Cargando…

Long-Term Cardiac Safety and Survival Outcomes of Neoadjuvant Pegylated Liposomal Doxorubicin in Elderly Patients or Prone to Cardiotoxicity and Triple Negative Breast Cancer. Final Results of the Multicentre Phase II CAPRICE Study

BACKGROUND: The CAPRICE trial was designed to specifically evaluate neoadjuvant pegylated liposomal doxorubicin (PLD) in elderly patients or in those with other cardiovascular risk factors in whom conventional doxorubicin was contraindicated. The primary analysis of the study showed a pathological c...

Descripción completa

Detalles Bibliográficos
Autores principales: Gil-Gil, Miguel J., Bellet, Meritxell, Bergamino, Milana, Morales, Serafín, Barnadas, Agustí, Manso, Luís, Saura, Cristina, Fernández-Ortega, Adela, Garcia-Martinez, Elena, Martinez-Jañez, Noelia, Melé, Mireia, Villagrasa, Patricia, Celiz, Pamela, Perez Martin, X., Ciruelos, Eva, Pernas, Sonia
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8300427/
https://www.ncbi.nlm.nih.gov/pubmed/34307126
http://dx.doi.org/10.3389/fonc.2021.645026
_version_ 1783726471123042304
author Gil-Gil, Miguel J.
Bellet, Meritxell
Bergamino, Milana
Morales, Serafín
Barnadas, Agustí
Manso, Luís
Saura, Cristina
Fernández-Ortega, Adela
Garcia-Martinez, Elena
Martinez-Jañez, Noelia
Melé, Mireia
Villagrasa, Patricia
Celiz, Pamela
Perez Martin, X.
Ciruelos, Eva
Pernas, Sonia
author_facet Gil-Gil, Miguel J.
Bellet, Meritxell
Bergamino, Milana
Morales, Serafín
Barnadas, Agustí
Manso, Luís
Saura, Cristina
Fernández-Ortega, Adela
Garcia-Martinez, Elena
Martinez-Jañez, Noelia
Melé, Mireia
Villagrasa, Patricia
Celiz, Pamela
Perez Martin, X.
Ciruelos, Eva
Pernas, Sonia
author_sort Gil-Gil, Miguel J.
collection PubMed
description BACKGROUND: The CAPRICE trial was designed to specifically evaluate neoadjuvant pegylated liposomal doxorubicin (PLD) in elderly patients or in those with other cardiovascular risk factors in whom conventional doxorubicin was contraindicated. The primary analysis of the study showed a pathological complete response (pCR) of 32% and no significant decreases in LVEF during chemotherapy. Here, we report important secondary study objectives: 5-year cardiac safety, disease-free survival (DFS), overall survival (OS) and breast cancer specific survival (BCSS). METHODS: In this multicentre, single-arm, phase II trial, elderly patients or those prone to cardiotoxicity and high risk stage II-IIIB breast cancer received PLD (35 mg/m(2)) plus cyclophosphamide (600 mg/m(2)) every 4 weeks for 4 cycles, followed by paclitaxel for 12 weeks as neoadjuvant chemotherapy (NAC). Left ventricular ejection fraction (LVEF) monitorization, electrocardiograms and cardiac questionnaires were performed at baseline, during treatment and at 9, 16, 28 and 40 weeks thereafter. The primary endpoint was pCR and 5-year cardiac safety, DFS, BCSS and OS were also analyzed. RESULTS: Between Oct 2007, and Jun 2010, 50 eligible patients were included. Median age was 73 (35-84) years, 84% were older than 65; 64% of patients suffered from hypertension, and 10% had prior cardiac disease. Most of tumors (88%) were triple negative. No significant decreases in LVEF were observed. The mean baseline LVEF was 66.6% (52-86) and after a median follow-up of 5 years, mean LVEF was 66 (54.5-73). For intention to treat population, 5-year DFS was 50% (95% CI 40.2-68.1) and 5-year OS was 56% (95%CI 41.2-68.4). There were 8 non-cancer related deaths, achieving a 5 years BCSS of 67.74% (CI 95%:54.31%- 81.18%). CONCLUSION: At 5-year follow-up, this PLD-based NAC regimen continued to be cardiac-safe and effective in a population of very high-risk breast cancer patients. This scheme should be considered as an option in elderly patients or in those with other risks of developing cardiotoxicity. TRIAL REGISTRATION NUMBER: ClinicalTrials.gov reference NCT00563953.
format Online
Article
Text
id pubmed-8300427
institution National Center for Biotechnology Information
language English
publishDate 2021
publisher Frontiers Media S.A.
