vinflunine and Carcinoma--Large-Cell

Vinflunine (Javlor) has shown significant antitumour activity in advanced non-small cell lung cancer (NSCLC). We propose to define the recommended dose of vinflunine in combination with gemcitabine for treatment of advanced NSCLC in chemonaive patients.. A phase I and pharmacokinetic study was conducted to determine the maximum tolerated dose and to establish the recommended dose of vinflunine (VFL) administered on day 1 every 21 days combined with gemcitabine given on days 1 and 8 every 3 weeks.. Nineteen patients were included in this study. Three patients experienced a dose limiting toxicity, with constipation in one patient, hypertension in one patient, and constipation and febrile neutropenia in one patient. The combination of VFL 320 mg/m² and gemcitabine 1250 mg/m² was defined as the maximum tolerated dose. The recommended dose was established at the dose of VFL 320 mg/m² combined with gemcitabine 1000 mg/m². Neither VFL nor gemcitabine seemed to be influencing the pharmacokinetics of each other. All patients were evaluable for tumor response. Seven presented a partial response and eight experienced a stable disease.. The combination of VFL 320 mg/m² administered on day 1 combined with gemcitabine 1000 mg/m² given on days 1 and 8 every 3 weeks is established as the RD and was shown to be active in these chemonaive NSCLC patients.

Topics: Adenocarcinoma; Aged; Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Large Cell; Carcinoma, Non-Small-Cell Lung; Carcinoma, Squamous Cell; Deoxycytidine; Female; Follow-Up Studies; Gemcitabine; Humans; Lung Neoplasms; Lymphatic Metastasis; Male; Maximum Tolerated Dose; Middle Aged; Neoplasm Recurrence, Local; Neoplasm Staging; Survival Rate; Tissue Distribution; Treatment Outcome; Vinblastine

A multicenter phase I/II trial of vinflunine administered in combination with cisplatin at 80 mg/m(2) was conducted in order to determine the dose-limiting toxicities, the maximum tolerated dose, and the recommended dose of the combination. An eventual mutual pharmacokinetic drug-drug interaction when vinflunine and cisplatin were coadministered was also evaluated. The study was also intended to define the response rate of vinflunine in combination with cisplatin as first-line chemotherapy in patients with advanced non-small-cell lung cancer (NSCLC) at the recommended dose.. Patients were required to have a histologically confirmed diagnosis of NSCLC not amenable to curable treatment or stage IV disease. Patients may have had previous surgery for NSCLC but were to be chemonaive and have at least 1 bidimensional measurable lesion outside an irradiated area.. The recommended dose was established at cisplatin 80 mg/m2 combined with vinflunine 320 mg/m(2). No unexpected adverse events were seen. Pharmacokinetic analysis supported the absence of mutual pharmacokinetic interaction when vinflunine and cisplatin are given in combination. Treatment of 53 patients at this recommended dose demonstrated a tumor response rate of 32.1% in the intent-to-treat population; disease control was achieved in 79.2% of the patients. The median progression-free survival and overall survival were estimated at 5 months and 10.4 months, respectively, and the 1-year survival rate was 43.4%.. These results place the vinflunine/cisplatin combination among the most active doublets in this treatment setting and warrant further development in phase III trials of first-line treatment of patients with advanced metastatic NSCLC.

Topics: Adenocarcinoma; Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Large Cell; Carcinoma, Non-Small-Cell Lung; Carcinoma, Squamous Cell; Cisplatin; Female; Humans; Injections, Intravenous; Lung Neoplasms; Male; Maximum Tolerated Dose; Middle Aged; Neoplasm Staging; Survival Rate; Tissue Distribution; Treatment Outcome; Vinblastine