Sunitinib malate

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.

Sutent (Pfizer)
12.5 mg, 25 mg and 50 mg capsules
Approved indications: gastrointestinal stromal tumour, renal cell carcinoma
Australian Medicines Handbook section 14.3.9

Tyrosine kinase inhibitors, such as imatinib, interfere with the angiogenesis that is required for tumour growth (see 'Angiogenesis inhibitors in cancer', Aust Prescr 2006;29:9-12, Aust Prescr 2006;29:13-5). Sunitinib (SU11248) acts on multiple receptor tyrosine kinases, including a tyrosine kinase which is associated with gastrointestinal stromal tumours. Its anti-angiogenic effects may give it a role in vascular tumours such as renal cell carcinoma.

In an open-label phase II trial, 63 patients were treated with sunitinib after their metastatic renal cell carcinoma had progressed despite immunotherapy. The median duration of treatment was nine months. The investigators' assessment of tumour images found that 25 patients had a partial response to treatment. The median time to further progression of the tumours was 8.7 months with a median survival of 16.4 months.¹

Another open-label phase II study included 106 patients with metastatic clear cell renal cell carcinoma after immunotherapy had failed. They were treated for about seven months. Independent assessments found that 36 patients achieved a partial response. The median duration of response and median survival had not been reached when the data were analysed. After six months 79% of the patients were still alive.²

Gastrointestinal stromal tumours are sarcomas that usually occur in the stomach or small bowel. Before the development of imatinib, surgery was the only effective treatment but was not always possible. A placebo-controlled trial has investigated giving sunitinib after treatment with imatinib fails. Interim analysis showed a partial response in 14 of the 207 patients randomised to take sunitinib and none of the 105 patients in the placebo group. The time to disease progression was 27.3 weeks with sunitinib and 6.4 weeks with placebo. As this difference could contribute to improved survival all the patients in the placebo group were switched to sunitinib.

The recommended regimen for sunitinib is a daily dose of 50 mg for four weeks followed by a two-week break before repeating the cycle. The dose can be taken with or without a meal as food has no effect on bioavailability. Sunitinib and its active metabolite are metabolised by cytochrome P450 3A4. Dose reductions should be considered if the patient is taking an inhibitor of this enzyme. The dose of sunitinib may need to be increased if an enzyme-inducing drug is prescribed. Patients taking sunitinib should not take St John's wort because of this interaction. The half-life of sunitinib is 40-60 hours with most of the metabolites being excreted in the faeces. There have been no studies of sunitinib in patients with impaired hepatic or renal function.

In the trials, fatigue, diarrhoea, dyspepsia, nausea and vomiting were common adverse events. Discolouration of the skin or hair, and rashes, particularly on the palms and soles, were also frequently reported. Hypertension developed in 25% of previously untreated patients with renal cancer and 33% reported bleeding. Reductions in platelets and blood cell counts are very common. Many patients will also develop abnormal biochemical and liver function tests. Sunitinib can prolong the QT interval and cause left ventricular dysfunction. Deep venous thrombosis and pulmonary embolism have also been reported. As sunitinib has been associated with adrenal toxicity in animal studies, patients experiencing stress, such as surgery, should be monitored for adrenal insufficiency. Approximately 4% of patients develop hypothyroidism.

The evidence shows that sunitinib is likely to be of benefit to some patients with gastrointestinal stromal tumours who have not responded to imatinib or cannot tolerate it. However, these tumours are uncommon so only a limited number of people will benefit.

Advanced renal cell carcinoma has a poor prognosis. Sunitinib may improve this, but the results need to be confirmed in randomised phase III studies. Preliminary data suggest that there may be a greater response to sunitinib than to immunotherapy with interferon alfa.³

manufacturer provided the clinical evaluation

The Transparency Score ( ) is explained in New drugs: transparency', Vol 37 No 1, Aust Prescr 2014;37:27.

Notes on references

At the time the comment was prepared, information about this drug was available on the web site of the Food and Drug Administration in the USA (www.fda.gov).

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).