Microvascular Function in Patients Undergoing 5-Fluorouracil Chemotherapy
- Conditions
- Chemotherapy EffectGastrointestinal CancerHead and Neck CancerBreast Cancer5-Fluorouracil Toxicity
- Interventions
- Other: Arterial blood pressureOther: Skin microcirculatory blood flowOther: Brachial artery blood flowOther: Venous blood draw
- Registration Number
- NCT04042298
- Lead Sponsor
- Kansas State University
- Brief Summary
The primary aim of this study is to investigate potential differences in vascular function between patients receiving 5-Fluorouracil (5-FU) chemotherapy, patients receiving chemotherapies other than 5-FU, cancer survivors who were treated with 5-FU, and an age and sex matched control. 5-FU is the third most commonly administered chemotherapeutic agent and its use is associated with the second most occurrences of cardiotoxicity. Despite the known cardiotoxic effects of 5-FU, it's effects on the human vasculature are not well understood.
To achieve the goals of this project Laser Doppler flowmetry (LDF) will be used to assess blood flow within the skin microcirculation of the forearm in cancer patients who have received 5-Fluoruracil within the past 30 days (Experimental Group), cancer patients receiving radiotherapy and/or chemotherapy other than 5-Fluorouracil, and an age and sex matched control (Control Group). LDF utilizes a small (\~3 cm) non-invasive sensor placed on the skin. The sensor shines light into the skin, and upon contact with red blood cells (RBCs), the light is reflected and scattered. This information is used to evaluate microvascular blood flow and has previously been used in clinical populations.
- Detailed Description
Although cancer continues to be one of the leading causes of death each year, advancements in cancer treatments and detection have improved patient prognosis across a large number of cancer types. This trend of improved survival rates has made apparent the significant risk of chemotherapy on the cardiovascular system in such a way that cardiotoxicity has become a prime concern in cancer survivors. Indeed, cardiotoxic events have been related to numerous chemotherapy types, including the commonly used 5-Fluorouracil (5-FU). 5-FU is the third most commonly administered form of chemotherapy used in the treatment of solid malignancies. Despite undeniable effectiveness in treating cancer, administration of 5-FU is associated with the second highest incidence of cardiotoxicity out of all chemotherapeutic agents.
Such cardiotoxic manifestations typically appear in the form of chest pain, angina during rest and/or exertion, and acute coronary syndromes, however, other events such as arrythmias, myocarditis, pericarditis, heart failure, or even death have been reported following 5-FU administration. While multiple mechanisms are believed to lead to 5-FU cardiotoxicity, the effects 5-FU has on the vasculature seem to be of particular importance. Initial findings suggest these drugs have a direct toxic effect on the vascular endothelium and smooth muscle, likely through increases in reactive oxygen species (ROS). ROS are known to adversely affect endothelium independent and dependent factors which influence vascular tone. Along with increased ROS, decreases in antioxidant capacity following 5-FU therapy lead to increased vasospasms and altered vasodilator/constrictor responses. Indeed, both coronary artery vasospasms and brachial artery vasoconstriction have been found to occur in some groups directly after injection of 5-FU.
Although the primary signaling pathways for 5-FU induced cardiotoxicity are well documented, many of these studies have been conducted in animal models. Previous work has demonstrated substantial vascular dysfunction in current cancer patients undergoing adjuvant systematic chemotherapy when compared to healthy controls, however, alike investigations specifically focused on vascular dysfunction in patients receiving 5-FU have yet to be conducted. To investigate such mechanisms, microvascular reactivity will be measured with laser Doppler flowmetry combined with iontophoresis of acetylcholine in cancer patients currently undergoing treatment with 5-Fluorouracil, patients receiving chemotherapy treatments other than 5-Fluorouracil, cancer survivors previously treated with 5-Fluorouracil, and age and sex matched controls.
Recruitment & Eligibility
- Status
- UNKNOWN
- Sex
- All
- Target Recruitment
- 106
- Give voluntary consent to participate in the study
- (Group 1) Current cancer treatment includes 5-FU
- (Group 2) Current cancer treatment does not include 5-FU
- (Group 3) Cancer survivor previously treated with 5-FU but has not received cancer treatment in the year proceeding enrollment.
