Anticancer agent - vinflunine

Four vinca alkaloids are currently in use as anticancer treatments: vincristine, vinblastin, vindesine and vinorelbin. A new difluorinated semisynthetic derivative, vinflunine, has been developed by Pierre Fabre, and licensed to Bristol-Myers Squibb.¹ Preclinical models showed it to be more effective than vinorelbine, and it has marked antitumour activity in vivo against a wide range of tumours.²

Phase I trials were carried out to establish safe dosing levels.³ A total of 31 patients were given a 10 minute intravenous infusion of vinflunine every three weeks with an escalating schedule of doses between 30 and 400mg/m². The recommended dose was established at 350mg/m². Three partial responses were observed, two in pre-treated patients with metastatic breast cancer and one in a treatment naïve patient with renal cell carcinoma.

A trial has been carried out in 53 patients who had been pre-treated for advanced transitional cell cancer of the bladder, all of whom had progressed after being given platinum based chemotherapy for metastatic cancer.⁴ Subjects were given 350mg/m² initially, later reduced to 320mg/m². Nine patients had a partial response, with three experiencing fatal neutropoenic sepsis, and 30 and 37% of patients suffering grade 3 and 4 neutropoenia respectively.

A trial has also been carried out in patients with metastatic breast cancer which has progressed following treatment with anthracycline/taxane based therapy.⁵ Single doses of 320mg/m² were given every three weeks; again neutropoenia was the major side-effect. Eight patients had a partial response.

Vinflunine is also being investigated in combination with cisplatin.⁶ A group of untreated patients with advanced NSCLC were given 80mg/m² cisplatin, along with 250, 280 or 320mg/m² vinflunine. Absence of dose limiting toxicities at the lower doses led to 320mg/m² being chosen as the optimum dose. Five of the 15 evaluable patients had a partial response, and seven stable disease.