AGO-GYN 5: A phase II study of AEZS-108 (AN-152), a targeted cytotoxic LHRH analogue, in women with LHRH receptor positive platinum resistant ovarian cancer

Abstract

Objective: Most ovarian cancers express receptors for luteinizing hormone releasing hormone (LHRH-R). AEZS-108 (AN-152) is a targeted cytotoxic drug with doxorubicin linked to [D-Lys(6)>-LHRH. A Phase I study in women with LHRH-R positive tumours revealed a dose of 267 mg/m2 by 2-h intravenous infusion in 3-week cycles, to be well tolerated. Materials and methods: Patients with histologically confirmed taxane- pretreated platinum-resistant/refractory LHRH-R positive ovarian cancer received up to 6 cycles of AEZS-108. At least 1 measurable lesion or CA 125 C200% of the upper normal range limit were required at baseline. An independent radiological review was performed. Response rate (RECIST or GCIG criteria) was defined as primary endpoint. Secondary endpoints were time-to-progression (TTP), overall survival (OS) and safety. Results: 43 patients entered the study and received a total of 175 treatment courses. 5 patients (11.6%) developed a partial remission (PR), a stable disease for[12 weeks (SD) was reported in 14 patients (32.6%). The following haematological toxicities [grade 3 or 4 (% of pts.)> were most frequent: leucopenia 44% (G4: 9.2%), anaemia 4.6% and thrombocytopenia 2.3%. Febrile neutropenia occurred in 3 patients (7%). 6 patients (14%) received G-CSF support, 2 patients (4.6%) obtained erythrocyte concentrates. In 1 patient (2.3%) the dose was reduced to 160 mg/m2. Other non-haematological toxicities [grade 2/3 (% of pts.), no grade 4> were: alopecia 32.6%, nausea 21% (G3: 2.3%), vomiting 14%, diarrhoea 4.6%, mucositis 4.6%, allergic reaction 4.6%. No cardiac toxicity was reported. Conclusions: AEZS-108 was active in patients with heavily pretreated platinum-resistant ovarian cancer (clinical benefit rate 44%). The safety profile confirmed the dose of 267 mg/m2 to be feasible for further trials.