- Title
- A randomized, double-blind, placebo-controlled study of high-dose bosentan in patients with stage IV metastatic melanoma receiving first-line dacarbazine chemotherapy
- Creator
- Kefford, Richard F.; Clingan, Philip R.; Brady, Benjamin; Ballmer, Andrea; Morganti, Adele; Hersey, Peter
- Relation
- Molecular Cancer Vol. 9, Issue 69
- Publisher Link
- http://dx.doi.org/10.1186/1476-4598-9-69
- Publisher
- BioMed Central
- Resource Type
- journal article
- Date
- 2010
- Description
- Background: The endothelin system is implicated in the pathogenesis of melanoma. We evaluated the effects of bosentan - a dual endothelin receptor antagonist - in patients receiving first-line dacarbazine therapy for stage IV metastatic cutaneous melanoma in a phase 2, proof-of-concept study. Results: Eligible patients had metastatic cutaneous melanoma naïve to chemotherapy or immunotherapy, no central nervous system involvement, and serum lactate dehydrogenase <1.5 × upper limit of normal. Treatment comprised bosentan 500 mg twice daily or matching placebo, in addition to dacarbazine 1000 mg/m² every three weeks. Eighty patients were randomized (double-blind) and 38 in each group received study treatment. Median time to tumor progression (primary endpoint) was not significantly different between the two groups (placebo, 2.8 months; bosentan, 1.6 months; bosentan/placebo hazard ratio, 1.144; 95% CI, 0.717-1.827; p = 0.5683). Incidences of most adverse events and clinically relevant increases in hepatic transaminases were similar between treatment groups although hemoglobin decrease to >8 and ≤ 10 g/dL and ≤ 8 g/dL was more common in the bosentan group. Conclusions: In patients receiving dacarbazine as first-line chemotherapy for metastatic melanoma, the addition of high-dose bosentan had no effect on time to tumor progression or other efficacy parameters. There were no unexpected safety findings. Trial registration: This study is registered in ClinicalTrials.gov under the unique identifier NCT01009177.
- Subject
- pulmonary arterial-hypertension; endothelin-receptor antagonist; phase III trial; malignant melanoma
- Identifier
- http://hdl.handle.net/1959.13/923433
- Identifier
- uon:9730
- Identifier
- ISSN:1476-4598
- Language
- eng
- Full Text
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