Maintenance chemotherapy with oral treosulfan following first-line treatment in patients with advanced ovarian cancer: feasibility and toxicity.

Purpose: To evaluate the feasibility and toxicity of maintenance oral treosulfan chemotherapy for ovarian cancer patients after surgical treatment and response to first-line chemotherapy. Patients and Methods: Thirty-nine patients were entered onto this trial. This was a pretreated patient population. The pretreatment consisted of radical surgery and chemotherapy. The treatment that immediately preceded oral treosulfan was standard-dose platin-based chemotherapy. Daily oral treosulfan was administered at a dose of 1250 mg for 5 consecutive days every five weeks for at least three cycles. All patients started daily oral treosulfan while in complete remission. Results: A total of 322 cycles of oral treosulfan was administered, with a median of 6 cycles (range 3-24). Treosulfan in this schedule was generally well tolerated. The major toxic effects were leukopenia and thrombocytopenia, which, however, were manageable and rapidly reversible. There were no episodes of bleeding or leukopenic fever. No anti-emetic drugs were required. Alopecia was not observed. 20 patients had progressive disease (after 3-6 months: n=8, after >6 months: n=12). The median survival for all patients was 24 (range 9-44 + ) ) months, and median time to progression 8 (range 3-24) months. Conclusions: Maintenance oral treosulfan was well tolerated in this pretreated patient population. In an attempt to further improve overall survival in ovarian cancer patients, prospective random assignment trials will be necessary to determine the benefit of this approach. is primarily resistant, or when relapse occurs, the prospects for second-line treatment are unsatisfactory. Previous studies in the situation, either with single agents or combination chemotherapy, have generally shown few responses of short duration [1, 8, 10, 18]. Even the promising new agent paclitacel (Taxol®) induces responses in only 20-30% of this group of patients [5, 11, 15, 19]. Treosulfan (hydroxybusulfan; L-threitol 1, 4-dimethanesulfonate) has demonstrated single-agent activity in ovarian cancer [4, 7, 20]. Prolonged administration of oral treosulfan has been studied in refractory ovarian cancer [9]. We performed a trial with oral maintenance treosulfan in patients who had achieved complete remission following initial surgical treatment and first-line platin combination chemotherapy in order to analyse the feasibility and toxicity of this treatment.