Raltitrexed was developed in England in the 1980s by professor and chemist Ken Harrap.
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.
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.
|Alternate Names||Raltitrexed, raltitrexed disodium|
|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|
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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:
- 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.
Other drugs that negatively interact with raltitrexed include:
- Folic acid
- NSAIDs such as ibuprofen
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 percent of participants responded to the drug combination.
- The median survival time was 11.4 months.
- One-year survival was 46 percent.
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 percent of pleural patients respond to cisplatin and pemetrexed.
- The median survival time is about 12.1 months.
- One-year survival is around 58 percent.
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.
14 Cited Article Sources
BCCA Cancer Drug Manual. (2013, June 1). Raltitrexed.
Retrieved from: http://www.bccancer.bc.ca/drug-database-site/Drug%20Index/Raltitrexed_monograph_1June2013_formatted.pdf
Workman, P. (2017, February 15). A pioneer of cancer drug discovery – Professor Ken Harrap 1931-2017.
Retrieved from: https://www.icr.ac.uk/blogs/the-drug-discoverer/page-details/a-pioneer-of-cancer-drug-discovery-professor-ken-harrap-1931-2017
Cancer Research UK. (2015, April 29). Raltitrexed (Tomudex).
Retrieved from: http://www.cancerresearchuk.org/about-cancer/cancer-in-general/treatment/cancer-drugs/drugs/raltitrexed
Cancer Research UK. (2015, April 29). Side effects of raltitrexed (Tomudex).
Retrieved from: http://www.cancerresearchuk.org/about-cancer/cancer-in-general/treatment/cancer-drugs/drugs/raltitrexed/side-effects
Van Cutsem, E. et al. (2002). Raltitrexed: current clinical status and future directions.
Retrieved from: https://academic.oup.com/annonc/article/13/4/513/212160
Van Meerbeeck, J.P. et al. (2005). Randomized phase III study of cisplatin with or without raltitrexed in patients with malignant pleural mesothelioma: an intergroup study of the European Organisation for Research and Treatment of Cancer Lung Cancer Group and the National Cancer Institute of Canada.
Retrieved from: https://www.ncbi.nlm.nih.gov/pubmed/16192580
Ak, G. et al. (2015). The effectiveness and safety of platinum-based pemetrexed and platinum-based gemcitabine treatment in patients with malignant pleural mesothelioma.
Retrieved from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4496921/
Vogelzang, N.J. et al. (2003). Phase III Study of Pemetrexed in Combination With Cisplatin Versus Cisplatin Alone in Patients With Malignant Pleural Mesothelioma.
Retrieved from: https://www.ncbi.nlm.nih.gov/pubmed/12860938
Fizazi, K. et al. (2003). Combination of raltitrexed and oxaliplatin is an active regimen in malignant mesothelioma: results of a phase II study.
Retrieved from: https://www.ncbi.nlm.nih.gov/pubmed/12525529
Porta, C. et al. (2005). Raltitrexed-Oxaliplatin combination chemotherapy is inactive as second-line treatment for malignant pleural mesothelioma patients.
Retrieved from: https://www.ncbi.nlm.nih.gov/pubmed/15893013
Baas, P. et al. (2003). The activity of raltitrexed (Tomudex) in malignant pleural mesothelioma: An EORTC phase II study.
Retrieved from: https://www.ncbi.nlm.nih.gov/pubmed/12565988
Cho, B.C. et al. (2014). A feasibility study evaluating Surgery for Mesothelioma After Radiation Therapy: the "SMART" approach for resectable malignant pleural mesothelioma.
Retrieved from: https://www.ncbi.nlm.nih.gov/pubmed/24445595/
Clinical Trials. (2017, September 25). Short neoadjuvant hemithoracic IMRT for MPM.
Retrieved from: https://clinicaltrials.gov/show/NCT00797719
- Woods, B. et al. (2012). Raltitrexed plus cisplatin is cost-effective compared with pemetrexed plus cisplatin in patients with malignant pleural mesothelioma. Retrieved from: https://www.ncbi.nlm.nih.gov/pubmed/21937141
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Last Modified September 24, 2018