Phase III trial comparing vinflunine with docetaxel in second-line advanced non-small-cell lung cancer previously treated with platinum-containing chemotherapy.

PURPOSE: To compare vinflunine (VFL) to docetaxel in patients with stage IIIB/IV non-small-cell lung cancer (NSCLC) who have experienced treatment failure with first-line platinum-based chemotherapy. PATIENTS AND METHODS: Randomized, multicenter, phase III study, 551 patients received either vinflunine 320 mg/m(2) or docetaxel 75 mg/m(2) every 21 days until disease progression or serious toxicity. The primary end point was progression-free survival (PFS). The noninferiority analysis was based on a 10% difference (types I/II error rates: 5%/20%). Secondary end points included response rate (ORR), response duration, overall survival (OS), clinical benefit, quality of life (QOL), and safety. RESULTS: Median PFS was 2.3 months for each arm (HR, 1.004; 95% CI, 0.841 to 1.199). ORR, stable disease, median OS, were 4.4% versus 5.5%, 36.0% versus 39.6%, 6.7 versus 7.2 months (HR, 0.973; 95% CI, 0.805 to 1.176), respectively. No significant difference in patient benefit and QOL (Functional Assessment of Cancer Therapy-Lung). No unexpected adverse events were observed. Grade higher than 0 (vinflunine v docetaxel) anemia (82.1% v 79.8%), neutropenia (49.3 v 39.02%), thrombocytopenia (30.6% v 14.3%), febrile neutropenia (3.3% v 4.7%), constipation (39.2% v 11.7%), fatigue (36.6% v 33.9%), injection site reaction (31.9% v 0.7%), nausea (26.7% v 23.7%), vomiting (23.8% v 14.2%), alopecia (19.8% v 35.4%), stomatis (19.4% v 12.4%), abdominal pain (20.1% v 3.6%), myalgia (14.7% v 6.6%), peripheral neuropathy (10.7% v 15.0%), arthralgia (7.0% v 7.7%), diarrhea (6.2% v 12.4%), edema (1.5% v 5.4%), and nail disorders (1.1% v 5;1%) were observed. CONCLUSION: This noninferiority phase III study showed similar efficacy end points for vinflunine and docetaxel. Despite higher rates of some adverse effects (anemia, abdominal pain, constipation, fatigue) the overall toxicity profile of vinflunine was manageable. Therefore, VFL may be another option in the second-line treatment of patients with advanced NSCLC.

Higher antitumor activity of vinflunine than vinorelbine against an orthotopic murine model of transitional cell carcinoma of the bladder.

The aim of this report was to investigate the feasibility of systemic treatment of transitional cell carcinoma of the bladder with vinflunine (VFL), and to compare its activity in respect to vinorelbine (VRL). Exposure of MB49 murine bladder cancer cells to both drugs showed a higher chemosensitivity of the cells to VRL than to VFL (IC50 values of 60 nM and 400 nM, respectively). Pretreatment of MB49 cells with non-cytotoxic drug concentrations revealed an inhibition of control in vitro invasiveness of 40 to 70% (1-25 nM VRL) and 22 to 80% (1-100 nM VFL) (P < 0.0001, ANOVA). The intraperitoneal administration of the drugs twice a week for 4 weeks in C57B1/6 female mice revealed that VFL was very well tolerated, with a 8-fold increase in the maximum tolerated dose in respect to VRL (40 mg/kg and 4.8 mg/kg, respectively). The administration schedule was evaluated in C57B1/6 female mice inoculated transurethraly with 5 x 10(4) MB49 cells. Intravesical tumor incidence on day 21 was 0% and 17% in mice treated intraperitoneally with 20 and 10 mg/kg VFL respectively (P = 0.0017 and P = 0.0001, Fischer's Exact Test), contrasting with 75-83% obtained in all VRL-treated groups and Controls. All mice treated with 20 mg/kg VFL were still alive 60 days after intravesical MB49 tumor implantation, as well as 50% of those treated with 10 mg/kg VFL, while most of the remaining mice (Control and VRL-treated) died before day 32. These studies clearly demonstrate the activity of VFL against a murine bladder cancer model, with a favorable toxicity profile.