Phase Ii randomized, double-blind, placebo-controlled study of whole-brain irradiation with concomitant chloroquine for brain metastases

Background and purpose: Chloroquine (CLQ), an antimalarial drug, has a lysosomotropic effect associated with increased radiationsensibility, which is mediated by the leakage of hydrolytic enzymes, increased apoptosis, autophagy and increased oxidative stress in vitro. In this phase II study, we eval...

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Autor Principal: Rojas Puentes, Luis Leonardo; Arce Salinas, Claudia; Arrieta, Óscar; Crismatt, Alejando; Dorantes Gallareta, Yusmiren; Gamboa Vignolle, Carlos; González Pinedo, Marcelino; Núñez Gómez, Rodrigo; Ortega Gómez, Alette
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Publicado: Radiation Oncology; Vol. 8 2013
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Acceso en línea:http://babel.banrepcultural.org/cdm/ref/collection/p17054coll23/id/707
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spelling ir-p17054coll23-7072020-09-29 Phase Ii randomized, double-blind, placebo-controlled study of whole-brain irradiation with concomitant chloroquine for brain metastases Rojas Puentes, Luis Leonardo; Arce Salinas, Claudia; Arrieta, Óscar; Crismatt, Alejando; Dorantes Gallareta, Yusmiren; Gamboa Vignolle, Carlos; González Pinedo, Marcelino; Núñez Gómez, Rodrigo; Ortega Gómez, Alette Background and purpose: Chloroquine (CLQ), an antimalarial drug, has a lysosomotropic effect associated with increased radiationsensibility, which is mediated by the leakage of hydrolytic enzymes, increased apoptosis, autophagy and increased oxidative stress in vitro. In this phase II study, we evaluated the efficacy and safety of radiosensibilization using CLQ concomitant with 30 Gray (Gy) of whole-brain irradiation (WBI) to treat patients with brain metastases (BM) from solid tumors. Methods: Seventy-three eligible patients were randomized. Thirty-nine patients received WBI (30 Gy in 10 fractions over 2 weeks) concomitant with 150 mg of CLQ for 4 weeks (the CLQ arm). Thirty-four patients received the same schedule of WBI concomitant with a placebo for 4 weeks (the control arm). All the patients were evaluated for quality of life (QoL) using the EORTC Quality of Life (QoL) Questionnaire (EORTC QLQ-C30) (Mexican version) beforebeginning radiotherapy and one month later. Results: The overall response rate (ORR) was 54% for the CLQ arm and 55% for the control arm (p=0.92). The progression-free survival of brain metastases (BMPFS) rates at one year were 83.9% (95% CI 69.4-98.4) for the CLQ arm and 55.1% (95% CI 33.6-77.6) for the control arm. Treatment with CLQ was independently associated with increased BMPFS (RR 0.31,95% CI [0.1-0.9], p=0.046).The only factor that was independently associated with increased overall survival (OS) was the presence of< 4 brain metastases (RR 1.9, 95% CI [1.12-3.3], p=0.017). WBI was associated with improvements in cognitive and emotional function but also with worsened nausea in both patients groups. No differences in QoL or toxicity were found between the study arms. Conclusion: Treatment with CLQ plus WBI improved the control of BM (compared with the control arm) with no increase in toxicity; however, CLQ did not improve the RR or OS. A phase III clinical trial is warranted to confirm these findings. Brain metastases; Radiation therapy; Chloroquine; Whole-brain radiation; Radiosensibilization Tecnología; Tecnología / Ciencias médicas Medicina 2013 Radiation Oncology; Vol. 8 PDF Artículo ENG - Inglés Colfuturo © Derechos reservados del autor http://babel.banrepcultural.org/cdm/ref/collection/p17054coll23/id/707
institution Biblioteca Virtual Banco de la República - Colecciones digitales
collection Custom
language Desconocido (Unknown)
topic Brain metastases; Radiation therapy; Chloroquine; Whole-brain radiation; Radiosensibilization
Tecnología; Tecnología / Ciencias médicas Medicina
spellingShingle Brain metastases; Radiation therapy; Chloroquine; Whole-brain radiation; Radiosensibilization
Tecnología; Tecnología / Ciencias médicas Medicina
