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Breast Cancer

The Clinical Pharmacology of Anastrozole Ting Bao1

and Michelle A Rudek2

1. Assistant Professor, University of Maryland Marlene and Stewart Greenebaum Cancer Center, University of Maryland School of Medicine; 2. Laboratory Scientist, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine


Anastrozole is a potent non-steroidal aromatase inhibitor that selectively inhibits aromatase. It is the first aromatase inhibitor approved by the US Food and Drug Administration as an adjuvant hormonal therapy in early-stage breast cancer. With most patients needing to take anastrozole for two to five years, it is important for physicians to understand the clinical pharmacology of anastrozole. Anastrozole has excellent oral bioavailability and is widely distributed throughout the body. It is extensively metabolised by the liver, with a half-life of 40–50 hours. Anastrozole is primarily excreted through the faecal route. Steady-state concentrations are achieved after seven days of once-daily administration. The standard dosage of anastrozole is 1mg/day orally. No dose adjustments are necessary based on hepatic or renal dysfunction. No significant drug–drug interaction has been reported with anastrozole use. This article is to summarise the existing knowledge of the pharmacokinetics of anastrozole.

Keywords Anastrozole, pharmacokinetics, aromatase inhibitor, breast carcinoma, oestrogen, post-menopausal

Disclosure: The authors have no conflicts of interest to declare. Received: 15 March 2010 Accepted: 10 September 2010 Citation: European Oncology & Haematology, 2011;7(2):106–8 Correspondence: Ting Bao, 22 S Greene Street, Baltimore, MD 21201, US. E:

Breast cancer is the most common cancer and the second most common cause of cancer death among women in the US.1

resulted in significant side effects.12,13 It is

estimated that two-thirds of the invasive breast cancers will be hormone-receptor-positive and will require long-term adjuvant hormonal therapy.

In addition, multiple clinical trials have shown that AIs have superior efficacy compared with tamoxifen as an adjuvant hormonal therapy in post-menopausal women with hormone-receptor-positive breast cancer.6–11

Reducing the effect of oestrogen is the main aim of hormonal therapy in treating hormone-receptor-positive breast cancer. The effect of oestrogen is reduced in two ways – by blocking the oestrogen receptor or by inhibiting oestrogen biosynthesis. The mechanism of action of aromatase inhibitors (AIs) is to inhibit oestrogen biosynthesis. AIs have established their role in treating metastatic hormone-receptor-positive breast cancer in post-menopausal women through a number of clinical trials.2–5

AIs are therefore the recommended first-line adjuvant hormonal therapy in post-menopausal women with hormone-receptor-positive breast cancer, either as monotherapy or as sequential therapy after tamoxifen.

The recommended duration of adjuvant AI therapy is usually two to five years. With the recommended treatment period being up to five years in the adjuvant setting, it is important for physicians to understand the clinical pharmacology of some of the commonly used AIs.

Aromatase Inhibitor Development AIs have been around for over 20 years. Aminoglutethimide was the first AI in general clinical use. Its use was limited by its intermediate efficacy in inhibiting aromatisation and its low specificity, which


Roglethimide was the second

glutethimide derivative, whose use was limited by its low potency and significant side effects.14,15

The second-generation AI fadrozole was

then developed and was found to be more specific than aminoglutethimide. It still has significant side effects as it suppresses aldosterone synthesis.16,17

The third-generation AIs anastrozole,

letrozole and exemestane have been developed most recently. They are superior in both their high oestrogen biosynthesis suppression and their specificity, resulting in very few side effects.18

Among them,

anastrozole and letrozole are non-steroidal AIs, whereas exemestane is steroidal. Anastrozole was the first third-generation AI to be tested in clinical trials in treating metastatic and early-stage hormone- receptor-positive breast cancer in post-menopausal women.

The advanced role of anastrozole compared with megestrol acetate in treating advanced breast carcinoma as second-line therapy after tamoxifen has been demonstrated in a number of clinical trials.2,3


addition, a randomised clinical trial comparing anastrozole with tamoxifen as first-line therapy for patients with advanced breast cancer demonstrated that anastrozole is significantly better than tamoxifen in prolonging time to disease progression.5

Moreover, the

As a result, anastrozole was the first AI approved by the US Food and Drug Administration (FDA) as an adjuvant hormonal therapy in early-stage breast cancer in 2002.21

This article will focus on summarising the clinical pharmacology of anastrozole. © TOUCH BRIEFINGS 2011

Arimidex, Tamoxifen Alone or in Combination (ATAC) trial reported an increased disease-free survival and time to recurrence with anastrozol (Arimidex) compared with tamoxifen. It also showed an improved toxicity profile in terms of the risk of endometrial cancer and thromboembolic events in women receiving anastrozole compared with tamoxifen.19,20

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