Letrozole in the Treatment of Advanced or Recurrent Hormone Receptor Positive Endometrial Cancer (deFEND)

Inclusion Criteria:

• Signed informed consent
• Age > 18 years
• Presence of histologically proven adenocarcinoma or adenosquamous carcinoma of the endometrium
• Presence of advanced or recurrent endometrial cancer, FIGO stage I-IV, incurable with surgery and/or radiation therapy
• Documented ER and/or PgR positive endometrial cancer. Hormone receptor positivity is defined according to routine practice at each participating laboratory.

• Patient must be postmenopausal defined as

  • Age ≥55 years.
  • Age <55 but no spontaneous menses for at least 1 year.
  • Age <55 and spontaneous menses within the past 1 year, but currently amenorrheic (e.g., spontaneous or secondary to hysterectomy), and with postmenopausal gonadotrophin levels (luteinizing hormone and follicle stimulating hormone levels >40 IU/L) or postmenopausal estradiol levels (<5 ng/dL) or according to the definition of "postmenopausal range" for the laboratory involved.
  • Bilateral oophorectomy
  • Radiation menopause
• Presence of measurable disease (by clinical/radiological examination - according to RECIST criteria : minimum indicator lesion size : 20 mm (unless spiral CT scan in which case > 10 mm)
• ECOG performance status of 0, 1 or 2
• Adequate bone marrow function (WBC ≥ 3.5 x 1'000'000'000/L and platelets ≥ 100.0 x 1'000'000'000/L) and hemoglobin > 10.0 g/dl
• Adequate renal function (creatinine < 120 µmol/L) and hepatic function (bilirubin < 25 µmol/L, AST (SGOT < 60 U/L)
• Minimum life expectancy of at least 6 months
• Patients who are accessible for treatment and follow-up

Exclusion Criteria:

• Presence of non-measurable disease only
• Other concomitant anti-cancer treatment (except external radiation treatment [XRT] for symptomatic metastatic lesions if other assessable untreated lesions are present)
• Prior treatment with aromatase inhibitors or anti-estrogens (up to one previous progestational hormone therapy regimen for recurrent disease is permitted)
• Clear cell or papillary serous histology, uterine sarcomas, mixed Mullerian tumors (MMT) and/or adenosarcomas
• Other concurrent malignant disease with the exception of cone-biopsied in situ carcinoma of the cervix uteri, or adequately treated basal or squamous cell carcinoma of the skin, or other curable cancers e.g. Hodgkin`s disease or non-Hodgkin lymphoma (NHL), provided 5 years have elapsed from completion of therapy, and there has been no recurrence
• Known central nervous system (CNS) metastases, bilateral diffuse lymphangiosis carcinoma of the lung (>50 % of lung involvement, or dyspnea at rest requiring supplemental oxygen therapy), evidence of metastases estimated as more than a third of the liver as defined by sonogram and/or CT scan
• Uncontrolled endocrine disorders such as diabetes mellitus, confirmed hypo- or hyperthyroidism, Cushing`s Syndrome, Addison`s disease (treated or untreated)
• Unstable angina and uncontrolled cardiac disease
• Treatment with other investigational drugs (drugs not marketed for any indication) within the past 30 days and/or the concomitant use of investigational drugs
• A history of non-compliance to medical regimens and patients who, in the opinion of the investigator, are unlikely to cooperate fully during the study
• Inability to swallow pills

Additional protocol-defined inclusion/exclusion criteria may apply.