Treatment of patients with aortic atherosclerotic disease with paclitaxel-associated lipid nanoparticles.
OBJECTIVE
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.


METHODS
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.


RESULTS
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.


CONCLUSIONS
Treatment with LDE-paclitaxel was tolerated by patients with cardiovascular disease and showed the potential to reduce atherosclerotic lesion size.
Instituto Dante Pazzanese de Cardiologia, São Paulo/SP, Brazil.|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.|Hospital Maringá, Maringá/Paraná, Brazil.
Afonso A
AA
Shiozaki
Instituto Dante Pazzanese de Cardiologia, São Paulo/SP, Brazil.
Tiago
T
Senra
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.
Aleksandra T
AT
Morikawa
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.
Débora F
DF
Deus
Instituto Dante Pazzanese de Cardiologia, São Paulo/SP, Brazil.
Antonio T
AT
Paladino-Filho
Instituto Dante Pazzanese de Cardiologia, São Paulo/SP, Brazil.
Ibraim M F
IM
Pinto
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.|Faculdade de Ciências Farmacêuticas da Universidade de São Paulo, São Paulo/SP, Brazil.
Raul C
RC
Maranhão
D000368:Aged; D000369:Aged, 80 and over; D000792:Angiography; D001013:Aorta, Thoracic / Q000187:drug effects; D001018:Aortic Diseases / Q000000981:diagnostic imaging / Q000188:drug therapy*; D050197:Atherosclerosis / Q000000981:diagnostic imaging / Q000188:drug therapy*; D002784:Cholesterol / Q000097:blood / Q000627:therapeutic use*; D016503:Drug Delivery Systems; D005217:Fat Emulsions, Intravenous / Q000627:therapeutic use; D005260:Female; D006801:Humans; D008297:Male; D061330:Multidetector Computed Tomography; D053758:Nanoparticles / Q000627:therapeutic use*; D017239:Paclitaxel / Q000627:therapeutic use*; D015203:Reproducibility of Results; D013997:Time Factors; D016896:Treatment Outcome; D014280:Triglycerides / Q000097:blood; D050257:Tubulin Modulators / Q000627:therapeutic use*
D005217:Fat Emulsions, Intravenous; D014280:Triglycerides; D050257:Tubulin Modulators; D002784:Cholesterol; D017239:Paclitaxel