Phase II open-label study of oral piritrexim in patients with advanced carcinoma of the urothelium who have experienced failure with standard chemotherapy.

Background: Piritrexim is reported to have a response rate of 38% in patients with chemotherapy-naive disease and 23% for second-line therapy after chemotherapy failure. We report the results of a multiinstitutional, open-label, 2-stage, phase II study that further evaluates oral piritrexim in patients with urothelial carcinoma and who proved nonresponsive to standard chemotherapy.

Patients And Methods: Eligible patients included those with bi-dimensionally measurable disease and an Eastern Cooperative Oncology Group performance status of 0-2, transitional cell carcinoma or adenocarcinoma of the urothelium, and nonresponse to > or = 1 previous standard chemotherapy regimen.

Endothelin receptor antagonists in the treatment of prostate cancer.

The endothelin (ET) axis represents a novel and exciting target in the treatment of prostate cancer. ET-1, acting primarily through the endothelin A receptor (ET(A)), is integrally involved in multiple facets of prostate cancer progression, including cell growth, inhibition of apoptosis, angiogenesis, development and progression of bone metastases, and mediation of pain responses. Clinical trials with the ET(A) antagonist, atrasentan, have demonstrated good tolerability, with the most common adverse events being headache, rhinitis, and peripheral edema.

The dilemma of patients with a rising PSA level after definitive local therapy for prostate cancer.

Patients with a rising prostate-specific antigen (PSA) levels after definitive local therapy now represent one of the largest and fastest growing groups of men with prostate cancer. The great majority of these men are asymptomatic with no other evidence of disease, and their clinical outcomes have been widely variable and poorly understood. Recently, several groups have analyzed their institutions' data and reported on certain pathologic and clinical variables that have increased our understanding of the natural history of these men, and to some extent allowed for the development of predictive models to aid in deciding who should be treated more aggressively and who should be watched.