Addition of vandetanib to pegylated liposomal doxorubicin (PLD) in patients with recurrent ovarian cancer. A randomized phase I/II study of the AGO Study Group (AGO-OVAR 2.13)

Background PLD is a standard treatment in patients with recurrent platinum-resistant or refractory ovarian cancer. Vandetanib is an oral once daily administered inhibitor of VEGFR-, EGFR- and RET-signaling with activity in combination with chemotherapy in some solid tumours. We aimed to establish a feasible combination therapy of PLD and vandetanib in ovarian cancer. Methods Eligible patients were treated with PLD 50 mg/m² q28 and vandetanib 100 mg/d po. It was planned to recruit at least 10 patients evaluable for toxicity over 2 treatment cycles. Primary endpoints were tolerability and safety; secondary endpoint was efficacy. Results Fourteen of 15 registered patients started treatment and were evaluable for toxicity. Three patients (21 %) stopped after first cycle (PD, withdrawal of consent, nausea/vomiting). The remaining 11 patients were treated for at least 2 cycles. Dose reductions of PLD and vandetanib were indicated in 4 (29 %) and 5 patients (36 %), respectively. The following G3/4 toxicities occurred per patient: 2 (14 %) elevated liver enzymes G3, 2 (14 %) neutropenia G3/4, 5 (36 %) PPE G3/4, 2 (14 %) mucositis G3. Tyrosine kinase inhibitor attributed side effects like hypertension or bowel perforations were not reported. Toxicity led to cessation of treatment in 4 patients (29 %). Ten patients were evaluable for response: PR 1, SD 4. The median PFS was 6.7 months and median OS was 11.1 months. Conclusions The combination of PLD 50 mg/m²q28 and vandetanib 100 mg/d is feasible, but may be intolerable due to reported toxicity.