Simplified phenotyping of CYP2D6 for tamoxifen treatment using the N-desmethyl-tamoxifen/ endoxifen ratio.

Introduction: CYP2D6 protein activity can be inferred from the ratio of N-desmethyl-tamoxifen (NDMT) to endoxifen (E). CYP2D6 polymorphisms are common and can affect CYP2D6 protein activity and E level. Some retrospective studies indicate that E < 16 nM may relate to worse outcome.

Tamoxifen-induced severe hot flashes and endoxifen levels: is dose reduction a safe and effective strategy?

Objectives: Severe hot flash (HF) toxicity due to tamoxifen can compromise compliance. We previously found that HFs did not correlate with endoxifen level or CYP2D6 genotype. In this study, we reduced tamoxifen dose in patients with severe HFs to determine whether HFs were ameliorated whilst maintaining a purported therapeutic endoxifen level of >15 nM.

Fulvestrant for hormone-sensitive metastatic breast cancer.

Background: Fulvestrant is a selective oestrogen receptor down-regulator (SERD), which by blocking proliferation of breast cancer cells, is an effective endocrine treatment for women with hormone-sensitive advanced breast cancer. The goal of such systemic therapy in this setting is to reduce symptoms, improve quality of life, and increase survival time.

Objectives: To assess the efficacy and safety of fulvestrant for hormone-sensitive locally advanced or metastatic breast cancer in postmenopausal women, as compared to other standard endocrine agents.

Features and management of pyrexia with combined dabrafenib and trametinib in metastatic melanoma.

The combination of dabrafenib and trametinib (CombiDT) is an effective treatment for BRAF-mutant metastatic melanoma; however, over 70% of patients develop drug-related pyrexia, and little is known about this toxicity. We sought to examine the features and management of CombiDT pyrexia. The association between pyrexia and patient demographics, disease characteristics and outcome variables was assessed in patients treated with CombiDT at a single institution.