#1 Clinical Trials Search in Europe

Tipiracil

Tipiracil, often used in combination with trifluridine, is being extensively studied in clinical trials for the treatment of metastatic colorectal cancer (mCRC). This article examines various clinical trials investigating the efficacy, safety, and potential applications of tipiracil-containing regimens in different treatment settings for colorectal cancer patients.

Table of Contents

What is TIPIRACIL?

TIPIRACIL is a component of an anticancer medication that is often used in combination with another drug called trifluridine. This combination is known by several names, including:

  • Trifluridine/Tipiracil
  • FTD/TPI
  • TAS-102
  • Lonsurf
These names refer to the same medication, which is designed to treat certain types of advanced cancers[1][2].

How TIPIRACIL Works

TIPIRACIL works in partnership with trifluridine to fight cancer cells. Here’s a simplified explanation of how this combination functions:

  1. Trifluridine is the active cancer-fighting component. It gets incorporated into the DNA of cancer cells, which interferes with their ability to grow and divide.
  2. TIPIRACIL (tipiracil hydrochloride) acts as a helper. It prevents the rapid breakdown of trifluridine in the body, allowing it to remain active and effective for a longer period.
This teamwork between the two drugs helps maintain adequate levels of the active cancer-fighting agent in the patient’s body, enhancing its ability to combat cancer cells[3].

Conditions Treated with TIPIRACIL

TIPIRACIL, in combination with trifluridine, is primarily used to treat:

  • Metastatic Colorectal Cancer (mCRC): This is cancer that started in the colon or rectum and has spread to other parts of the body. TIPIRACIL is typically used when other standard treatments have not been effective[4].
  • Cholangiocarcinoma (Bile Duct Cancer): Some clinical trials are exploring the use of TIPIRACIL for this type of cancer that affects the bile ducts[3].
It’s important to note that TIPIRACIL is often used as a later line of treatment, meaning it’s typically given after other treatments have been tried and have not been successful[2].

How TIPIRACIL is Administered

TIPIRACIL, in combination with trifluridine, is usually given as follows:

  • It comes in the form of oral tablets.
  • The medication is typically taken twice daily, within one hour after morning and evening meals.
  • The usual schedule is 5 days on, 2 days off, for 2 weeks, followed by a 14-day rest period.
  • This 28-day cycle is then repeated.
The exact dosage and schedule may vary depending on the patient’s body surface area, overall health, and response to treatment[4][5].

TIPIRACIL in Clinical Trials

TIPIRACIL is being studied in various clinical trials to explore its effectiveness in different scenarios:

  • Combination Therapies: Some trials are investigating TIPIRACIL in combination with other cancer drugs like oxaliplatin, bevacizumab, or irinotecan[6][7].
  • Earlier Treatment Lines: While TIPIRACIL is often used in later stages of treatment, some studies are exploring its use in earlier treatment lines for metastatic colorectal cancer[6].
  • Different Cancer Types: Research is ongoing to determine if TIPIRACIL could be effective in treating other types of cancers beyond colorectal cancer[3].
These clinical trials aim to find new ways to use TIPIRACIL more effectively and potentially help more patients.

Potential Side Effects

Like all medications, TIPIRACIL can cause side effects. Common side effects may include:

  • Decreased blood cell counts (which can lead to increased risk of infection, anemia, or bleeding)
  • Fatigue
  • Nausea or vomiting
  • Diarrhea
  • Loss of appetite
Your healthcare team will monitor you closely for these and other potential side effects. They may adjust your dosage or provide supportive care to manage these effects[2].

Impact on Quality of Life

Many clinical trials studying TIPIRACIL also assess its impact on patients’ quality of life. This is typically done using standardized questionnaires that evaluate various aspects of a patient’s well-being, including:

  • Physical functioning
  • Emotional state
  • Ability to perform daily activities
  • Overall health status
These assessments help researchers and healthcare providers understand how the treatment affects patients’ daily lives beyond just controlling the cancer. This information is crucial in determining the overall benefit of the treatment[4][2].

Aspect Details
Primary Use Treatment of metastatic colorectal cancer (mCRC)
Mechanism of Action Trifluridine incorporates into DNA for anti-tumor effects; Tipiracil prevents rapid degradation of trifluridine
Common Combinations With oxaliplatin, bevacizumab, irinotecan, anti-EGFR antibodies
Key Efficacy Measures Overall Survival (OS), Progression-Free Survival (PFS), Disease Control Rate (DCR), Objective Response Rate (ORR)
Safety Assessment Adverse Events (AEs) graded by CTCAE, laboratory values monitoring
Quality of Life Measures PRO-CTCAE, EQ-5D-5L questionnaires
Ongoing Research First-line treatment, combination therapies, real-world effectiveness

