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.
References
Choi, Y. J. et al. Phase II study of pemetrexed in combination with cisplatin in patients with advanced urothelial cancer: the PECULIAR study (KCSG 10-17). Br. J. Cancer 10.1038/bjc.2014.591
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Phillips, R. PECULIAR, but promising. Nat Rev Urol 12, 2 (2015). https://doi.org/10.1038/nrurol.2014.342
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DOI: https://doi.org/10.1038/nrurol.2014.342