- (Group 4) Age, sex, and health matched (excluding cancer) control for Group 1
- (Groups 1, 2, and 4) Have received cancer treatment outside of the past year
- Not met above criteria
- Pregnant, breastfeeding, or planning to become pregnant
- Unable to provide informed consent
Study & Design
- Study Type
- OBSERVATIONAL
- Study Design
- Not specified
- Arm && Interventions
Group Intervention Description Age/Sex matched Control (Control) Arterial blood pressure Age, biological sex, and prior health history (excluding cancer diagnosis) matched control for cancer patients Age/Sex matched Control (Control) Skin microcirculatory blood flow Age, biological sex, and prior health history (excluding cancer diagnosis) matched control for cancer patients 5-FU Chemotherapy Cancer Survivor (Survivor) Skin microcirculatory blood flow Cancer survivors who have not received cancer therapy during the past year but previously received 5-Fluorouracil chemotherapy. 5-FU Chemotherapy (Experimental) Skin microcirculatory blood flow Comprised of newly diagnosed cancer patients 21 years or older who have received 5-FU chemotherapy within the past 30 days or are scheduled to receive 5-FU chemotherapy. Non-5-FU Chemotherapy (Sub-Control) Arterial blood pressure Comprised of newly diagnosed cancer patients 21 years or older who have received chemotherapy other than 5-FU within the past 30 days or are scheduled to receive chemotherapy other than 5-FU. Non-5-FU Chemotherapy (Sub-Control) Brachial artery blood flow Comprised of newly diagnosed cancer patients 21 years or older who have received chemotherapy other than 5-FU within the past 30 days or are scheduled to receive chemotherapy other than 5-FU. Age/Sex matched Control (Control) Brachial artery blood flow Age, biological sex, and prior health history (excluding cancer diagnosis) matched control for cancer patients Age/Sex matched Control (Control) Venous blood draw Age, biological sex, and prior health history (excluding cancer diagnosis) matched control for cancer patients 5-FU Chemotherapy (Experimental) Venous blood draw Comprised of newly diagnosed cancer patients 21 years or older who have received 5-FU chemotherapy within the past 30 days or are scheduled to receive 5-FU chemotherapy. 5-FU Chemotherapy Cancer Survivor (Survivor) Arterial blood pressure Cancer survivors who have not received cancer therapy during the past year but previously received 5-Fluorouracil chemotherapy. 5-FU Chemotherapy Cancer Survivor (Survivor) Brachial artery blood flow Cancer survivors who have not received cancer therapy during the past year but previously received 5-Fluorouracil chemotherapy. 5-FU Chemotherapy Cancer Survivor (Survivor) Venous blood draw Cancer survivors who have not received cancer therapy during the past year but previously received 5-Fluorouracil chemotherapy. 5-FU Chemotherapy (Experimental) Arterial blood pressure Comprised of newly diagnosed cancer patients 21 years or older who have received 5-FU chemotherapy within the past 30 days or are scheduled to receive 5-FU chemotherapy. 5-FU Chemotherapy (Experimental) Brachial artery blood flow Comprised of newly diagnosed cancer patients 21 years or older who have received 5-FU chemotherapy within the past 30 days or are scheduled to receive 5-FU chemotherapy. Non-5-FU Chemotherapy (Sub-Control) Skin microcirculatory blood flow Comprised of newly diagnosed cancer patients 21 years or older who have received chemotherapy other than 5-FU within the past 30 days or are scheduled to receive chemotherapy other than 5-FU. Non-5-FU Chemotherapy (Sub-Control) Venous blood draw Comprised of newly diagnosed cancer patients 21 years or older who have received chemotherapy other than 5-FU within the past 30 days or are scheduled to receive chemotherapy other than 5-FU.
- Primary Outcome Measures
Name Time Method Cutaneous (skin) blood flow (%) following administration of vasoactive substances 1 day Measured once in each group following administration of vasodilatory (Acetylcholine) and vasoconstrictive (Norepinepherine or Phenylephrine) substances.
Brachial artery flow mediated dilation (FMD) 1 day Measured once in each group
- Secondary Outcome Measures
Name Time Method Arterial blood pressure 1 day Systolic, diastolic, and mean arterial pressure will be measured continuously over the course of the visit for each group.
Trial Locations
- Locations (1)
Lafene Health Center
🇺🇸Manhattan, Kansas, United States