Treatment of patients with aortic atherosclerotic disease with paclitaxel-associated lipid nanoparticles
Identifieur interne : 000004 ( Main/Merge ); précédent : 000003; suivant : 000005Treatment of patients with aortic atherosclerotic disease with paclitaxel-associated lipid nanoparticles
Auteurs : Afonso A. Shiozaki [Brésil] ; Tiago Senra [Brésil] ; Aleksandra T. Morikawa [Brésil] ; Débora F. Deus [Brésil] ; Antonio T. Paladino [Brésil] ; Ibraim M. F. Pinto [Brésil] ; Raul C. Maranhão [Brésil]Source :
- Clinics [ 1807-5932 ] ; 2016.
Abstract
The toxicity of anti-cancer chemotherapeutic agents can be reduced by associating these compounds, such as the anti-proliferative agent paclitaxel, with a cholesterol-rich nanoemulsion (LDE) that mimics the lipid composition of low-density lipoprotein (LDL). When injected into circulation, the LDE concentrates the carried drugs in neoplastic tissues and atherosclerotic lesions. In rabbits, atherosclerotic lesion size was reduced by 65% following LDE-paclitaxel treatment. The current study aimed to test the effectiveness of LDE-paclitaxel on inpatients with aortic atherosclerosis.
This study tested a 175 mg/m2 body surface area dose of LDE-paclitaxel (intravenous administration, 3/3 weeks for 6 cycles) in patients with aortic atherosclerosis who were aged between 69 and 86 yrs. A control group of 9 untreated patients with aortic atherosclerosis (72-83 yrs) was also observed.
The LDE-paclitaxel treatment elicited no important clinical or laboratory toxicities. Images were acquired via multiple detector computer tomography angiography (64-slice scanner) before treatment and at 1-2 months after treatment. The images showed that the mean plaque volume in the aortic artery wall was reduced in 4 of the 8 patients, while in 3 patients it remained unchanged and in one patient it increased. In the control group, images were acquired twice with an interval of 6-8 months. None of the patients in this group exhibited a reduction in plaque volume; in contrast, the plaque volume increased in three patients and remained stable in four patients. During the study period, one death unrelated to the treatment occurred in the LDE-paclitaxel group and one death occurred in the control group.
Treatment with LDE-paclitaxel was tolerated by patients with cardiovascular disease and showed the potential to reduce atherosclerotic lesion size.
Url:
DOI: 10.6061/clinics/2016(08)05
PubMed: NONE
PubMed Central: 4975788
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Shiozaki</name><affiliation wicri:level="2"><nlm:aff id="af1-cln_71p435">Instituto Dante Pazzanese de Cardiologia, São Paulo/SP, Brazil</nlm:aff><country xml:lang="fr">Brésil</country><wicri:regionArea>Instituto Dante Pazzanese de Cardiologia, São Paulo/SP</wicri:regionArea><placeName><region type="state">État de São Paulo</region></placeName></affiliation><affiliation wicri:level="4"><nlm:aff id="af2-cln_71p435">Laboratório de Metabolismo e Lípides - Instituto do Coração (InCor) do Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo, São Paulo/SP, Brazil</nlm:aff><country xml:lang="fr">Brésil</country><wicri:regionArea>Laboratório de Metabolismo e Lípides - Instituto do Coração (InCor) do Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo, São Paulo/SP</wicri:regionArea><placeName><region type="state">État de São Paulo</region><settlement type="city">São Paulo</settlement></placeName><orgName type="university">Université de São Paulo</orgName></affiliation><affiliation wicri:level="1"><nlm:aff id="af3-cln_71p435">Hospital Maringá, Maringá/Paraná, Brazil</nlm:aff><country xml:lang="fr">Brésil</country><wicri:regionArea>Hospital Maringá, Maringá/Paraná</wicri:regionArea><wicri:noRegion>Maringá/Paraná</wicri:noRegion></affiliation></author><author><name sortKey="Senra, Tiago" sort="Senra, Tiago" uniqKey="Senra T" first="Tiago" last="Senra">Tiago Senra</name><affiliation wicri:level="2"><nlm:aff id="af1-cln_71p435">Instituto Dante Pazzanese