Aromatase inhibitors: side effects reported by 622 women.

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Aromatase inhibitors: side effects reported by 622 women.

Salgado BA, Zivian MT.. Breast Cancer Action, San Francisco, CA

http://www.bcaction.org/PDF/AIReport.pdf for complete survey results

Background: Aromatase inhibitors (anastrozole, letrozole, and exemestane) are

quickly becoming one of the most commonly prescribed breast cancer treatments

for postmenopausal women with breast cancer. Because these drugs have only

been approved for use recently, and two of the three aromatase inhibitors moved

quickly into the treatment setting due to FDA Priority Review or Accelerated

Approval status, little is known about their short and long-term side effects.

Previous trials of aromatase inhibitors have reported some adverse effects.

The purpose of this survey is to collect information from patients on the side

effects of aromatase inhibitors.

Methods: An Aromatase Inhibitor Side Effects Survey (AI Survey) was posted to

the Breast Cancer Action web site in August 2005. Additionally, other breast

cancer and womens health organizations announced the AI survey through

newsletters, emails and web site links. Despite the limitations and biases that

self-reporting introduces, patient-derived data on treatment side effects are

clinically meaningful for both doctors and patients. The survey included

demographic questions, questions concerning the aromatase inhibitor prescribed,

and

questions regarding medical condition. These were followed by a list of 38 side

effects that respondents rated for severity. The surveys side effects list was

compiled from side effects listed on the FDA labels for aromatase inhibitors.

Respondents were also asked if they had experienced any unlisted side effects.

Over 600 completed surveys were received and included in the data set. Data

were analyzed using SPSS (Version 14.0 for Windows).

Results: The distribution of the survey respondents from the United States

reflects the expected distribution based on of the incidence of breast cancer

throughout the country (p < .01). Among the women who discontinued using an AI,

exemestane was taken for a significantly shorter period of time (8 months)

than either letrozole (15 months) or anastrazole (29 months) (p = .002). Over

60%

of the respondents reported experiencing stroke and cough. Over 50% reported

swelling of limbs, and flu-like symptoms. Women 30-39 years-old gave the

highest severity ratings to stroke; women 50-59 years-old women gave highest

severity ratings to cough (p < .000). In addition to reporting on the side

effects

listed in the survey, respondents reported experiencing over 35 additional side

effects.

Discussion: Recent advances have led to the development of aromatase

inhibitors for adjuvant treatment of postmenopausal breast cancer patients.

However,

many patients are experiencing adverse effects which can be disabling and may

lead to cessation of therapy. Patients and doctors should discuss possible side

effects before beginning treatment with aromatase inhibitors so that patients

are able to make fully informed decisions. The side effects information from

this survey will also assist doctors with patient management for those

currently taking aromatase inhibitors.

From BCAction

About Aromatase Inhibitors

Aromatase inhibitors are a type of hormone therapy for postmenopausal women

with breast cancer. AIs prevent the aromatase enzyme from converting the

hormone androgen into estrogen. Produced by the adrenal gland and found

throughout

the body, androgen is the principal source of estrogen for postmenopausal

women. AIs have only been approved for use by postmenopausal women. They are

ineffective in premenopausal women whose ovaries are still producing estrogen

(which

is not affected by the aromatase enzyme). None of these drugs has been

approved by the FDA for use by healthy women at high risk of developing breast

cancer.

Three AIs are currently approved by the FDA for the treatment of breast

cancer in postmenopausal women: anastrozole (Arimidex), exemestane (Aromasin),

and

letrozole (Femara). Anastrozole and letrozole are both nonsteroidal aromatase

inhibitors. Th ey are described as reversible because they bind reversibly to

the aromatase enzyme.

Exemestane is a steroidal inhibitor that forms an irreversible bond with the

aromatase enzyme, permanently stopping the activity of the enzyme.

Anastrozole (Arimidex)

Arimidex is indicated for adjuvant treatment of postmenopausal women with

hormone-receptor-positive early breast cancer.

Arimidex is indicated for the fi rst-line treatment of postmenopausal women

with hormone-receptor-positive or hormone-receptor-unknown locally advanced or

metastatic breast cancer.

Arimidex is indicated for the treatment of advanced breast cancer in

postmenopausal women with disease progression following tamoxifen therapy.

Exemestane (Aromasin)

Aromasin is indicated for adjuvant treatment of postmenopausal women with

estrogen-receptor-positive early breast cancer who have received two to three

years of tamoxifen and are switched to Aromasin for completion of a total of fi

ve consecutive years of adjuvant hormonal therapy.

Aromasin is indicated for the treatment of advanced breast cancer in

postmenopausal women whose disease has progressed following tamoxifen therapy.

Letrozole (Femara)

Femara is indicated for the adjuvant treatment of postmenopausal women with

hormone-receptor-positive early breast cancer.

Femara is indicated for the extended adjuvant treatment of early breast

cancer in postmenopausal women who have received fi ve years of adjuvant

tamoxifen

therapy.

Femara is indicated for fi rst-line treatment of postmenopausal women with

hormone-receptor-positive or hormone-receptor-unknown locally advanced or

metastatic breast cancer.

Femara is also indicated for the treatment of advanced breast cancer in

postmenopausal women with disease progression following anti-estrogen therapy.

Summary of Findings

The first 612 completed surveys received were analyzed for this report. Major

findings include:

1. Most respondents (96%) reported one or more side effects.

2. The side effects reported by over 50% of respondents were: stroke (65%),

cough (64%), swelling of the arms and legs (59%), fl u-like symptoms (58%), and

anxiety (51%).

3. Many women reported side effects in addition to those on our list,

including joint-related side effects, vaginal atrophy and dryness, a rise in

cholesterol levels, and general pain.

4. Over 50% of respondents stated that their menopause was not naturally

occurring. For these women, menopause was either pharmaceutically or surgically

induced.

5. Ten women (1.6%) reported that they discontinued using an AI because of

subsequent menstruation or vaginal bleeding.

6. About 30% of the respondents discontinued the use of an AI & shy;84% because

of side effects they were experiencing, and close to half of them (47%)

specifically because of joint-related side effects.

7. Over one-third (37%) of respondents reported receiving no information from

their doctors about short-term side effects; nearly two-thirds (63%) reported

receiving no information from their doctors about long-term side effects.

Recommendations

1. Conduct additional research on short-term and long-term side effects of

AIs.

2. Provide the results of this research to doctors and patients.

3. Use caution when prescribing AIs to perimenopausal women, as well as to

premenopausal women who have been rendered menopausal by chemotherapy or ovarian

function suppression.