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) decreases dyspnea in patients with malignant pleural mesothelioma (MPM). Therapy with Platinol alone also had this effect. The details of this randomized phase III trial evaluating quality of life parameters were reported in the March 20, 2006, 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, 25 patients with untreated MPM were randomly allocated to receive treatment with Platinol alone or Platinol plus Tomudex. The details of response and survival were reported last year in the Journal of Clinical Oncology and summarized below in Related News.[3] Essentially this study showed that the addition of Tomudex improved the response from 13% to 23.6% and prolonged median survival from 8.8 months to 11.4 months.

The current analyses report short term treatment-related complications and quality of life results. Assessments were made at baseline, after each treatment cycle, at the end of treatment and every 6 weeks for 6 months. This analysis confirmed the survival benefit of combination therapy reported in the original trial. This study did not find major differences in quality of life parameters between patients receiving Platinol alone or Platinol plus Tomudex. However, they did report that patients receiving either therapy had improvement in dyspnea after cycle 2 of therapy.

Comments: This study suggests that both therapies improve quality of life to the same degree. However, combination chemotherapy would be preferable since survival is improved.

Related News:

The Combination Oxaliplatin and Raltitrexed is Effective For Treatment of Inoperable Malignant Pleural Mesothelioma: Results of a Pilot Study(5/14/2002)

Alimta® Approved for Mesothelioma(2/5/2004)

Pemexetred (Altima®) plus Platinol® Extends Survival in Mesothelioma: First Therapy to Make a Difference (7/14/2003)

References