record_format MEDLINE/PubMed
spelling pubmed-83004272021-07-24 Long-Term Cardiac Safety and Survival Outcomes of Neoadjuvant Pegylated Liposomal Doxorubicin in Elderly Patients or Prone to Cardiotoxicity and Triple Negative Breast Cancer. Final Results of the Multicentre Phase II CAPRICE Study Gil-Gil, Miguel J. Bellet, Meritxell Bergamino, Milana Morales, Serafín Barnadas, Agustí Manso, Luís Saura, Cristina Fernández-Ortega, Adela Garcia-Martinez, Elena Martinez-Jañez, Noelia Melé, Mireia Villagrasa, Patricia Celiz, Pamela Perez Martin, X. Ciruelos, Eva Pernas, Sonia Front Oncol Oncology BACKGROUND: The CAPRICE trial was designed to specifically evaluate neoadjuvant pegylated liposomal doxorubicin (PLD) in elderly patients or in those with other cardiovascular risk factors in whom conventional doxorubicin was contraindicated. The primary analysis of the study showed a pathological complete response (pCR) of 32% and no significant decreases in LVEF during chemotherapy. Here, we report important secondary study objectives: 5-year cardiac safety, disease-free survival (DFS), overall survival (OS) and breast cancer specific survival (BCSS). METHODS: In this multicentre, single-arm, phase II trial, elderly patients or those prone to cardiotoxicity and high risk stage II-IIIB breast cancer received PLD (35 mg/m(2)) plus cyclophosphamide (600 mg/m(2)) every 4 weeks for 4 cycles, followed by paclitaxel for 12 weeks as neoadjuvant chemotherapy (NAC). Left ventricular ejection fraction (LVEF) monitorization, electrocardiograms and cardiac questionnaires were performed at baseline, during treatment and at 9, 16, 28 and 40 weeks thereafter. The primary endpoint was pCR and 5-year cardiac safety, DFS, BCSS and OS were also analyzed. RESULTS: Between Oct 2007, and Jun 2010, 50 eligible patients were included. Median age was 73 (35-84) years, 84% were older than 65; 64% of patients suffered from hypertension, and 10% had prior cardiac disease. Most of tumors (88%) were triple negative. No significant decreases in LVEF were observed. The mean baseline LVEF was 66.6% (52-86) and after a median follow-up of 5 years, mean LVEF was 66 (54.5-73). For intention to treat population, 5-year DFS was 50% (95% CI 40.2-68.1) and 5-year OS was 56% (95%CI 41.2-68.4). There were 8 non-cancer related deaths, achieving a 5 years BCSS of 67.74% (CI 95%:54.31%- 81.18%). CONCLUSION: At 5-year follow-up, this PLD-based NAC regimen continued to be cardiac-safe and effective in a population of very high-risk breast cancer patients. This scheme should be considered as an option in elderly patients or in those with other risks of developing cardiotoxicity. TRIAL REGISTRATION NUMBER: ClinicalTrials.gov reference NCT00563953. Frontiers Media S.A. 2021-07-09 /pmc/articles/PMC8300427/ /pubmed/34307126 http://dx.doi.org/10.3389/fonc.2021.645026 Text en Copyright © 2021 Gil-Gil, Bellet, Bergamino, Morales, Barnadas, Manso, Saura, Fernández-Ortega, Garcia-Martinez, Martinez-Jañez, Melé, Villagrasa, Celiz, Perez Martin, Ciruelos and Pernas https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Oncology
Gil-Gil, Miguel J.
Bellet, Meritxell
Bergamino, Milana
Morales, Serafín
Barnadas, Agustí
Manso, Luís
Saura, Cristina
Fernández-Ortega, Adela
Garcia-Martinez, Elena
Martinez-Jañez, Noelia
Melé, Mireia
Villagrasa, Patricia
Celiz, Pamela
Perez Martin, X.
Ciruelos, Eva
Pernas, Sonia
Long-Term Cardiac Safety and Survival Outcomes of Neoadjuvant Pegylated Liposomal Doxorubicin in Elderly Patients or Prone to Cardiotoxicity and Triple Negative Breast Cancer. Final Results of the Multicentre Phase II CAPRICE Study
title Long-Term Cardiac Safety and Survival Outcomes of Neoadjuvant Pegylated Liposomal Doxorubicin in Elderly Patients or Prone to Cardiotoxicity and Triple Negative Breast Cancer. Final Results of the Multicentre Phase II CAPRICE Study
title_full Long-Term Cardiac Safety and Survival Outcomes of Neoadjuvant Pegylated Liposomal Doxorubicin in Elderly Patients or Prone to Cardiotoxicity and Triple Negative Breast Cancer. Final Results of the Multicentre Phase II CAPRICE Study
title_fullStr Long-Term Cardiac Safety and Survival Outcomes of Neoadjuvant Pegylated Liposomal Doxorubicin in Elderly Patients or Prone to Cardiotoxicity and Triple Negative Breast Cancer. Final Results of the Multicentre Phase II CAPRICE Study
