A prospective multicenter study of treosulfan in elderly patients with recurrent ovarian cancer: results of a planned safety analysis

Abstract

BackgroundTreosulfan, an alkylating agent, has demonstrated activity in recurrent ovarian carcinoma. It is equieffective as oral (p.o.) and intravenous (i.v.) formulation. To explore the preference and compliance of elderly patients regarding p.o. or i.v. treosulfan for the treatment of relapsed ovarian carcinoma, women aged 65 years or older were included in this prospective multicenter study. Since elderly patients usually have several concomitant diseases and experience more treatment toxicity, an interim safety analysis was planned and performed after 25 patients finished therapy to assess the tolerability of the treatment regimens.MethodsPatients had a free choice of treosulfan i.v. (7,000 mg/m2 day 1 of a 28-day cycle) or p.o. (600 mg/m2 day 1–28 of a 56-day cycle) for a maximum of 12 cycles (i.v.) or 12 months (p.o.). Indecisive patients were randomized. Toxicity was evaluated according to the NCI-CTC version 2.0.ResultsTwenty-five of 51 recruited patients completed therapy at the time of the planned interim analysis (median age, 75 years; range, 70–82). Median ECOG was 1, and median number of prior chemotherapy regimens was 2. A median number of 4 cycles (range, 1–12) were administered per patient. Anemia was the most common hematological toxicity (88 % of patients). Most frequent non-hematological toxicities were nausea (76 %), constipation (68 %), and fatigue (64 %).ConclusionTreatment was generally well tolerated despite the fact that most patients suffered from multiple comorbidities and were heavily pretreated. There were no unexpected hematological or non-hematological toxicities. Based on this safety analysis, the next step of study recruitment was continued.

A phase III, open label, randomized multicenter controlled trial of oral versus intravenous treosulfan in heavily pretreated recurrent ovarian cancer: a study of the North-Eastern German Society of Gynecological Oncology (NOGGO)

“…As in our study, in total leucopenia and thrombocytopenia were among the most frequently reported grade III/IV toxicities. The frequency of observed thrombocytopenia (7.2%) is comparable with those published by Meier et al (2009) (7.5%) and Mahner et al (2012) (4.0%). In contrast, the frequency of leucopenia observed in the treosulfan i.v.…”

“…arm). Toxicities during therapy with intravenous treosulfan had been reported in several previous studies (Meier et al 2009; Mahner et al 2012). However, safety data on therapy with oral treosulfan are rare.…”

Programmed Erythrocyte Death Following in Vitro Treosulfan Treatment

“…The stimulation of eryptosis contributes to or even accounts for the anemia observed in the vast majority of patients following Treosulfan treatment [10]. Eryptotic erythrocytes are phagocytosed and rapidly cleared from circulating blood [12].…”

“…The substance is at least in part effective by triggering apoptosis [2,3,4,5,6,7,8,9]. The most common side effect of Treosulfan treatment is anemia, affecting as many as 88% of the patients [10]. …”

Understanding and managing medication in elderly people

“…In elderly women with advanced ovarian cancer (median age 75 years; range 70-82 years), the median number of concomitant diseases was 5 (range 1-9) [29]. The most common comorbidities were hypertension, diabetes mellitus, cardiovascular, and musculoskeletal disease [27,29].…”