Phase I and pharmacokinetic study of IV vinflunine in combination with carboplatin in chemonaive patients with advanced non-small cell lung cancer.

Abstract

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.

• Authors: Caroline Tournoux-Facon, Gilles Robinet, Marie-Claire Pinel, Pierre Ferre, Jean-Marc Tourani
• Journal: American journal of clinical oncology (Am J Clin Oncol) Vol. 35 Issue 4 Pg. 378-85 (Aug 2012) ISSN: 1537-453X [Electronic] United States
• PMID: 22814308 (Publication Type: Clinical Trial, Phase I, Journal Article)

Chemical References

• vinflunine
• Vinblastine
• Carboplatin

Topics

• Adenocarcinoma (drug therapy, mortality)
• Aged
• Antineoplastic Combined Chemotherapy Protocols (pharmacokinetics, therapeutic use)
• Carboplatin (administration & dosage)
• Carcinoma, Non-Small-Cell Lung (drug therapy, mortality)
• Carcinoma, Squamous Cell (drug therapy, mortality)
• Female
• Follow-Up Studies
• Humans
• Lung Neoplasms (drug therapy, mortality)
• Male
• Maximum Tolerated Dose
• Middle Aged
• Neoplasm Staging
• Prognosis
• Survival Rate
• Tissue Distribution
• Vinblastine (administration & dosage, analogs & derivatives)