Objective: The purpose of the study was to evaluate activity and toxicity of the combination of topotecan and ifosfamide as salvage treatment in patients with advanced ovarian cancer refractory to or relapsing after platinum compound-based chemotherapy.
Methods: Thirty-nine patients entered the trial. Inclusion criteria were: previous platinum compound-based chemotherapy with or without paclitaxel, age </=75 years, ECOG PS </=2, and measurable or evaluable lesions. Treatment consisted of topotecan 1.3 mg/sqm d. 1-3 in combination with ifosfamide 1500 mg/sqm d. 1 and 2 (plus uroprotector MESNA), q. 21 days.
Results: All patients had received previous platinum compound-based chemotherapy (carboplatin + paclitaxel in 72% of patients); 15 patients had received a further second-line therapy. Overall, 179 cycles were administered; median number courses/patient was 5 (range: 1-8). Eighteen patients received at least six courses of therapy. All patients were evaluable for toxicity and 38 patients for response. Main toxicities consisted of gr3-4 neutropenia in 25%, gr3 anaemia in 18%, neutropenic fever in four patients; 7 patients required blood transfusion and 26 patients were treated with G-CSF. Dose reduction of both drugs was performed in five patients, and seven patients required 1-week delay for recovery of toxicity. Objective response was observed in 16/39 patients (41%): complete response in six patients and partial response in 10 patients; in further three patients, >/=50% reduction of baseline CA-125 was recorded. Significant higher response rate was observed in platinum-sensitive population (11/15 patients) compared to resistant disease (8/24 patients).
Conclusions: Chemotherapy with topotecan and ifosfamide (IT) in pretreated advanced ovarian cancer patients is feasible with moderate toxicity. The potential of the regimen for synergistic drug interactions deserves further evaluations.