Some response to raltitrexed seen in malignant pleural mesothelioma

NEW YORK (Reuters Health) - Raltitrexed is active as a single agent in the treatment of malignant pleural mesothelioma (MPM), results of a study published in the February issue of the European Journal of Cancer indicate.

Raltitrexed (Tomudex; AstraZeneca) is a quinazoline folate analog that specifically inhibits thymidylate synthase, "which is one of three enzymes involved in the synthesis of DNA, note Dr. P. Baas, of the Netherlands Cancer Institute, Amsterdam, and colleagues with the European Organization for Research and Treatment of Cancer (EORTC).

The researchers examined the activity and toxicity of raltitrexed in the treatment of 25 chemo-naïve patients with MPM in an open-label study.

The patients received 3 mg/m² intravenous bolus of raltitrexed every 3 weeks. The mean number of cycles administered was 3, with a range from 1 to 8. Overall, 24 subjects received 104 cycles.

Five patients (20.8%) achieved a partial response. This was confirmed by an independent radiology committee. "The mean duration of response was 9.4 months, the median survival of the whole group was 7 months," Dr. Baas and colleagues report.

The team reports that toxicity was mild and did not exceed grade 3. Major adverse events included diarrhea, nausea, vomiting, fatigue, and neutropenia.

A trial involving raltitrexed combined with cisplatin is nearing completion, the investigators note. "This trial should further clarify the role of raltitrexed and antifolates in the treatment of MPM and help us in determining the 'optimal' chemotherapy treatment in this disease."