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Tomudex® Plus Platinol® Improves Survival of Patients with Malignant Pleural Mesothelioma
October 3, 2005
Source: CancerConsultants.com

Researchers affiliated with the European Organization for Research and Treatment of Cancer (EORTC) Lung Cancer Group and the National Cancer Institute of Canada have reported that the combination of Tomudex (raltitrexed) and Platinol (cisplatin) improves survival of patients with malignant pleural mesothelioma (MPM) compared to Platinol alone. The details of this randomized phase III trial were reported in the October 1, 2005, issue of the Journal of Clinical Oncology .[1]

Malignant pleural mesothelioma is a rare cancer caused by chronic exposure to asbestos. Patients with this disease often have a decreased quality of life from symptoms caused by the cancer, such as shortness of breath, cough, pain, fatigue, and the inability to eat. This type of cancer is resistant to most therapies, which consist of surgery, chemotherapy, and/or radiation therapy. Furthermore, most people do not learn they have malignant pleural mesothelioma until the disease has progressed to an advanced stage when treatment with surgery or radiation is not an option. Therefore, identification of a chemotherapy regimen that can improve quality of life or survival is essential for improving care in this population.

Mesothelioma is regarded as relatively chemo-resistant, but recent studies have shown that significant palliation is possible with newer chemotherapy approaches. Platinol alone has been the standard by which other regimens are judged. However, there is emerging evidence that combining an anti-metabolite with a platinum compound may now be the current best approach to treating patients with MPM.

The anti-metabolite that has been studied the most is Alimta® (pemetrexed) which has been combined with Platinol producing results superior to Platinol alone. Tomudex is another anti-metabolite that is approved in Europe and Canada for use in the treatment of colon cancer. Tomudex is a prodrug that is converted to polyglutamates, which inhibit thymidylate synthase. Single agent Tomudex has demonstrated activity in the treatment of MPM.[2]

In the current trial, 257 patients with untreated MPM were randomly allocated to receive treatment with Platinol alone or Platinol plus Tomudex.

Table 1: Platinol plus Tomudex versus Platinol alone in untreated MPM patients

These authors stated that they did not observe the myelosuppression previously observed with Alimta, which necessitates the administration of folic acid and vitamin B12.

Comments: Alimta and Tomudex are two new antifolates that interfer with pyrimidine metabolism. One advantage to Tomudex over Alimta is that it does not appear to require supplementation with folic acid and vitamin B12 to prevent toxicity. Alimta in combination with Platinol was approved by the U.S. Food and Drug Administration in February 2004 for the treatment of MPM. Thus, combining an anti-metabolite with Platinol would currently require the use of Alimta in the United States where Tomudex is not an approved drug.

References

[1} Van Meerbeeck JP, Gaafar R, Manegold C, et al. Randomized phase III study of cisplatin with or without raltitrexed in patients with malignant pleural mesothelioma: an intergroup study of the European Organisation for Reserch and Treatment of Cancer Lung Cancer Group and the National Cancer Institute of Canada. Journal of Clinical Oncology. 2005;23:6881-6889.

[2] Baas P, ardizzoni A, Grossi F, et al. EORTC Lung Cancer Group: The activity of raltitrexed (Tomudex) in malignant pleural mesothelioma: An EORTC phase II study (08992). European Journal of Cancer . 2003;39:353-357.