title: Intermittent dosing with vemurafenib in BRAF V600E-mutant melanoma: review of a case series.
abstract: The selective BRAF inhibitors, vemurafenib and dabrafenib, yield high response rates and improved overall survival in patients with BRAF V600E-mutant metastatic melanoma. Acquired drug resistance and drug toxicity are key challenges when using these drugs. We investigated whether vemurafenib toxicity could successfully be managed with intermittent dosing, and if its therapeutic efficacy could be maintained on intermittent dosing. Six patients with BRAF V600E-mutated metastatic melanoma were treated with an intermittent dosing regimen of vemurafenib. In three patients, toxicities were successfully managed with an intermittent dosing regimen. In the other three patients, intolerable toxicities continued on intermittent dosing. Our experience shows that intermittent dosing can successfully manage vemurafenib toxicities where continuous dosing at a reduced dose does not. Intermittent treatment improves drug tolerability and can achieve or maintain melanoma shrinkage. We recommend that in clinical practice, intermittent dosing should be considered as an alternative to dose reduction/termination in the management of vemurafenib toxicity.
authors.affiliation: University of Oxford, John Radcliffe Hospital, Oxford, UK.
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Dooley
authors.affiliation: Department of Oncology, NIHR Biomedical Research Centre, Oxford Cancer and Haematology Centre, Churchill Hospital, Oxford, UK.
authors.forename: Avinash
authors.initials: A
authors.lastname: Gupta
authors.affiliation: Department of Oncology, Royal Berkshire Hospital, Reading, UK.
authors.forename: Madhumita
authors.initials: M
authors.lastname: Bhattacharyya
authors.affiliation: Department of Oncology, NIHR Biomedical Research Centre, Oxford Cancer and Haematology Centre, Churchill Hospital, Old Road, Headington, Oxford, OX3 7LE, UK.
authors.forename: Mark R
authors.initials: MR
authors.lastname: Middleton
keywords: intermittent; melanoma; resistance; toxicity; vemurafenib