Phase II Trial of Vinflunine in Relapsed Small Cell Lung Cancer

Background Vinflunine is a new microtubule inhibitor with preclinical activity in small cell lung cancer (SCLC). In this phase II trial, we evaluated vinflunine in patients with relapse-sensitive and refractory SCLC. Methods This trial aimed to achieve a 20% objective response rate (ORR) in platinum-sensitive patients. Patients with Eastern Cooperative Oncology Group performance status 0 to 2 and measurable disease received vinflunine (320 mg/m 2 IV) every 21 days (≤6 cycles; response evaluation every 6 weeks). Results Patient characteristics ( N = 51): median age 63 years (range, 37–85 years); male, 55%; Eastern Cooperative Oncology Group performance status 2, 16%; relapse-sensitive SCLC, 53%. The overall ORR was 19.6% (95% confidence interval [CI] 10–33%). Twelve (23.5%) patients had stable disease; 18 (35.3%) patients had progressive disease. Among relapse-sensitive patients, ORR was 22.2% (95% CI 9–42%). Among relapse-refractory patients, ORR was 16.7% (95% CI 5–37%). Median follow-up was 15 months (range, 12–18 months); median progression-free survival (PFS) was 1.6 months (95% CI 1.3–3.9 months); median overall survival (OS) was 4.9 months (95% CI 3.2–6.5 months). Among relapse-sensitive patients, PFS and OS were 1.6 and 4.9 months, respectively. Among relapsed-refractory patients, PFS and OS were 1.4 and 4.0 months, respectively. In general, vinflunine was well tolerated, although neutropenia was a notable toxicity. Grade 3/4 toxicities (>5%): neutropenia (32%), arthralgia/myalgia (16%), fatigue (16%), hyponatremia (12%), leukopenia (12%), nausea/vomiting (12%), constipation (6%), and thrombocytopenia (6%). The rates of toxicities were relatively well balanced among relapse-sensitive and refractory patients; one patient died of sepsis that was possibly treatment related. Conclusions Vinflunine has activity in relapsed SCLC, including refractory relapsed patients. Neutropenia was common but associated with rare febrile episodes. Additional study in relapse-refractory SCLC is indicated.