Pazopanib with Topotecan weekly for patients with platinum-resistant or intermediate-sensitive recurrent ovarian cancer: results of a multicentre, open label phase I/II study (TOPAZ).

Pazopanib has promising antiangiogenetic activity in solid cancers. The investigator-initiated phase I/II trial evaluated the combination of Topotecan with Pazopanib in platinum-resistant or intermediate-sensitive recurrent ovarian cancer (ROC). Patients (≥ 18 years) with first or second recurrence were enrolled in this multicentre open-label trial. Phase I analysed Topotecan 4 mg/m Between June 2012 and February 2017, 11 patients were enrolled in the phase I, and 50 patients in the phase II study. The MTD of Pazopanib was determined by 400 mg/daily. Haematological and liver toxicities determined the dose limiting toxicities (DLT) and the most common grade 3-4 adverse events: leucopenia (25%), neutropenia (22%), thrombocytopenia (19%), accumulation of cholestatic (20%) and hepatocellular damage (15%), which often caused dose modifications, but no new life-threatening events. Overall response was 16% and clinical benefit rate 68%. Median progression-free survival (PFS) was 3.5 months (95% CI 2.0-5.0). Due to early progression only 20% of the patients were able to start with maintenance treatment. The combination of pazopanib and weekly topotecan is feasible, resulting in a manageable haematological and liver toxicity, but despite its encouraging response rate, was not associated with a significant survival benefit.

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