New molecular targets and novel agents in the treatment of advanced urothelial cancer.
Standard cytotoxic regimens for metastatic bladder cancer, such as gemcitabine/cisplatin or methotrexate, vinblastine, doxorubicin, and cipslatin (M-VAC), yield impressive overall response rates of 45% to 70%. Despite this, long-term, disease-free, overall survival is rare, and most patients eventually succumb to the disease. Much work has been undertaken evaluating the clinical and molecular factors associated with progressive bladder cancer, and this has, in turn, led to the development of both novel targets and agents. These include standard cytotoxics such as pemetrexed, an antifolate and antimetabolite agent that has demonstrated an overall response rate of 30% in early studies, and small-molecule tyrosine kinase inhibitors such as sunitinib, which will be studied as maintenance therapy for patients who respond to first-line chemotherapy. The evaluation of new targets and new agents in the midst of limited patient, logistical, and financial resources will be one of the more difficult challenges for investigators over the next several years.
Beekman
Kathleen W
KW
Genitourinary Oncology Service, Division of Hematology-Oncology, Department of Internal Medicine, University of Michigan, Ann Arbor, MI, USA. katew@umich.edu
Bradley
Deborah
D
Hussain
Maha
M
D020533:Angiogenesis Inhibitors / Q000627:therapeutic use; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D002453:Cell Cycle / Q000187:drug effects; D016503:Drug Delivery Systems; D056572:Histone Deacetylase Inhibitors; D006801:Humans; D009944:Organoplatinum Compounds / Q000627:therapeutic use; D050257:Tubulin Modulators / Q000627:therapeutic use; D001749:Urinary Bladder Neoplasms / Q000188:drug therapy*; D042461:Vascular Endothelial Growth Factor A / Q000037:antagonists & inhibitors
D020533:Angiogenesis Inhibitors; D000970:Antineoplastic Agents; D056572:Histone Deacetylase Inhibitors; D009944:Organoplatinum Compounds; D050257:Tubulin Modulators; D042461:Vascular Endothelial Growth Factor A; C081294:satraplatin