- Aust Prescr 2011;34:119-23
- 1 August 2011
- DOI: 10.18773/austprescr.2011.065
Some of the views expressed in the following notes on newly approved products should be regarded as preliminary, as there may have been limited published data at the time of publication, and little experience in Australia of their safety or efficacy. However, the Editorial Executive Committee believes that comments made in good faith at an early stage may still be of value. Before new drugs are prescribed, the Committee believes it is important that more detailed information is obtained from the manufacturer's approved product information, a drug information centre or some other appropriate source.
Javlor (Pierre Fabre Medicament)
vials containing 50 mg/2 mL, 100 mg/4 mL or 250 mg/10 mL
Approved indication: bladder cancer
Australian Medicines Handbook section 14.1.8
Vinflunine is indicated for advanced or metastatic transitional cell carcinoma of the urothelial tract. It is intended as a second-line treatment for patients whose disease has progressed despite platinum-containing therapy. The median survival of these patients is four months and currently treatment focuses on best supportive care.
Vinflunine is a vinca alkaloid. Like other drugs in this class, it works by binding to tubulin and inhibiting its polymerisation into microtubules. This ultimately leads to mitotic arrest and apoptosis of the cell.
In early phase II trials, patients who had progressing or recurring disease after treatment with a platinum-containing regimen were given intravenous vinflunine 320 mg/m2 every three weeks. Of the 202 patients treated, 31 (15%) had a partial response and 89 (44%) had stable disease. The median progression-free survival was 2.8-3 months and overall survival was 6.6-8.2 months.1,2
In a larger phase III comparative trial, 370 patients were randomised to receive best supportive care with or without vinflunine (320 mg/m2 every three weeks). Although the median survival was longer for patients receiving vinflunine compared to those receiving supportive care alone (6.9 months vs 4.6 months), the difference was not statistically significant (p=0.287). However, a post hoc analysis suggested a possible treatment effect (p=0.04). Significantly more people responded to vinflunine than to supportive care alone - 8.6% vs 0% had a partial response and 46.5% vs 27.1% had stable disease. Also, the median duration of disease control was significantly longer for vinflunine than for supportive care alone (5.7 vs 4.2 months), as was progression-free survival (3 vs 1.5 months). The median duration of treatment with vinflunine was 9.5 weeks. This was similar in the control group.3
Myelosuppression is a considerable problem with vinflunine. Approximately half of the 450 patients in the trials developed severe (grades 3-4) neutropenia or leucopenia. Anaemia and thrombocytopenia were also common but, in general, less severe. Infections were frequent and seven patients died from an infection that was a complication of neutropenia. Recent or current infection is a contraindication to vinflunine use. Complete blood counts should be measured before each infusion and the dose may need to be reduced or stopped if the patient has signs of toxicity.
Gastrointestinal symptoms are frequent with vinflunine. Severe constipation (15.3%) and ileus (2.2%) occurred in some patients and dose reduction was required. Alopecia (28.7%) and peripheral sensory neuropathy (9.8%) were also frequently reported.
Cardiovascular effects have occurred with vinflunine and it should be used with caution in patients with a pre-existing heart condition. One patient died of myocardial infarction and another of cardiopulmonary arrest. Vinflunine may prolong the QT interval and concomitant use of drugs that prolong the QT interval should be avoided.
Vinflunine should be given as an intravenous infusion. Accidental intrathecal use of this class of drug has been fatal. After infusion, vinflunine is extensively distributed in the tissues. It is metabolised by cytochrome P450 3A4 and excreted in the faeces and urine. The dose of vinflunine should be reduced in patients aged 75 and over, and in those with impaired liver (mild to moderate) or kidney function (moderate to severe). Vinflunine is not recommended in severe hepatic impairment. Concomitant use of drugs that inhibit or induce CYP 3A4 should be avoided.
Although vinflunine is indicated for second-line treatment of advanced bladder cancer, patients and their doctors have to consider whether the potential modest increase in life expectancy is worth the risk of developing severe adverse effects. A review of vinflunine from a French drug bulletin concluded that in practice 'it is better to focus on individually tailored palliative care'.4
manufacturer provided the AusPAR and the product information
The Transparency Score () is explained in New drugs: transparency', Vol 37 No 1, Aust Prescr 2014;37:27.
At the time the comment was prepared, a scientific discussion about this drug was available on the website of the European Medicines Agency (www.emea.europa.eu).
At the time the comment was prepared, information about this drug was available on the website of the Therapeutic Goods Administration (www.tga.gov.au/industry/pm-auspar.htm).