title_full_unstemmed Long-Term Cardiac Safety and Survival Outcomes of Neoadjuvant Pegylated Liposomal Doxorubicin in Elderly Patients or Prone to Cardiotoxicity and Triple Negative Breast Cancer. Final Results of the Multicentre Phase II CAPRICE Study
title_short Long-Term Cardiac Safety and Survival Outcomes of Neoadjuvant Pegylated Liposomal Doxorubicin in Elderly Patients or Prone to Cardiotoxicity and Triple Negative Breast Cancer. Final Results of the Multicentre Phase II CAPRICE Study
title_sort long-term cardiac safety and survival outcomes of neoadjuvant pegylated liposomal doxorubicin in elderly patients or prone to cardiotoxicity and triple negative breast cancer. final results of the multicentre phase ii caprice study
topic Oncology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8300427/
https://www.ncbi.nlm.nih.gov/pubmed/34307126
http://dx.doi.org/10.3389/fonc.2021.645026
work_keys_str_mv AT gilgilmiguelj longtermcardiacsafetyandsurvivaloutcomesofneoadjuvantpegylatedliposomaldoxorubicininelderlypatientsorpronetocardiotoxicityandtriplenegativebreastcancerfinalresultsofthemulticentrephaseiicapricestudy
AT belletmeritxell longtermcardiacsafetyandsurvivaloutcomesofneoadjuvantpegylatedliposomaldoxorubicininelderlypatientsorpronetocardiotoxicityandtriplenegativebreastcancerfinalresultsofthemulticentrephaseiicapricestudy
AT bergaminomilana longtermcardiacsafetyandsurvivaloutcomesofneoadjuvantpegylatedliposomaldoxorubicininelderlypatientsorpronetocardiotoxicityandtriplenegativebreastcancerfinalresultsofthemulticentrephaseiicapricestudy
AT moralesserafin longtermcardiacsafetyandsurvivaloutcomesofneoadjuvantpegylatedliposomaldoxorubicininelderlypatientsorpronetocardiotoxicityandtriplenegativebreastcancerfinalresultsofthemulticentrephaseiicapricestudy
AT barnadasagusti longtermcardiacsafetyandsurvivaloutcomesofneoadjuvantpegylatedliposomaldoxorubicininelderlypatientsorpronetocardiotoxicityandtriplenegativebreastcancerfinalresultsofthemulticentrephaseiicapricestudy
AT mansoluis longtermcardiacsafetyandsurvivaloutcomesofneoadjuvantpegylatedliposomaldoxorubicininelderlypatientsorpronetocardiotoxicityandtriplenegativebreastcancerfinalresultsofthemulticentrephaseiicapricestudy
AT sauracristina longtermcardiacsafetyandsurvivaloutcomesofneoadjuvantpegylatedliposomaldoxorubicininelderlypatientsorpronetocardiotoxicityandtriplenegativebreastcancerfinalresultsofthemulticentrephaseiicapricestudy
AT fernandezortegaadela longtermcardiacsafetyandsurvivaloutcomesofneoadjuvantpegylatedliposomaldoxorubicininelderlypatientsorpronetocardiotoxicityandtriplenegativebreastcancerfinalresultsofthemulticentrephaseiicapricestudy
AT garciamartinezelena longtermcardiacsafetyandsurvivaloutcomesofneoadjuvantpegylatedliposomaldoxorubicininelderlypatientsorpronetocardiotoxicityandtriplenegativebreastcancerfinalresultsofthemulticentrephaseiicapricestudy
AT martinezjaneznoelia longtermcardiacsafetyandsurvivaloutcomesofneoadjuvantpegylatedliposomaldoxorubicininelderlypatientsorpronetocardiotoxicityandtriplenegativebreastcancerfinalresultsofthemulticentrephaseiicapricestudy
AT melemireia longtermcardiacsafetyandsurvivaloutcomesofneoadjuvantpegylatedliposomaldoxorubicininelderlypatientsorpronetocardiotoxicityandtriplenegativebreastcancerfinalresultsofthemulticentrephaseiicapricestudy
AT villagrasapatricia longtermcardiacsafetyandsurvivaloutcomesofneoadjuvantpegylatedliposomaldoxorubicininelderlypatientsorpronetocardiotoxicityandtriplenegativebreastcancerfinalresultsofthemulticentrephaseiicapricestudy
AT celizpamela longtermcardiacsafetyandsurvivaloutcomesofneoadjuvantpegylatedliposomaldoxorubicininelderlypatientsorpronetocardiotoxicityandtriplenegativebreastcancerfinalresultsofthemulticentrephaseiicapricestudy
AT perezmartinx longtermcardiacsafetyandsurvivaloutcomesofneoadjuvantpegylatedliposomaldoxorubicininelderlypatientsorpronetocardiotoxicityandtriplenegativebreastcancerfinalresultsofthemulticentrephaseiicapricestudy
AT cirueloseva longtermcardiacsafetyandsurvivaloutcomesofneoadjuvantpegylatedliposomaldoxorubicininelderlypatientsorpronetocardiotoxicityandtriplenegativebreastcancerfinalresultsofthemulticentrephaseiicapricestudy
AT pernassonia longtermcardiacsafetyandsurvivaloutcomesofneoadjuvantpegylatedliposomaldoxorubicininelderlypatientsorpronetocardiotoxicityandtriplenegativebreastcancerfinalresultsofthemulticentrephaseiicapricestudy