vinflunine and Carcinoma--Small-Cell

Vinflunine is a novel microtubule inhibitor of the vinca alkaloid class currently in development for the treatment of advanced transitional cell carcinoma of the urothelium (TCCU) and other solid tumors. This review summarizes the clinical activity of vinflunine as a single agent or in combination with other antineoplastic drugs. Vinflunine is active against a variety of tumor types, including advanced TCCU, metastatic breast cancer, advanced non-small cell lung cancer, and malignant pleural mesothelioma. It has a manageable and noncumulative toxicity profile, and its specific mechanism of action has been linked to a reduced potential for peripheral sensory neuropathy. The activity and tolerability of this agent warrant further investigation. Phase 3 trials are underway to further define the extent of clinical benefit provided by vinflunine in patients with advanced solid malignancies.

Topics: Animals; Antineoplastic Agents, Phytogenic; Breast Neoplasms; Carcinoma, Non-Small-Cell Lung; Carcinoma, Small Cell; Carcinoma, Transitional Cell; Clinical Trials as Topic; Humans; Mesothelioma; Mice; Pleural Neoplasms; Tubulin Modulators; Urinary Bladder Neoplasms; Urothelium; Vinblastine

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.. 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 (< or =6 cycles; response evaluation every 6 weeks).. 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.. 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.

Topics: Adult; Aged; Aged, 80 and over; Antineoplastic Agents, Phytogenic; Carcinoma, Small Cell; Disease-Free Survival; Female; Humans; Lung Neoplasms; Male; Microtubules; Middle Aged; Neoplasm Recurrence, Local; Vinblastine