Rojas Puentes, Luis Leonardo; Arce Salinas, Claudia; Arrieta, Óscar; Crismatt, Alejando; Dorantes Gallareta, Yusmiren; Gamboa Vignolle, Carlos; González Pinedo, Marcelino; Núñez Gómez, Rodrigo; Ortega Gómez, Alette
Phase Ii randomized, double-blind, placebo-controlled study of whole-brain irradiation with concomitant chloroquine for brain metastases
description Background and purpose: Chloroquine (CLQ), an antimalarial drug, has a lysosomotropic effect associated with increased radiationsensibility, which is mediated by the leakage of hydrolytic enzymes, increased apoptosis, autophagy and increased oxidative stress in vitro. In this phase II study, we evaluated the efficacy and safety of radiosensibilization using CLQ concomitant with 30 Gray (Gy) of whole-brain irradiation (WBI) to treat patients with brain metastases (BM) from solid tumors. Methods: Seventy-three eligible patients were randomized. Thirty-nine patients received WBI (30 Gy in 10 fractions over 2 weeks) concomitant with 150 mg of CLQ for 4 weeks (the CLQ arm). Thirty-four patients received the same schedule of WBI concomitant with a placebo for 4 weeks (the control arm). All the patients were evaluated for quality of life (QoL) using the EORTC Quality of Life (QoL) Questionnaire (EORTC QLQ-C30) (Mexican version) beforebeginning radiotherapy and one month later. Results: The overall response rate (ORR) was 54% for the CLQ arm and 55% for the control arm (p=0.92). The progression-free survival of brain metastases (BMPFS) rates at one year were 83.9% (95% CI 69.4-98.4) for the CLQ arm and 55.1% (95% CI 33.6-77.6) for the control arm. Treatment with CLQ was independently associated with increased BMPFS (RR 0.31,95% CI [0.1-0.9], p=0.046).The only factor that was independently associated with increased overall survival (OS) was the presence of< 4 brain metastases (RR 1.9, 95% CI [1.12-3.3], p=0.017). WBI was associated with improvements in cognitive and emotional function but also with worsened nausea in both patients groups. No differences in QoL or toxicity were found between the study arms. Conclusion: Treatment with CLQ plus WBI improved the control of BM (compared with the control arm) with no increase in toxicity; however, CLQ did not improve the RR or OS. A phase III clinical trial is warranted to confirm these findings.
format Artículo (Article)
author Rojas Puentes, Luis Leonardo; Arce Salinas, Claudia; Arrieta, Óscar; Crismatt, Alejando; Dorantes Gallareta, Yusmiren; Gamboa Vignolle, Carlos; González Pinedo, Marcelino; Núñez Gómez, Rodrigo; Ortega Gómez, Alette
author_facet Rojas Puentes, Luis Leonardo; Arce Salinas, Claudia; Arrieta, Óscar; Crismatt, Alejando; Dorantes Gallareta, Yusmiren; Gamboa Vignolle, Carlos; González Pinedo, Marcelino; Núñez Gómez, Rodrigo; Ortega Gómez, Alette
author_sort Rojas Puentes, Luis Leonardo; Arce Salinas, Claudia; Arrieta, Óscar; Crismatt, Alejando; Dorantes Gallareta, Yusmiren; Gamboa Vignolle, Carlos; González Pinedo, Marcelino; Núñez Gómez, Rodrigo; Ortega Gómez, Alette
title Phase Ii randomized, double-blind, placebo-controlled study of whole-brain irradiation with concomitant chloroquine for brain metastases
title_short Phase Ii randomized, double-blind, placebo-controlled study of whole-brain irradiation with concomitant chloroquine for brain metastases
title_full Phase Ii randomized, double-blind, placebo-controlled study of whole-brain irradiation with concomitant chloroquine for brain metastases
title_fullStr Phase Ii randomized, double-blind, placebo-controlled study of whole-brain irradiation with concomitant chloroquine for brain metastases
title_full_unstemmed Phase Ii randomized, double-blind, placebo-controlled study of whole-brain irradiation with concomitant chloroquine for brain metastases
title_sort phase ii randomized, double-blind, placebo-controlled study of whole-brain irradiation with concomitant chloroquine for brain metastases
publisher Radiation Oncology; Vol. 8
publishDate 2013
url http://babel.banrepcultural.org/cdm/ref/collection/p17054coll23/id/707
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