de Cardiologia, São Paulo/SP, Brazil</nlm:aff><country xml:lang="fr">Brésil</country><wicri:regionArea>Instituto Dante Pazzanese de Cardiologia, São Paulo/SP</wicri:regionArea><placeName><region type="state">État de São Paulo</region></placeName></affiliation></author><author><name sortKey="Morikawa, Aleksandra T" sort="Morikawa, Aleksandra T" uniqKey="Morikawa A" first="Aleksandra T." last="Morikawa">Aleksandra T. Morikawa</name><affiliation wicri:level="4"><nlm:aff id="af2-cln_71p435">Laboratório de Metabolismo e Lípides - Instituto do Coração (InCor) do Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo, São Paulo/SP, Brazil</nlm:aff><country xml:lang="fr">Brésil</country><wicri:regionArea>Laboratório de Metabolismo e Lípides - Instituto do Coração (InCor) do Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo, São Paulo/SP</wicri:regionArea><placeName><region type="state">État de São Paulo</region><settlement type="city">São Paulo</settlement></placeName><orgName type="university">Université de São Paulo</orgName></affiliation></author><author><name sortKey="Deus, Debora F" sort="Deus, Debora F" uniqKey="Deus D" first="Débora F." last="Deus">Débora F. Deus</name><affiliation wicri:level="4"><nlm:aff id="af2-cln_71p435">Laboratório de Metabolismo e Lípides - Instituto do Coração (InCor) do Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo, São Paulo/SP, Brazil</nlm:aff><country xml:lang="fr">Brésil</country><wicri:regionArea>Laboratório de Metabolismo e Lípides - Instituto do Coração (InCor) do Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo, São Paulo/SP</wicri:regionArea><placeName><region type="state">État de São Paulo</region><settlement type="city">São Paulo</settlement></placeName><orgName type="university">Université de São Paulo</orgName></affiliation></author><author><name sortKey="Paladino, Antonio T" sort="Paladino, Antonio T" uniqKey="Paladino A" first="Antonio T" last="Paladino">Antonio T. Paladino</name><affiliation wicri:level="2"><nlm:aff id="af1-cln_71p435">Instituto Dante Pazzanese de Cardiologia, São Paulo/SP, Brazil</nlm:aff><country xml:lang="fr">Brésil</country><wicri:regionArea>Instituto Dante Pazzanese de Cardiologia, São Paulo/SP</wicri:regionArea><placeName><region type="state">État de São Paulo</region></placeName></affiliation></author><author><name sortKey="Pinto, Ibraim M F" sort="Pinto, Ibraim M F" uniqKey="Pinto I" first="Ibraim M. F." last="Pinto">Ibraim M. F. Pinto</name><affiliation wicri:level="2"><nlm:aff id="af1-cln_71p435">Instituto Dante Pazzanese de Cardiologia, São Paulo/SP, Brazil</nlm:aff><country xml:lang="fr">Brésil</country><wicri:regionArea>Instituto Dante Pazzanese de Cardiologia, São Paulo/SP</wicri:regionArea><placeName><region type="state">État de São Paulo</region></placeName></affiliation></author><author><name sortKey="Maranhao, Raul C" sort="Maranhao, Raul C" uniqKey="Maranhao R" first="Raul C." last="Maranhão">Raul C. Maranhão</name><affiliation wicri:level="4"><nlm:aff id="af2-cln_71p435">Laboratório de Metabolismo e Lípides - Instituto do Coração (InCor) do Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo, São Paulo/SP, Brazil</nlm:aff><country xml:lang="fr">Brésil</country><wicri:regionArea>Laboratório de Metabolismo e Lípides - Instituto do Coração (InCor) do Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo, São Paulo/SP</wicri:regionArea><placeName><region type="state">État de São Paulo</region><settlement type="city">São Paulo</settlement></placeName><orgName type="university">Université de São Paulo</orgName></affiliation><affiliation wicri:level="4"><nlm:aff id="af4-cln_71p435">Faculdade de Ciências Farmacêuticas da Universidade de São Paulo, São Paulo/SP, Brazil</nlm:aff><country xml:lang="fr">Brésil</country><wicri:regionArea>Faculdade de Ciências Farmacêuticas da Universidade de São Paulo, São Paulo/SP</wicri:regionArea><placeName><region type="state">État de São Paulo</region><settlement type="city">São Paulo</settlement></placeName><orgName