OBJECTIVE: Vinflunine (VFL) (Javlor(®)), a novel fluorinated semisynthetic vinca alkaloid has shown significant antitumor activity in advanced non-small cell lung cancer (NSCLC). We propose to define the recommended dose (RD) of VFL in combination with carboplatin in advanced NSCLC patients. METHODS: This phase I and pharmacokinetic study was designed to determine the maximum tolerated dose and to establish the RD of VFL in combination with carboplatin. Twenty-one chemonaive patients with advanced NSCLC were treated with a first-line chemotherapy of VFL and carboplatin both given on day 1 every 3 weeks with 3 dose levels. RESULTS: Five patients experienced a dose limiting toxicity consisting of constipation in 2 patients and febrile neutropenia in 2 patients. One patient experienced grade 3 abdominal pain concurrent with grade 4 neutropenia. The combination of VFL (320 mg/m(2)) and carboplatin AUC6 was defined as the maximum tolerated dose. The RD was established at the dose of VFL (320 mg/m(2)) combined with carboplatin AUC5. At the RD, 12 patients received a median number of 3 cycles of the combination. Neither VFL nor carboplatin seemed to be influencing the pharmacokinetics of the other. Among 19 patients evaluable for tumor response, 7 had a partial response and 7 experienced stable disease. CONCLUSIONS: The combination of VFL (320 mg/m(2)) and carboplatin AUC 5 given once every 3 weeks is established as the RD of the combination, which was shown to be active in these chemonaive NSCLC patients.
OBJECTIVE:Vinflunine (VFL) (Javlor(®)), a novel fluorinated semisynthetic vinca alkaloid has shown significant antitumor activity in advanced non-small cell lung cancer (NSCLC). We propose to define the recommended dose (RD) of VFL in combination with carboplatin in advanced NSCLCpatients. METHODS: This phase I and pharmacokinetic study was designed to determine the maximum tolerated dose and to establish the RD of VFL in combination with carboplatin. Twenty-one chemonaive patients with advanced NSCLC were treated with a first-line chemotherapy of VFL and carboplatin both given on day 1 every 3 weeks with 3 dose levels. RESULTS: Five patients experienced a dose limiting toxicity consisting of constipation in 2 patients and febrile neutropenia in 2 patients. One patient experienced grade 3 abdominal pain concurrent with grade 4 neutropenia. The combination of VFL (320 mg/m(2)) and carboplatin AUC6 was defined as the maximum tolerated dose. The RD was established at the dose of VFL (320 mg/m(2)) combined with carboplatin AUC5. At the RD, 12 patients received a median number of 3 cycles of the combination. Neither VFL nor carboplatin seemed to be influencing the pharmacokinetics of the other. Among 19 patients evaluable for tumor response, 7 had a partial response and 7 experienced stable disease. CONCLUSIONS: The combination of VFL (320 mg/m(2)) and carboplatin AUC 5 given once every 3 weeks is established as the RD of the combination, which was shown to be active in these chemonaive NSCLCpatients.
Authors: M De Santis; P J Wiechno; J Bellmunt; C Lucas; W-C Su; L Albiges; C-C Lin; E Senkus-Konefka; A Flechon; L Mourey; A Necchi; W C Loidl; M M Retz; N Vaissière; S Culine Journal: Ann Oncol Date: 2015-12-16 Impact factor: 32.976