Vinflunine in platinum‐pretreated patients with locally advanced or metastatic urothelial carcinoma

Abstract

BACKGROUND: The activity and safety of vinflunine was evaluated in patients with locally advanced or metastatic urothelial carcinoma (UC) who developed disease progression within 12 months of platinum‐containing chemotherapy. METHODS: Patients with UC were eligible if they received a prior platinum‐based regimen in the neoadjuvant/adjuvant setting or as first‐line treatment for advanced/metastatic disease and had developed disease progression within 12 months. Vinflunine was administered intravenously every 3 weeks. Patients with Karnofsky performance status of 80 or 90, impaired renal function, prior pelvic irradiation, or age ≥75 years received an initial dose of 280 mg/m2, which was escalated to 320 mg/m2 in Cycle 2 if well tolerated. All other patients received an initial dose of 320 mg/m2. The primary endpoint was response rate defined by an independent response review committee (IRRC). RESULTS: Per the IRRC, 22 patients achieved a partial response, with a response rate of 15% (95% confidence interval, 9%‐21%) with a median duration of response of 6.0 months. Sixty‐four (42%) patients had stable disease. The median progression‐free survival was 2.8 months, and the median overall survival was 8.2 months. Myelosuppression was the most frequent adverse event, with grade 3 of 4 (adverse events were evaluated according to the National Cancer Institute Common Toxicity Criteria [version 2.0] guidelines) neutropenia reported in 58% of the patients. Grade 3 of 4 febrile neutropenia occurred in 10 (7%) patients. Nonhematologic treatment‐related events (grade 3 of 4) were generally manageable and included constipation (17%), asthenia/fatigue (13%), ileus (5%), and abdominal pain (5%). No cumulative toxicity was observed. CONCLUSIONS: Vinflunine demonstrates moderate activity in patients with platinum‐pretreated UC. Toxicity is manageable and noncumulative. Cancer 2009. © 2009 American Cancer Society.

First- and Second-Line Therapy for Metastatic Urothelial Carcinoma of the Bladder

“…Toxicity consisted mainly of grade 3 or 4 neutropenia (67%) and febrile neutropenia (5%) 60 . The second trial included 175 patients with platinum-refractory bc, and in 150 patients, the or rate was 15%, with a mds of 8.2 months and a more favourable toxicity profile 65 . Based on those results, a large phase iii trial randomized 370 patients to receive either vfl with bsc or bsc alone 64 .…”

Vinflunine and bladder cancer: present and future indications

“…Compared to other vinca alkaloids, VFL has shown a better safety profile, inducing a smaller degree of neuropathy and its early resolution after drug withdrawal. [13][14][15][16][17][18] Other adverse events reported were mucositis and neutropenia, which were of low grade and of prompt resolution after the appropriate therapy. In the phase III trial conducted by Bellmunt et al, 16 VFL has demonstrated the ability to improve the outcome of patients with advanced UC which progressed after a first-line cisplatin-containing chemotherapy.…”

“…Importantly, VFL did not induced the dose-limiting neurotoxicity observed for other vinca alkaloids. [13][14][15][16][17] More recently, Harshman et al 17 studied the possible impact of a prior first-line cisplatin chemotherapy on the outcome of patients enrolled in the aforementioned trial. 16 As expected, the impact of VFL on the outcome was independent of prior chemotherapy; the drug was able to prolong OS among in both cisplatin-pretreated patients and those who did not receive cisplatin.…”

“…[7][8][9][10][11][12] Interestingly, contrasting results were reported for patients included in second-line studies after failure of neoadjuvant or adjuvant therapy compared to patients at relapse after first-line. [14][15][16][17][18][19] Because of their good activity in UC, taxanes may be compared with VFL as second-line chemotherapy. A randomized, head-to-head, phase II trial, which started its enrollments in October 2012, is ongoing and is comparing VFL at standard doses versus cabazitaxel, a thirdgeneration taxane.…”

“…13 The clinical activity of VFL in patients with metastatic UC was initially assessed in phase II and III trials showing good activity and a favorable toxicity spectrum (Table 2). [14][15][16][17] As result of these studies, VFL was the first drug to receive approval from the European Medicines Agency (EMA) for use in platinum-resistant metastatic UC patients.…”