Mouth pain/irritation was reported in approximately 14% of patients. The above events were not cumulative, were typically reversible and generally did not result in treatment discontinuation.
Haemorrhage and tumour bleeding
Haemorrhagic events, some of which were fatal, reported through post-marketing experience, have included gastro-intestinal, respiratory, tumour, urinary tract and brain haemorrhages. In clinical trials treatment-related tumour haemorrhage occurred in approximately 2% of patients with GIST. These events may occur suddenly, and in the case of pulmonary tumours, may present as severe and life-threatening haemoptysis or pulmonary haemorrhage. Fatal pulmonary haemorrhage occurred in 2 patients (~ 1.8%) receiving sunitinib on a phase 2 clinical trial of patients with metastatic non-small cell lung cancer (NSCLC). Both patients had squamous cell histology. SUTENT is not approved for use in patients with NSCLC.
Bleeding events occurred in 18% of patients receiving sunitinib in a phase 3 GIST Study compared to 17% of patients receiving placebo. In patients receiving sunitinib for treatment-naïve MRCC, 39% had bleeding events compared to 11% of patients receiving IFN- α. Eleven (3.1%) patients on sunitinib versus 1 (0.3%) of patients on IFN-α experienced Grade 3 or greater treatment-related bleeding events. Of patients receiving sunitinib for cytokine-refractory MRCC, 26% experienced bleeding. Bleeding events, excluding epistaxis, occurred in 19% of patients receiving sunitinib in the phase 3 pNET study compared to 4% of patients receiving placebo. Routine assessment of this event should include complete blood counts and physical examination.
Epistaxis was the most common haemorrhagic adverse reaction, having been reported for approximately half of the patients with solid tumours who experienced haemorrhagic events. Some of the epistaxis events were severe, but very rarely fatal.
Gastrointestinal disorders
Nausea, diarrhoea, stomatitis, dyspepsia and vomiting were the most commonly reported gastrointestinal adverse reactions (see section 4.8).
Supportive care for gastrointestinal adverse reactions requiring treatment may include medicinal products with an anti-emetic or anti-diarrhoeal properties.
Serious, sometimes fatal gastrointestinal complications including gastrointestinal perforation have occurred rarely in patients with intra-abdominal malignancies treated with sunitinib. Treatment-related fatal gastrointestinal bleeding occurred in 0.5% of patients receiving placebo in the GIST Phase 3 study.
Hypertension
Treatment-related hypertension was reported in approximately 16% of patients with solid tumours. The dose of sunitinib was reduced or its administration temporarily suspended in approximately 2.7% of the patients who experienced hypertension. In none of these patients sunitinib was permanently discontinued. Severe hypertension (>200 mmHg systolic or 110 mmHg diastolic) occurred in 4.7% of patients with solid tumours. Treatment-related hypertension was reported in approximately 30% of patients receiving sunitinib for treatment-naïve MRCC compared to 6% of patients receiving IFN-α. Severe hypertension occurred in 12% of treatment-naïve patients on sunitinib and 6% of patients on IFN-α. Treatment-related hypertension was rep