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Phase I and Pharmacokinetic Study of IV Vinflunine in Combination With Carboplatin in Chemonaive Patients With Advanced Non-small Cell Lung Cancer

Tournoux-Facon, Caroline, MD*; Robinet, Gilles, MD; Pinel, Marie-Claire, MD; Ferre, Pierre, DVM; Tourani, Jean-Marc, MD§

American Journal of Clinical Oncology: August 2012 - Volume 35 - Issue 4 - p 378–385
doi: 10.1097/COC.0b013e3182143d93
Original Articles: Thoracic
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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/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.

Conclusions 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: marie.claire.pinel@pierre-fabre.com.

© 2012 by Lippincott Williams & Wilkins, Inc