A combination of cisplatin and the thymidylate synthase inhibitor pemetrexed has been shown to be active in the treatment of advanced urothelial cancer, and provides a convenient and well-tolerated regimen.

Urothelial carcinoma is a highly lethal disease if diagnosed at an advanced stage. Combination chemotherapy is the most effective approach available for this condition, and cisplatin-based combinations are the current first-line treatments. However, as long-term survival is rare and toxicity frequent, improved therapies are required.

Pemetrexed has previously undergone evaluation as a single agent and in combination with gemcitabine for treatment of urothelial carcinoma, with promising results. In a multicentre, single-arm, open-label phase II clinical trial, pemetrexed has now been combined with cisplatin. 42 patients with advanced urothelial carcinoma received 500 mg/m2 pemetrexed with 70 mg/m2 cisplatin every 3 weeks, for a median of eight cycles. 27 patients had partial responses, and seven had stable disease, giving a disease control rate of 81%. Median progression-free survival was 6.9 months, and overall survival was 14.4 months. These values are comparable to those of the current first-line chemotherapy regimens. The new combination has the advantage of convenience, requiring low-dose folic acid and vitamin B1 supplementation, but no mid-cycle chemotherapy. It is also well tolerated, enabling a high dose density of cisplatin.

Phase III trials of this combination are now required, to determine whether early promise translates to superior outcomes.