METRO1: A Phase I Study of Metronomic Chemotherapy in Adults with Advanced Refractory Solid Tumors

Background: The present monocentric and prospective phase 1 study evaluated the safety of a metronomic chemotherapy in refractory tumors. Patients and Methods: Patients with advanced solid cancer refractory to standard therapy received a combination of low-dose vinorelbine, cyclophosphamide and interferon-alpha. A dose escalation model with 3 levels was planned. The primary end-point was safety and tolerability, secondary end-points were treatment continuation rate at 4 months, progression-free survival (PFS), overall survival (OS), radiological assessment (MRI) of anti-angiogenic effect. Results: Thirty patients were enrolled. No dose-limiting toxicity was observed. All but two adverse events were toxicities of grade 1-2. Treatment continuation rate at 4 months was 6.67% (2 out of 30 patients). Median PFS and OS were 1.6 and 6.1 months. Exploratory MRI analyses related to anti-angiogenic effect did not show any relevant modification. Conclusion: This combination of metronomic chemotherapy is well-tolerated and deserves to be deeply explored in refractory solid tumors.