FAQ

  • What is the primary use of tipiracil in colorectal cancer treatment? Tipiracil, typically used in combination with trifluridine (as trifluridine/tipiracil), is primarily used in the treatment of metastatic colorectal cancer (mCRC), especially in patients who have been previously treated with or are not considered candidates for available therapies.
  • How does trifluridine/tipiracil work? Trifluridine/tipiracil is an oral combination medication. Trifluridine is the active cytotoxic component that gets incorporated into DNA, resulting in anti-tumor effects. Tipiracil hydrochloride inhibits thymidine phosphorylase, preventing the rapid degradation of trifluridine and maintaining adequate plasma levels of the active drug.
  • What are some common side effects of trifluridine/tipiracil? Common side effects of trifluridine/tipiracil may include neutropenia (low white blood cell count), anemia, fatigue, nausea, and decreased appetite. The safety profile is typically assessed using the Common Terminology Criteria for Adverse Events (CTCAE).
  • Is trifluridine/tipiracil being studied in combination with other treatments? Yes, several clinical trials are investigating trifluridine/tipiracil in combination with other treatments. For example, it's being studied in combination with oxaliplatin and bevacizumab, as well as with anti-EGFR antibodies like futuximab/modotuximab.
  • How is the effectiveness of trifluridine/tipiracil measured in clinical trials? The effectiveness of trifluridine/tipiracil is typically measured using endpoints such as overall survival (OS), progression-free survival (PFS), disease control rate (DCR), and objective response rate (ORR). Quality of life measures are also often included in these studies.

Ongoing Clinical Trials on Tipiracil

  • Study of melphalan followed by trifluridine-tipiracil and bevacizumab combination versus trifluridine-tipiracil and bevacizumab in liver metastatic colorectal cancer

    Recruiting

    1 1 1
    Investigated diseases:
    Investigated drugs:
    Czechia Germany Italy The Netherlands Spain

  • Study on the Safety of Trifluridine/Tipiracil for Patients with Dihydropyrimidine Dehydrogenase Deficiency and Metastatic Colorectal or Gastroesophageal Cancer

    Recruiting

    1 1 1
    Investigated diseases:
    Investigated drugs:
    France

  • Study of Oxaliplatin, Nivolumab, and Trifluridine/Tipiracil for Patients with Advanced Gastric, Esophageal, or Gastroesophageal Junction Cancer

    Recruiting

    1 1 1
    Investigated diseases:
    Investigated drugs:
    France

  • Study on the Effectiveness of Chemotherapy with Folinic Acid, Fluorouracil, and Irinotecan for Patients with Stage III Colon Cancer After Surgery

    Recruiting

    1 1 1 1
    Investigated drugs:
    France

  • Study on the Effectiveness and Safety of AZD0901 Compared to Standard Treatments for Adults with Advanced Gastric or Gastroesophageal Junction Cancer Expressing Claudin 18.2

    Not recruiting

    1 1 1 1
    Investigated diseases:
    Investigated drugs:
    France Germany Italy Poland Spain

  • Study Comparing Sacituzumab Govitecan with Standard Treatment for Patients with Metastatic Colorectal Cancer

    Not recruiting

    1 1 1 1
    Investigated diseases:
    Investigated drugs:
    Germany

  • Study of MK-4280A (Favezelimab and Pembrolizumab) for Patients with Metastatic Colorectal Cancer After Previous Treatment

    Not recruiting

    1 1 1 1
    Investigated drugs:
    France Italy Norway Spain

  • Study on Botensilimab Alone and with Balstilimab or Drug Combination for Patients with Refractory Metastatic Colorectal Cancer

    Not recruiting

    1 1 1
    Investigated diseases:
    Investigated drugs:
    Belgium France Italy Spain

Glossary

  • Metastatic Colorectal Cancer (mCRC): A type of colorectal cancer that has spread from the colon or rectum to other parts of the body.
  • Trifluridine/Tipiracil: An oral combination drug used in the treatment of metastatic colorectal cancer, consisting of trifluridine (a nucleoside metabolic inhibitor) and tipiracil (a thymidine phosphorylase inhibitor).
  • Overall Survival (OS): The length of time from either the date of diagnosis or the start of treatment for a disease that patients are still alive.
  • Progression-Free Survival (PFS): The length of time during and after the treatment of a disease that a patient lives with the disease but it does not get worse.
  • Disease Control Rate (DCR): The percentage of patients with advanced or metastatic cancer who have achieved complete response, partial response, and stable disease to a therapeutic intervention.
  • Objective Response Rate (ORR): The proportion of patients whose cancer shrinks or disappears after treatment.
  • RECIST: Response Evaluation Criteria in Solid Tumors, a set of rules used to measure a cancer patient's response to treatment.
  • CTCAE: Common Terminology Criteria for Adverse Events, a set of criteria for the standardized classification of adverse effects of drugs used in cancer therapy.
  • Quality of Life (QoL): A measure of an individual's perceived physical and mental health over time.
  • Bevacizumab: A cancer medication that interferes with the growth of blood vessels that support tumor growth.

References

  1. https://clinicaltrials.gov/study/NCT04965870
  2. https://clinicaltrials.gov/study/NCT03665506
  3. https://clinicaltrials.gov/study/NCT04076761
  4. https://clinicaltrials.gov/study/NCT04450836
  5. https://clinicaltrials.gov/study/NCT05223673
  6. https://clinicaltrials.gov/study/NCT05077839
  7. https://clinicaltrials.gov/study/NCT06242067