Letrozole Versus Observation in Patients With Newly Diagnosed Uterine Leiomyosarcoma

Letrozole is an aromatase inhibitor. Aromatase is the enzyme that produces estrogen in
post-menopausal women. By interfering with the production of estrogen triggered by aromatase,
letrozole reduces the total amount of estrogen in the body. As a result, less estrogen can
reach cancer cells, thus preventing their growth.

Before you can start treatment on this study, you will have "screening tests." These tests
will help the doctor decide if you are eligible to take part in this study. These exams,
tests, or procedures are part of regular cancer care and may be done even if you do not join
the study. If you have had some of them recently, they may not need to be repeated. This will
be up to your study doctor.

Your complete medical history will be recorded, and you will have a physical exam (including
a pelvic exam). Your vital signs and blood pressure will be measured. Blood (about 2-3
teaspoons) will be drawn for routine tests. You will also have a blood test (1 teaspoon) to
check your cholesterol. You will have an electrocardiogram (ECG -- a test that measures the
electrical activity of the heart). You will also have a chest x-ray, and either a computed
tomography (CT) scan or a magnetic resonance imaging (MRI) to check the status of the
disease. Your doctors will test previously collected tumor tissue to learn if the estrogen
receptor is positive or negative.

If you are found to be eligible to take part in this study, you will be randomly assigned (as
in the toss of a coin) to 1 of 2 groups. Group 1 will receive letrozole by mouth once a day.
Group 2 will receive no treatment. Both groups will be followed closely every 3 months. You
will have an equal chance of being placed in either group.

If you are in Group 1, you will take letrozole by mouth every day for 12 weeks. Every 12
weeks is considered a study "cycle." You will only be given the amount of drug needed for 1
cycle of therapy at a time. You will keep a diary during the study that will list when and
how much drug you took. This diary will be reviewed after each cycle of therapy by the
research nurse or doctor and filed in your chart.

Every 12 weeks, all participants will have blood (about 3-4 teaspoons) drawn for routine
tests. CT scan of the chest, abdomen (stomach area), and pelvis will be done every 24 weeks.
In addition, all participants will have a physical exam (including a pelvic exam), and your
vital signs and blood pressure will be measured.

You may remain on study for as long as you are benefitting. You will be taken off study if
intolerable side effects occur.

Once you are off study, blood (about 2-3 teaspoons) will be drawn for routine tests and to
measure your cholesterol level. You will have a physical exam (including a pelvic exam), and
an MRI or CT scan.

This is an investigational study. Letrozole is approved by the FDA for treatment of some
breast cancer patients after surgery. Its use in patients with leiomyosarcoma is
experimental. Up to 80 patients will take part in this study. All will be enrolled at M. D.
Anderson.

Inclusion Criteria:

1. Patients must have signed an approved informed consent.

2. Histologically confirmed uterine leiomyosarcoma with disease limited to the uterus
(determined by surgical staging or radiologic imaging).

3. Tumors must express ER positivity by immunohistochemistry (ER expression >10% by
immunohistochemistry).

4. Patients must have a hysterectomy and bilateral oophorectomy prior to initiation of
therapy.

5. All patients must have no measurable disease. Measurable disease is defined as lesions
that can be measured by physical examination or by means of imaging techniques.
Imaging must be done within 6 weeks of study entry.

6. Patients must have a Zubrod performance status of 0, 1, or 2.

7. Patients must have a pretreatment granulocyte count (i.e., segmented neutrophils +
bands) of greater than 1,000/Fl, a hemoglobin level of greater than or equal to 9.0
gm/dL and a platelet count of greater than 75,000/dL.

8. Patients must have an adequate renal function as documented by serum creatinine less
than or equal to 2.0 mg/dL.

9. Patients must have adequate hepatic function as documented by a serum bilirubin less
than or equal to 2.5 mg/dL.

10. Aspartate transaminase (SGOT) must be less than 3x institutional upper limit of
normal.

11. Patients must have recovered from the effects of prior surgery.

12. No more than 12 weeks must have elapsed from hysterectomy.

13. Patients must be 18 years or older.

Exclusion Criteria:

1. Patients who do not have pure uterine sarcomas (i.e., no mixed malignant Mullerian
tumors).

2. Patients with any other severe concurrent disease, which would make the patient
inappropriate for entry into this study, including significant hepatic, renal, or
gastrointestinal diseases.

3. Patients with a history of prior malignancy except for adequately treated basal cell
or squamous cell skin cancer, in situ cervical cancer, or other cancer for which the
patient has been disease-free for at least five years.

4. Patients who were taking or have a history of taking letrozole or another aromatase
inhibitor.

5. Patients with active or uncontrolled systemic infection.

6. Patients with history of uncontrolled cardiac disease; i.e., uncontrolled
hypertension, unstable angina, recent myocardial infarction (within prior 6 months),
uncontrolled congestive heart failure, and cardiomyopathy with an ejection fraction
under 40%.

7. Patients who are pregnant or breast-feeding.

8. Presence of clinically apparent untreated central nervous system metastases.

9. Presence of carcinomatous meningitis.

10. Patients currently receiving chemotherapy or radiation therapy.