type="university">Université de São Paulo</orgName></affiliation></author></analytic><series><title level="j">Clinics</title><idno type="ISSN">1807-5932</idno><idno type="eISSN">1980-5322</idno><imprint><date when="2016">2016</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><sec><title>OBJECTIVE:</title><p>The toxicity of anti-cancer chemotherapeutic agents can be reduced by associating these compounds, such as the anti-proliferative agent paclitaxel, with a cholesterol-rich nanoemulsion (LDE) that mimics the lipid composition of low-density lipoprotein (LDL). When injected into circulation, the LDE concentrates the carried drugs in neoplastic tissues and atherosclerotic lesions. In rabbits, atherosclerotic lesion size was reduced by 65% following LDE-paclitaxel treatment. The current study aimed to test the effectiveness of LDE-paclitaxel on inpatients with aortic atherosclerosis.</p></sec><sec><title>METHODS:</title><p>This study tested a 175 mg/m<sup>2</sup> body surface area dose of LDE-paclitaxel (intravenous administration, 3/3 weeks for 6 cycles) in patients with aortic atherosclerosis who were aged between 69 and 86 yrs. A control group of 9 untreated patients with aortic atherosclerosis (72-83 yrs) was also observed.</p></sec><sec><title>RESULTS:</title><p>The LDE-paclitaxel treatment elicited no important clinical or laboratory toxicities. Images were acquired via multiple detector computer tomography angiography (64-slice scanner) before treatment and at 1-2 months after treatment. The images showed that the mean plaque volume in the aortic artery wall was reduced in 4 of the 8 patients, while in 3 patients it remained unchanged and in one patient it increased. In the control group, images were acquired twice with an interval of 6-8 months. None of the patients in this group exhibited a reduction in plaque volume; in contrast, the plaque volume increased in three patients and remained stable in four patients. During the study period, one death unrelated to the treatment occurred in the LDE-paclitaxel group and one death occurred in the control group.</p></sec><sec><title>CONCLUSION:</title><p>Treatment with LDE-paclitaxel was tolerated by patients with cardiovascular disease and showed the potential to reduce atherosclerotic lesion size.</p></sec></div></front><back><div1 type="bibliography"><listBibl><biblStruct><analytic><author><name sortKey="Capmany, Rp" uniqKey="Capmany R">RP Capmany</name></author><author><name sortKey="Iba Ez, Mo" uniqKey="Iba Ez M">MO Ibañez</name></author><author><name sortKey="Pesquer, Xj" uniqKey="Pesquer X">XJ Pesquer</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Fujita, S" uniqKey="Fujita S">S Fujita</name></author><author><name sortKey="Sugioka, K" uniqKey="Sugioka K">K Sugioka</name></author><author><name sortKey="Matsumura, Y" uniqKey="Matsumura Y">Y Matsumura</name></author><author><name sortKey="Ito, A" uniqKey="Ito 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sortKey="Margolis, J" uniqKey="Margolis J">J Margolis</name></author><author><name sortKey="Mcdonald, J" uniqKey="Mcdonald J">J McDonald</name></author><author><name sortKey="Heuser, R" uniqKey="Heuser R">R Heuser</name></author><author><name sortKey="Klinke, P" uniqKey="Klinke P">P Klinke</name></author><author><name sortKey="Waksman, R" uniqKey="Waksman R">R Waksman</name></author><author><name sortKey="Virmani, R" uniqKey="Virmani R">R Virmani</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Carvalho, Po" uniqKey="Carvalho P">PO Carvalho</name></author><author><name sortKey="Maranhao, Rc" uniqKey="Maranhao R">RC Maranhão</name></author><author><name sortKey="Stolf, Na" uniqKey="Stolf N">NA Stolf</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Tavares, Er" uniqKey="Tavares E">ER Tavares</name></author><author><name sortKey="Freitas, Fr" uniqKey="Freitas F">FR Freitas</name></author><author><name sortKey="Diament, 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