A phase II trial of gallium nitrate in patients with androgen-metastatic prostate cancer

Introduction: Due to in vitro data suggesting antitumor activity with gallium nitrate, we sought to evaluate the safety and activity in patients with androgen-independent prostate cancer. Method: Patients were eligible for this study if they had an ECOG performance status of ≤ 2, stage D2 metastatic prostate cancer that was progressing following combined androgen ablation (medical or surgical castration plus antiandrogen) and had failed antiandrogen withdrawal. Therapy consisted of gallium nitrate (200 mg/m²/day) as a continuous infusion for 7 days, administered every 21 days, with hydration (100 ml/m²/h). Individuals that had previously received suramin were treated at a dose of 150 mg/m²/day of gallium nitrate. Results: Eight patients were enrolled. 4 patients at the 200 mg/m²/day dose level and 4 patients at the lower dosage (150 mg/m²/day). One of 8 patients had a > 75% decline in prostate-specific antigen (PSA), 3 patients had stable PSA values for 17, 18 and 22 weeks, and 4 patients had progression by PSA (> 50% increase over baseline). Anemia requiring transfusion occurred in 5 of 8 patients (63%). Two patients (25%) developed grade 4 toxicity: 1 patient developed complete blindness with partial reversal over 12 months, and another patient had pulmonary infiltrates, hypoxemia, and fever. Serious adverse events were not correlated to prior suramin exposure, or gallium plasma concentrations (total or free), but appeared to be related to cumulative cycles of gallium nitrate. Remaining adverse events were grade 1 or 2. No patients developed renal or neurological toxicity. Conclusion: This trial was prematurely terminated because repeated administration of gallium nitrate was poorly tolerated in an elderly population with androgen-independent prostate cancer. Gallium had modest clinical activity in this disease.