Alimta is supported by several studies for bladder cancer. A study presented at the Chemotherapy Foundation Symposium XXI showed that Alimta® appears to be an active single agent in the second-line treatment of transitional cell carcinoma (TCC) of the urothelium. Results indicate that more than one quarter of patients responded to the drug. This phase II study involved 47 patients with metastatic TCC, all of whom had only one prior treatment for metastatic disease, or relapsed within one year of adjuvant therapy. Alimta® was administered as a 10-minute intravenous infusion at 500 mg/m2 every 21 days. Patients also received dexamethasone, 4 mg po bid on the day before, day of, and day after infusion to reduce the skin-associated drug rash. Daily folic acid (400 mg) and vitamin B12 (1000 mg) were administered intramuscularly every nine weeks beginning one to two weeks before the first Alimta® dose. There were 13 confirmed responses, three of which were complete, 10 were partial for an overall response rate of 27%. The median time to disease progression was 2.4 months and the median overall survival was 9.8 months. Approximately 35% of patients are alive at 12 months. Alimta® is an active single agent in patients with TCC of the urothelium who have a creatinine clearance greater than 45 mL/min. The regimen is well-tolerated, provided the appropriate vitamin supplementation is administered. This trial certainly prompts further study of Alimta® in combination with other agents to determine if its activity can be enhanced. Such trials are now ongoing.
NCCN BL-G says that there are no standard options for second line therapy and recommends clincal trials. It lists palliative options: amongst them, cisplatina, carboplatin, docetaxel, doxorubicin, 5FU, gemcitabine, ifosfamide, paclitaxel, premetrexed(Alimta), methotrexate and vinblastine.
NCCN.ORG, Bladder cancer
Matthew D. Galsky, Svetlana Mironov, Alexia Iasonos, Joseph Scattergood, Mary G. Boyle and Dean F. Bajorin Phase II trial of pemetrexed as second-line therapy in patients with metastatic urothelial carcinoma Investigational New Drugs Volume 25, Number 3,
Sweeney C, Roth BJ, Kaufman DS, et al. Phase II study of pemetrexed (PEM) for second-line treatment of transitional cell cancer (TCC) of the bladder. Proc Am Soc Clin Oncol 2003;22,411 Abstract 1653.
Sweeney CJ, Roth BJ, Kabbinavar FF, et al. Phase II study of pemetrexed for second-line treatment of transitional cell cancer of the urothelium. J Clin Oncol. 2006;24(21):3451-3457. Marin M. Clinical experience with pemetrexed in breast cancer. Semin Oncol. 2006;33(1 Suppl 2):S15-S18. Pagliaro LC, Sharma P. Review of metastatic bladder cancer. Minerva Urol Nefrol. 2006;58(1):53-71. Bellmunt J, Albiol S. Chemotherapy for metastatic or unresectable bladder cancer. Semin Oncol. 2007;34(2):135-144.