Raltitrexed: current clinical status and future directions

Our plain-English summary of Raltitrexed: current clinical status and future directions, by E. Van Cutsem, D. Cunningham, J. Maroun, et al (Annals of Oncology, 2002).

The study

• Authors: E. Van Cutsem, D. Cunningham, J. Maroun, A. Cervantes, B. Glimelius
• Journal: Annals of Oncology
• Published: 2002;13(4):513-22
• Type of article: Review
• Cited by: 66 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

Raltitrexed ('Tomudex') monotherapy is a conveniently administered alternative to 5-fluorouracil (5-FU) in the first-line treatment of advanced colorectal cancer (CRC), and has single-agent activity in a variety of advanced solid tumours. Although both raltitrexed and 5-FU are thymidylate synthase inhibitors, raltitrexed has a specific mode of action and a toxicity profile distinct from 5-FU. The mechanism of action of raltitrexed is also completely different from that of oxaliplatin, irinotecan and other drugs with which it has been combined. These properties, together with preclinical data, suggested that combinations of raltitrexed with 5-FU, other chemotherapeutic agents, or radiotherapy could result in improved therapies for a variety of advanced solid tumours, including advanced CRC. This review outlines the appropriate management of patients treated with raltitrexed, whether as monotherapy or in combination, and discusses the preliminary results of combination studies with raltitrexed in a range of tumour types including advanced CRC, malignant mesothelioma, gastric, pancreatic, head and neck, and non-small-cell lung cancers. Of particular interest is the combination of raltitrexed and oxaliplatin, which has shown promising antitumour effects in first-line treatment of advanced CRC and malignant mesothelioma, a disease that is refractory to chemotherapy.

In plain English

This article was a review, not a new study. The authors summarised earlier and preliminary trial results for raltitrexed ('Tomudex'), a chemotherapy drug. It was given alone, with other drugs, or with radiotherapy, mainly in advanced colorectal cancer but also in malignant mesothelioma and several other cancers. The article did not study asbestos exposure. In an earlier phase I trial of raltitrexed with oxaliplatin, 35% of 17 patients with malignant mesothelioma (95% confidence interval 14% to 59%) had a partial response. Preliminary results of a later phase II trial showed a response rate of 25% (95% confidence interval 15% to 37%) among 56 evaluable patients. In that trial, median survival of patients not previously given chemotherapy was 189 days (95% confidence interval 147 to 222 days) from the start of treatment. A phase III trial comparing raltitrexed plus cisplatin with cisplatin alone in mesothelioma was described as ongoing. The review also gave dose-reduction rules for patients with reduced kidney function or side effects. The authors noted that the combination studies were relatively small. They concluded that promising results had been obtained, especially in malignant mesothelioma.

We wrote this plain-English summary from the full article with the help of AI, and a second AI model checked each sentence against the article. It is not the authors' wording; the abstract and the article are their own account.

What the study did and found

• Design: Review of clinical trials of raltitrexed as monotherapy and in combination therapy
• Who was studied: No study population of its own. The review covered phase I, II and III trials, many reported as conference abstracts or preliminary results. Patients in these trials had advanced colorectal cancer, malignant mesothelioma, non-small-cell lung cancer, or gastric, pancreatic or head and neck cancers.
• Exposure: No asbestos exposure was studied. The treatment reviewed was raltitrexed, given alone or combined with 5-FU, oxaliplatin, irinotecan, cisplatin, doxorubicin, gemcitabine or radiotherapy.
• Main results:
  • In a cited phase I trial of raltitrexed plus oxaliplatin, patients with malignant mesothelioma had a response rate of 35% (95% CI 14% to 59%) of 17 patients.
  • In a cited phase II trial of raltitrexed plus oxaliplatin in malignant mesothelioma, which entered 72 patients, the response rate was 25% (95% CI 15% to 37%) among 56 evaluable patients.
  • In that phase II mesothelioma trial, median survival of patients not previously given chemotherapy was 189 days (95% CI 147 to 222 days) from the start of treatment. Measured from diagnosis, it was 309 days (95% CI 259 to 439 days).
  • A phase III study by the European Organisation for Research and Treatment of Cancer was ongoing at the time of the review. It compared raltitrexed plus cisplatin with cisplatin alone in malignant mesothelioma.
  • Two cited phase II studies gave raltitrexed plus oxaliplatin as first treatment for advanced colorectal cancer. Their response rates were 60% (47% to 71%) and 46% (31% to 61%).
  • In the large phase III colorectal cancer trials, treatment-related deaths were 3.8% with raltitrexed compared with 2.6% with 5-FU–LV. When patients not treated according to the prescribing information were excluded, the figures were 1.3% with raltitrexed and 1.7% with bolus 5-FU–LV.
• The authors' conclusion: The authors concluded that raltitrexed combination chemotherapy had given promising results in advanced colorectal cancer and other advanced solid tumours, especially malignant mesothelioma. They said ongoing studies should further establish its role.
• Limitations the authors state:
  • The authors described the phase I and II combination studies they reviewed as relatively small.

Topics

The National Library of Medicine indexes this study under subjects our site covers: Colon cancer, Mesothelioma.

Medical terms in this study, explained in our Lexicon: Raltitrexed, Fluorouracil (5-FU), Colorectal Cancer, Malignant Mesothelioma, Lung Cancer, Chemotherapy.

Related studies

• Raltitrexed in mesothelioma — V.F. Surmont, J.P. van Meerbeeck (2011)
• Raltitrexed Inhibits HepG2 Cell Proliferation via G0/G1 Cell Cycle Arrest — H. Zhao, Y. Zhang, et al. (2016)
• Phase I, dose-finding, and pharmacokinetic study of raltitrexed combined with oxaliplatin in patients with advanced cancer — K. Fizazi, M. Ducreux, et al. (2000)
• Oxaliplatin and raltitrexed in the treatment of inoperable malignant pleural mesothelioma: results of a pilot study — R. Maisano, N. Caristi, et al. (2001)
• Combination raltitrexed (Tomudex(R))-oxaliplatin: a step forward in the struggle against mesothelioma? The Institut Gustave Roussy experience with chemotherapy and chemo-immunotherapy in mesothelioma — K. Fizazi, R. Caliandro, et al. (2000)
• Thymidylate synthase: a critical target for cancer chemotherapy — M.G. Rose, M.P. Farrell, et al. (2002)

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