What is Raltitrexed?

Raltitrexed was developed in England in the 1980s by professor and chemist Ken Harrap.

Harrap also developed carboplatin, the alternative to cisplatin that causes fewer side effects.

In the 1990s, raltitrexed was approved in the U.K. and Europe as an alternative to 5-fluorouracil in the treatment of colorectal cancer. It is available in 40 countries, but not in the U.S.

Raltitrexed is primarily used as a palliative treatment for advanced colorectal cancer. It has also been used to treat mesothelioma, stomach (gastric) cancer, pancreatic cancer, head and neck cancer and non-small cell lung cancer.

Raltitrexed seems to work best against mesothelioma when combined with cisplatin. A 2021 research study noted that raltitrexed demonstrated improved survival in combination with cisplatin in patients with epithelioid type mesothelioma.

However, the results are not as good as the combination of cisplatin and pemetrexed (Alitma) — the most common chemotherapy drugs used for treating mesothelioma.

How Does Raltitrexed Work?

Raltitrexed works by disrupting the way cancer cells grow. It damages the DNA of cancer cells and causes them to die.

Raltitrexed is part of the antimetabolite group of cancer drugs. Antimetabolite is a medical term for drugs that block normal metabolism inside cells.

These drugs interfere with DNA replication, which is the way cells grow and divide to make more cells.

Raltitrexed damages DNA in ways that limit cancer cells from multiplying. This is how raltitrexed slows tumor growth.

Raltitrexed Information
Name: Tomudex
Alternate Names: Raltitrexed, raltitrexed disodium
Manufacturer: AstraZeneca
Dosage: 3 mg
Administration Route: Intravenous
Active Ingredient: Raltitrexed
Drug Class: Antimetabolite
Medical Code: None
Interacting Drug: Folic acid, warfarin, NSAIDs
Medical Studies: Cisplatin With or Without Raltitrexed in Treating Patients With Malignant Mesothelioma of the Pleura
FDA Warning: Not approved by the FDA

Raltitrexed Side Effects

Raltitrexed can harm healthy cells in addition to cancer cells. This harm can cause side effects that range from mild to severe.

Common side effects of raltitrexed include:

  • Fever
  • Fatigue
  • Constipation or diarrhea
  • Indigestion and stomach pain
  • Loss of appetite
  • Skin rash
  • Low blood cell counts
  • Elevated liver enzymes

Some patients also report headaches, mouth sores, hair loss, weight loss, increased sweating, swelling of hands and feet, muscle cramps and joint pain. Patients are also at an increased risk of getting an eye infection.

Tell your doctor if you develop any side effects right away. They can prescribe medication to control your side effects. They may also reduce your dose of raltitrexed until your side effects weaken.

Raltitrexed Warnings

Other drugs that negatively interact with raltitrexed include:

  • Folic acid
  • NSAIDs such as ibuprofen
  • Warfarin

The U.S. Food and Drug Administration has not reviewed raltitrexed for approval or issued any warnings for its use. But, other international health agencies have issued warnings and contraindications.

For example, patients with kidney, liver or heart problems should not take raltitrexed. Women who are pregnant or breastfeeding should not take the drug.

Raltitrexed is also known to make cancer cells more sensitive to radiation therapy. For this reason, doctors are careful when they combine raltitrexed with radiation therapy.

Research on Raltitrexed in Mesothelioma Treatment

Raltitrexed can kill mesothelioma cells as a singular therapy. But, it is more effective when combined with other chemotherapy drugs.

Most of the research involves a combination of raltitrexed with a platinum-based drug such as cisplatin.

In 2005, researchers from Europe and Canada published results from a phase III clinical trial of raltitrexed and cisplatin in 213 pleural mesothelioma patients.

Raltitrexed and Cisplatin Study Results:

  • A total of 23.6% of participants responded to the drug combination.
  • The median survival time was 11.4 months.
  • One-year survival was 46%.

While these results are better than no treatment, they aren’t as good as the results achieved with cisplatin and pemetrexed.

Results of Cisplatin and Pemetrexed Combination:

  • Around 41% of pleural patients respond to cisplatin and pemetrexed.
  • The median survival time is about 12.1 months.
  • One-year survival is around 58%.

Mixed results have come from other mesothelioma clinical trials where raltitrexed was combined with another chemotherapy drug.

For example, raltitrexed and oxaliplatin has a low response rate and median survival ranges from 14 weeks to 44 weeks. Oxaliplatin is a third-generation platinum drug that is like cisplatin.

While raltitrexed is not available in the U.S., other countries use raltitrexed interchangeably with pemetrexed.

These countries include Canada, Mexico, the United Kingdom and European nations. Many U.K. doctors recommend raltitrexed instead of pemetrexed because raltitrexed is less expensive.

Canadian researchers used raltitrexed or pemetrexed in the SMART trial, which applied radiation therapy before surgery and chemotherapy.

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