A phase II study of bosentan, a dual endothelin receptor antagonist, as monotherapy in patients with stage IV metastatic melanoma

Thirty-five patients with stage IV metastatic melanoma were enrolled in this open-label, single-arm, prospective, multicentre trial. The objective was to assess the effects of bosentan monotherapy (500 mg oral tablets, twice daily) given as first- or second-line therapy on tumour response. Patients were followed up until disease progression, death or drug toxicity occurred. Tumour response was assessed at 6-weekly intervals using the Response Evaluation Criteria in Solid Tumours (RECIST). Results: The study population (n = 35) had a median age of 61.0 years (32–79) and an American Joint Committee on Cancer (AJCC) class of M1C (n = 21, 60.0%), M1B (n = 10, 28.6%) and M1A (n = 4, 11.4%). Nine patients (25.7%) had prior therapy for stage IV melanoma. Stable disease (SD) was observed in 6/35 patients at week 12, 5 of whom (M1A = 2, M1C = 2, M1B = 1) were stable at >_24 weeks. Five of the 6 patients with SD received bosentan as first-line therapy. Bosentan was well tolerated; it was discontinued due to adverse events in only 7/35 patients, one of whom had progressive disease at the same time. The most frequent adverse events were headache (n = 15, 42.9%), fatigue (n = 12, 34.3%), nausea (n = 11, 31.4%), back pain and abnormal hepatic function (both n = 8, 22.9%). Conclusions: Bosentan is well tolerated and may have benefit in disease stabilization in patients with metastatic melanoma. Further studies to evaluate bosentan as first-line treatment may be warranted.