorylated ACC
title_full_unstemmed Biomarker analysis of the MITO2 phase III trial of first-line treatment in ovarian cancer: predictive value of DNA-PK and phosphorylated ACC
title_short Biomarker analysis of the MITO2 phase III trial of first-line treatment in ovarian cancer: predictive value of DNA-PK and phosphorylated ACC
title_sort biomarker analysis of the mito2 phase iii trial of first-line treatment in ovarian cancer: predictive value of dna-pk and phosphorylated acc
topic Research Paper
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5341934/
https://www.ncbi.nlm.nih.gov/pubmed/27655643
http://dx.doi.org/10.18632/oncotarget.12056
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