An open label phase II trial of glufosfamide: A β-D-glucose-linked isophosphoramide mustard given as 1-hour infusion in patients with advanced breast cancer

Abstract

646 Background: Glufosfamide (Glufo) is a new alkylating agent in which the active metabolite is linked to β-D-glucose to target the glucose transporter system and increase intracellular uptake in tumor cells. The aim of this study was to evaluate the activity and the safety profile of Glufo administered as 2nd line chemotherapy in patients (pts) with metastatic and inoperable breast cancer. Methods: Pts received 5000 mg/m2 of Glufo as a 1-hour infusion every 3 weeks. Anti-tumor activity was assessed according to RECIST criteria and toxicity according to CTC 2.0. The study was approved by the appropriate ethical committees and pts gave written informed consent. Results: Twenty-two pts were included over a 20-month period and all pts received treatment (median age 51 years, WHO performance status 0/1/2: 1/9/12 pts). A total of 42 treatment cycles were administered in 22 pts. Anti-tumor activity: Partial response was observed in 3 of 22 pts (14%) for the ITT population (PP population 3 of 11 pts). Eight of 22 pts (36%) had stable disease. All responders previously failed cyclophoshpamide therapy. Safety profile: Myelotoxicity was generally mild not exceeding CTC grade 2. A decrease of creatinine clearance to CTC grade 3 was observed in 2 pts. Other CTC grade 3 adverse events “likely” or “not assessable “ related to Glufo were vomiting (4 pts), fatigue (1 pt), and neuritis (1 pt). The most frequently observed adverse reaction was nausea, effecting 13 pts, but not exceeding grade 2. No hematuria was observed. Conclusions: Glufo administered as 2nd line chemotherapy revealed anti-tumor activity in breast cancer pts who had previously received an alkylator. Myelotoxicity toxicity was particularly mild. Monitoring of renal function was required. Taken together, our data indicate activity of Glufo in advanced breast cancer and warrant further investigation. Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Threshold Pharmaceuticals Threshold Pharmaceuticals Threshold Pharmaceuticals