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.
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.
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/m2) and carboplatin AUC6 was defined as the maximum tolerated dose. The RD was established at the dose of VFL (320 mg/m2) 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.
The combination of VFL (320 mg/m2) 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.
*Centre d'Investigation Clinique
§Oncologie Médicale, CHU de Poitiers, Université de Poitiers
†Institut de Cancérologie et Hématologie, CHU Morvan, Brest
‡Institut de Recherche Pierre Fabre, Boulogne-Billancourt, France
Marie-Claire Pinel: Vinflunine Project Leader, Institut de Recherche Pierre Fabre; Pierre Ferre: Director of Pharmacokinetic Dept, Oncology Development, Institut de Recherche Pierre Fabre. The other authors declare no conflicts of interest.
Reprints: Marie-Claire Pinel, MD, Institut de Recherche Pierre Fabre, Boulogne-Billancourt, France. e-mail: firstname.lastname@example.org.