A Phase II study of oxaliplatin in urothelial cancer.

PURPOSE: To assess the antitumor activity of oxaliplatin, a third generation platinum derivative with a 1,2-diaminocyclohexane (DACH) carrier ligand, in patients with metastatic transitional cell carcinoma of the bladder (TCC). PATIENTS AND METHODS: In a double-arm two-stage Phase II trial, adult patients with previously treated measurable unresectable or metastatic TCC were stratified as "cisplatin-sensitive" or "cisplatin-resistant" based on timing of prior cisplatin treatment and treated with oxaliplatin 130 mg/m2 IV every 3 weeks. The primary endpoint was objective response, and secondary endpoints were duration of response, overall survival, and toxicity. RESULTS: Twenty patients were enrolled between February 2000 and February 2002. A median of two treatment cycles (range, 1-6) were administered. One partial response was observed in 10 cisplatin-sensitive patients, and no responses occurred in eight cisplatin-resistant patients. The most common side effects were fatigue, sensory neuropathy, and nausea. Hematological toxicities were Grade 2 or less. Eleven patients (55%) experienced nonhematological toxicity of Grade 3 or 4, and one patient died of pulmonary embolism after the first cycle. CONCLUSIONS: Minimal antitumor activity of single-agent oxaliplatin was observed in TCC patients previously treated with chemotherapy regardless of time from prior cisplatin exposure.

A randomized Phase II trial of the antiangiogenic agent SU5416 in hormone-refractory prostate cancer.

PURPOSE: To assess the activity of the antiangiogenic agent and VEGFR2 inhibitor SU5416 in hormone-refractory prostate cancer. PATIENTS AND METHODS: Thirty-six chemotherapy naïve patients were randomized to treatment with SU5416 (145 mg/m(2)) and dexamethasone premedication or dexamethasone alone. Patients in the control arm could cross over to experimental therapy after progression. Prostate-specific antigen (PSA) was measured every 2 weeks, and radiological evaluation was performed every 8 weeks. In vitro assessment of SU5416 on PSA secretion was assessed in the LNCaP cell line. Baseline serum basic fibroblast growth factor and plasma vascular endothelial growth factor (VEGF) were explored as prognostic factors. RESULTS: VEGF receptor-2 expression is detectable in prostate cancer cell lines, and SU5416 inhibited in vitro PSA secretion. No effect of SU5416 on PSA secretion or time to progression is detectable in patients. VEGF and basic fibroblast growth factor were not prognostic. Headache and fatigue were the most common SU5416 toxicities, but hyperglycemia, hyponatremia, lymphopenia, infection, and adrenal suppression, all attributable to steroids and the required central line, were common. CONCLUSION: No disease modifying effects of SU5416 were detectable in this small study. Modest toxicity, an inconvenient administration schedule, and availability of other VEGFR-targeted agents support the decision to halt further evaluation of SU5416 in prostate cancer.