PHASE-II STUDY OF TOPOTECAN IN METASTATIC HORMONE-REFRACTORY PROSTATE-CANCER

Systemic chemotherapy with currently available agents has not improved survival for patients with hormone refractory prostate cancer (HRPC), consequently, the evaluation of new agents is warranted. Topotecan is a specific inhibitor of topoisomerase I with broad antitumor activity in preclinical studies. The purpose of this phase II trial was to det ermine the objective response rate of topotecan administered as a 30 m inute infusion for five consecutive days in men with metastatic HRPC. Thirty-four evaluable patients were treated with topotecan 1.1-1.5 mg/ m(2) as a 30 minute infusion daily for five days, repeated every three weeks until disease progression or unacceptable toxicity. Response wa s assessed with a combination of standard solid tumor response criteri a and the serum prostate specific antigen (PSA) for patients with bidi mensionally measurable disease, and by serial measurements of the PSA in patients with bone only (evaluable) disease. One of 13 patients (7. 6%) with measurable soft tissue disease had a PR in nodal sites. Of 21 patients with only osseous metastases, 1 (4.7%) had improvement in bo ne scan. Six of the 34 evaluable patients (17.6%) had the serum PSA de crease by greater than or equal to 50% and 2 (5.8%) had PSA decreases of greater than or equal to 75%. Toxicity was chiefly hematologic with 66% of patients experiencing Grade 3 or 4 granulocytopenia. Thirty-ni ne percent of cycles required a delay to allow for hematologic recover y and ten patients required red cell transfusions. Nonhematologic toxi city, mainly nausea and alopecia, was mild. Topotecan administered at this dose and schedule has limited activity in patients with HRPC. Fur ther trials of topo I inibition in HRPC should utilize alternative sch edules of topotecan (e.g., prolonged infusion) or other camptothecin a nalogs with more potent topo I inhibitory activity.