Phase II study of NGR-hTNF in combination with doxorubicin in relapsed ovarian cancer patients

BACKGROUND: The NGR-hTNF (asparagine-glycine-arginine-human tumour necrosis factor) is able to promote antitumour immune responses and to improve the intratumoural doxorubicin uptake by selectively damaging tumour blood vessels. METHODS: Patients progressing after >= 1 platinum/taxane-based regimen received NGR-hTNF 0.8 mu g m(-2) and doxorubicin 60 mg m(-2) every 3 weeks. Primary endpoint was a Response Evaluation Criteria in Solid Tumors-defined response rate with a target of more than 6 out of 37 responding patients. RESULTS: A total of 37 patients with platinum-free interval lower than 6 months (PFI < 6; n = 25), or between 6 and 12 months (PFI = 6-12; n = 12) were enrolled. Median baseline peripheral blood lymphocyte count (PBLC) was 1.6 per ml (interquartile range, 1.2-2.1). In all, 18 patients (49%) received more than 6 cycles. Febrile neutropaenia was registered in one patient (3%). Among 35 assessable patients, 8 (23%; 95% CI 12-39%) had partial response (2 with PFI < 6; 6 with PFI = 6-12) and 15 (43%) had stable disease (10 with PFI < 6; 5 with PFI = 6-12). Median progression-free survival (PFS) was 5.0 months for all patients, 3.8 months for patients with PFI < 6, and 7.8 months for patients with PFI = 6-12. Median overall survival (OS) was 17.0 months. Patients with baseline PBLC higher than the first quartile had improved PFS (P = 0.01) and OS (P = 0.001). CONCLUSION: Tolerability and activity of this combination warrant further randomised testing in patients with PFI < 6. The role of PBLC as a blood-based biomarker deserves further investigation. British Journal of Cancer (2012) 107, 37-42. doi:10.1038/bjc.2012.233 www.bjcancer.com Published online 29 May 2012 (C) 2012 Cancer Research UK