5-Fluorouracil for Colorectal Cancer

Overseen By Elahe Mollapour

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Inova Health Care Services

Must be taking: 5-FU

Disqualifiers: Untreated brain metastasis, DPD deficiency, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: Unknown

10 Participants Needed

Trial Summary

What is the purpose of this trial?

The purpose of this research is to see if adjusting the dose of 5-fluorouracil based on its concentration in your blood will improve the treatment of your metastatic colon cancer.

Will I have to stop taking my current medications?

The trial information does not specify if you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor.

What data supports the effectiveness of the drug 5-fluorouracil (5-FU) for colorectal cancer?

Research shows that 5-fluorouracil (5-FU) is a commonly used and effective drug for treating colorectal cancer, improving survival rates in many patients. However, its effectiveness can vary between individuals, and some patients may develop resistance to the drug. ^{1 2 3 4 5}

What are the safety concerns of using 5-Fluorouracil for colorectal cancer?

5-Fluorouracil (5-FU) can cause several side effects, including low blood cell counts (leucopenia, neutropenia, thrombocytopenia), mouth sores, diarrhea, nausea, vomiting, and hand-foot syndrome (redness and swelling of the hands and feet). It can also lead to more serious issues like liver damage and severe intestinal problems. Rarely, it may cause neurological effects like headaches and dizziness. ^{5 6 7 8 9}

How does the drug 5-fluorouracil (5-FU) differ from other treatments for colorectal cancer?

5-fluorouracil (5-FU) is a widely used drug for colorectal cancer, but its effectiveness can be limited by drug resistance and side effects like liver and digestive system toxicity. It works by targeting enzymes involved in folate metabolism, which is crucial for cancer cell growth, making it different from other treatments that may not target these specific pathways. ^{2 3 4 5 10}

Research Team

Jasmine Huynh

Principal Investigator

Inova Schar Cancer Institute

Eligibility Criteria

This trial is for individuals with metastatic colorectal cancer. Participants should be suitable for chemotherapy and have not been treated with the study drugs before. Specific details about inclusion and exclusion criteria are not provided, but typically these would relate to overall health status, prior treatments, and other medical conditions.

Inclusion Criteria

I can take care of myself but might not be able to do heavy physical work.

Life expectancy > 3 months

I haven't had treatment for cancer that has spread, but if I had 5-FU or FOLFOX, it was over 6 months ago.

Exclusion Criteria

I have brain metastases but no ongoing symptoms without steroids.

It has been over 4 weeks since my last surgery or 2 weeks since my last radiation treatment.

I have a known DPD deficiency.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Chemotherapy

Participants receive 5-FU/Leucovorin (LV) alone, with oxaliplatin or irinotecan or both, with dose adjustments based on PK assay results

8 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• 5-fluorouracil (5-FU)

Trial Overview The study is testing whether adjusting doses of the chemotherapy drug 5-fluorouracil (5-FU) based on blood concentration levels can improve outcomes in metastatic colon cancer treatment. Other chemo regimens like FOLFIRI, Modified FOLFOX6, and mFOLFOXIRI are also being tested biweekly.

Participant Groups

Group I: Chemotherapy with 5-FU/Leucovorin (LV) alone, with oxaliplatin or irinotecan or both Experimental Treatment 4 Interventions

Plasma specimens will be collected for the measurement of plasma 5-FU level from patients receiving 5-FU/LV alone, with oxaliplatin (mFOLFOX6) or irinotecan (FOLFIRI), or both (mFOLFOXIRI) chemotherapy. 5-FU doses will be modified based on the assay results.

Who Is Running the Clinical Trial?

Inova Health Care Services

Lead Sponsor

Trials

80

Recruited

22,700+

Findings from Research

The sensitivity to 5-fluorouracil (5-FU) in colorectal cancer patients varies significantly, with individual AUC(IR50) values ranging from less than 100 to over 1000 microg hr/ml, indicating that some patients may respond poorly to this treatment.

Achieving the individual AUC(IR50) is associated with significantly better relapse-free survival, suggesting that personalized chemotherapy duration based on 5-FU sensitivity could enhance treatment outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Study to predict optimal duration of chemotherapy with fluoropyrimidine by multi-point collagen gel droplet embedded drug sensitivity test. Tokunaga, Y., Sasaki, H., Ohnishi, T.[2013]

In a study of 1033 colorectal cancer patients treated with 5-fluorouracil (5FU) based adjuvant therapy, certain adverse events like neutropenia, nausea/vomiting, and mucositis were linked to better disease-free survival (DFS) and overall survival (OS).

Patients who experienced any grade of neutropenia had a 19% lower risk of disease progression, while those with nausea/vomiting had a 38% lower risk of death, suggesting that these adverse effects may serve as positive indicators of treatment response.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Association of adverse events and survival in colorectal cancer patients treated with adjuvant 5-fluorouracil and leucovorin: Is efficacy an impact of toxicity? Soveri, LM., Hermunen, K., de Gramont, A., et al.[2014]

References

1. Netherlands pubmed.ncbi.nlm.nih.gov

Inherited variability in a master regulator polymorphism (rs4846126) associates with survival in 5-FU treated colorectal cancer patients. [2015]

2. Greece pubmed.ncbi.nlm.nih.gov

Study to predict optimal duration of chemotherapy with fluoropyrimidine by multi-point collagen gel droplet embedded drug sensitivity test. [2013]

3. United States pubmed.ncbi.nlm.nih.gov

Development of novel miR-129 mimics with enhanced efficacy to eliminate chemoresistant colon cancer stem cells. [2022]

4. Netherlands pubmed.ncbi.nlm.nih.gov

Pharmacogenomics of 5-fluorouracil in colorectal cancer: review and update. [2021]

5. United Arab Emirates pubmed.ncbi.nlm.nih.gov

Sulfonamide-Functionalized Polymeric Nanoparticles for Enhanced In Vivo Colorectal Cancer Therapy. [2022]

6. England pubmed.ncbi.nlm.nih.gov

Association of adverse events and survival in colorectal cancer patients treated with adjuvant 5-fluorouracil and leucovorin: Is efficacy an impact of toxicity? [2014]

7. France pubmed.ncbi.nlm.nih.gov

Neutrophil elastase inhibitor (MPH-966) improves intestinal mucosal damage and gut microbiota in a mouse model of 5-fluorouracil-induced intestinal mucositis. [2021]

8. England pubmed.ncbi.nlm.nih.gov

Case report on 5-fluorouracil induced cerebrovascular accident. [2021]

9. United States pubmed.ncbi.nlm.nih.gov

5-fluorouracil-induced small bowel toxicity in patients with colorectal carcinoma. [2019]

10. Germany pubmed.ncbi.nlm.nih.gov

The association of polymorphisms in folate-metabolizing genes with response to adjuvant chemotherapy of colorectal cancer. [2019]