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 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 PFI6; 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 PFI6, 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.