A multicenter phase I trial of metronomic oral vinorelbine plus cisplatin in patients with NSCLC

Abstract

The purpose of the present study was to determine the maximum tolerated doses

Phase I Study of Oral Vinorelbine in Combination with Erlotinib in Advanced Non-Small Cell Lung Cancer (NSCLC) Using Two Different Schedules

“…Although it would be premature to conclude based on the results of this study alone, given the limited data and nature of phase I studies, it is possible that peak plasma concentrations of vinorelbine need to reach certain therapeutic thresholds for its anti-tumour activities to be effective, which could not be achieved with low-dose metronomic dosing. Nonetheless, in line with the encouraging data reported by other investigators on the anti-cancer efficacy of metronomic vinorelbine in several types of cancer [ 16 ], [ 17 ], [ 22 ], [ 23 ], the overall response rate in the MSV group in this study was 29%, with median PFS of 7.5 months and median OS of 11.0 months. These findings were comparable to those of Del Conte et al which evaluated the tolerability and efficacy of metronomic vinorelbine monotherapy in lung cancer patients [ 24 ].…”

“…However, all the four patients who received higher vinorelbine dose of 140 mg/week with erlotinib 100 mg/day experienced grade 3/4 neutropenic fever, two of which were considered DLTs. These findings were in contrast with those noted by Pallis et al and Briasoulis et al, which reported that the administration of oral vinorelbine doses up to 60 mg every other day and 50 mg thrice weekly in each cycle respectively was characterized by acceptable toxicities [ 17 ], [ 22 ]. Moreover, Pallis et al conducted the study in patients receiving oral vinorelbine in combination with cisplatin, while Briasoulis et al conducted a study in which vinorelbine was administered as a monotherapy [ 17 ], [ 22 ].…”

“…These findings were in contrast with those noted by Pallis et al and Briasoulis et al, which reported that the administration of oral vinorelbine doses up to 60 mg every other day and 50 mg thrice weekly in each cycle respectively was characterized by acceptable toxicities [ 17 ], [ 22 ]. Moreover, Pallis et al conducted the study in patients receiving oral vinorelbine in combination with cisplatin, while Briasoulis et al conducted a study in which vinorelbine was administered as a monotherapy [ 17 ], [ 22 ]. One possible explanation for the observed haematological toxicity at this dose level (vinorelbine 140 mg/week plus erlotinib 100 mg/day) in our study but not others could be due to the altered pharmacokinetics of vinorelbine at steady state when administered together with erlotinib, both of which are substrates of CYP3A4.…”

Metronomic oral vinorelbine in patients with advanced non-small cell lung cancer progressing after nivolumab immunotherapy: a retrospective analysis

“…Among chemotherapeutic agents employed in advanced NSCLC vinorelbine (VNR) has shown good anti-tumour activity and acceptable safety both after intravenous and oral administration [ 6 , 7 ]. In the last decade, oral VNR has also been tested as single agent or in combination with platinum compounds in some phase I-II trials on a metronomic schedule, i.e., the administration of prolonged, non-stop low doses of otherwise active drugs [ 8 – 11 ]. In these studies, a flat dose in the range of 30–50 mg three times per week has been identified as the optimal schedule in terms of tolerability.…”

Metronomic treatment of advanced non-small-cell lung cancer with daily oral vinorelbine – a Phase I trial

“… 25 , 26 Preliminary data indicate that fractionated doses of 70 mg/m 2 /wk split over days 1, 3 and 5 as well as fixed doses of up to 60 mg every other day are well tolerated and show activity in some patients. 27 , 28 …”