Plain English Summary
Not provided at time of registration
Trial website
Contact information
Type
Scientific
Primary contact
Dr Prasert Lertsaguansinchai
ORCID ID
Contact details
Department of Radiology
Wongwanich Building
Chulalongkorn University Hospital
Rama IV Street
Pratumwam
Bangkok
10330
Thailand
+66 22564590, 91203311, 4736842
Prasert@chularcancer.net
Additional identifiers
EudraCT number
ClinicalTrials.gov number
Protocol/serial number
CFEM345DTH01
Study information
Scientific title
Acronym
LOTUS trial
Study hypothesis
Letrozole is more effective than tamoxifen in first line treatment of metastatic breast cancer.
In advanced disease, letrozole has been associated with significantly more tumor regression than anastrozole, especially in patients with unknown ER status. Letrozole has also been shown to be more effective than tamoxifen in the neoadjuvant treatment of breast cancer. Recently, anastrozole has been shown to induce a reduction in the rate of relapse as compared with tamoxifen in the adjuvant setting. Extended adjuvant therapy with letrozole after 5 years tamoxifen has been demonstrated to reduce the risk of recurrence and to improve significantly the diseasefree survival of postmenopausal women with early breast cancer. International studies are investigating the effect of letrozole compared to tamoxifen in the adjuvant treatment of early breast cancer patients. Few Asian patients are included. A large number of early breast cancer patients in Thailand are currently being treated with tamoxifen as adjuvant treatment.
It is not yet clear whether aromatase inhibitor can replace tamoxifen as adjuvant treatment for early breast cancer. Sequence and timing of tamoxifen and aromatase inhibitor treatment in adjuvant treatment still needs to be determined as well.
The goals of this study are the following:
1. To determine whether the replacement, as adjuvant therapy, of tamoxifen by letrozole for the last 3 years of a standard 5 year treatment period can reduce the risk of treatment failure in early breast cancer patients
2. To conduct this study in a Thai population
3. To compare the 2 treatments in terms of safety and tolerability
Approximately 1000 patients from up to 15 centers across Thailand will be enrolled into this study. The patient population will include postmenopausal women with resected Stage I, II, or IIIa, ER+ and/or PR+ breast cancer who have received 2 years of adjuvant tamoxifen and who have no clinical or radiological evidence of recurrent or metastatic disease before randomization. Pre-menopausal women who are/become amenorrheic due to either chemotherapy or Luteinizing Hormone Releasing Hormone (LHRH) use may participate in the study. Patients must have undergone complete tumor resection and margins of the resected specimen must be microscopically free of tumor.
Ethics approval
Not provided at time of registration
Study design
Open-label, Randomized Study
Primary study design
Interventional
Secondary study design
Randomised controlled trial
Trial setting
Hospitals
Trial type
Treatment
Patient information sheet
Condition
ER positive and/or PR positive early breast cancer
Intervention
After providing consent, patients will be screened for eligibility.
Eligible patients will be registered at any time up to 2 years (+/- 3 months) of tamoxifen treatment. Tamoxifen treatment had to be started at a dose of 20 mg/day for 2 years. After that, patients event-free will be randomly assigned to continue receiving tamoxifen for an additional 3 years or receiving letrozole 2.5 mg/day for 3 years.
After completion of treatment, patients should be followed up for study end points for 3 years.
Intervention type
Drug
Phase
Not Specified
Drug names
Letrozole, tamoxifen
Primary outcome measure
Compare these treatment regimens in terms of disease free survival (DFS)
Secondary outcome measures
1. Compare these treatment regimens in terms of overall survival (OS)
2. Compare these treatment regimens in terms of safety and tolerability in the Thai patient population
Overall trial start date
01/01/2005
Overall trial end date
31/12/2012
Reason abandoned (if study stopped)
Eligibility
Participant inclusion criteria
1. Patients with stage I, II or IIIa adenocarcinoma of the breast at diagnosis. Patients with breast cancer whose tumor has been completely removed macroscopically and margins of the resected tumor have been microscopically free of tumor. If appropriate, additional local (e.g. radiotherapy) and/or systemic (i.e. adjuvant chemotherapy) treatments are allowed.
2. Postmenopausal status defined by one of the following:
a. Age ≥55 years with cessation of menses
b. Age <55 but no spontaneous menses for at least 1 year
c. 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
d. Bilateral oophorectomy
3. Patients whose tumors are either ER+ and/or PR+ (defined as ER and/or PR ≥10 fmol/mg cytosol protein; or ≥10% of the tumor cells positive by immunohistochemical evaluation)
4. Under tamoxifen therapy for 2 years before randomization
5. At randomization, patients must have no clinical or radiological evidence of distant metastasis, and no other concomitant malignancy (confirmed by mammography, chest X-ray or computed tomography [CT] scan, bone scan and liver US)
6. Eastern Cooperative Oncology Group (ECOG) performance status of 02
7. No prior treatment with letrozole
8. Patients must be accessible for follow-up
9. Signed written informed consent
Participant type
Patient
Age group
Adult
Gender
Female
Target number of participants
1000
Participant exclusion criteria
1. Patients with any clinical or radiological evidence of distant spread of their disease at any point before randomization
2. Patients with other non-malignant systemic diseases including uncontrolled infections, uncontrolled type 2 diabetes mellitus, uncontrolled thyroid dysfunction, cardiovascular, renal, hepatic, and lung diseases which would prevent prolonged follow-up. Patients with previous history of thrombosis or thromboembolism can be included only if medically suitable. Patients with a known history of human immunodeficiency virus (HIV) are excluded.
3. Total serum calcium >2.75 mmol/l (11.0 mg/dl)
4. White Blood Cell Count (WBC) <3.0 x 10^9/l or granulocytes <1.5 x 10^9/l, platelets <100 x 10^9/l
5. Aspartate amino transferase (AST)/serum glutamic oxaloacetic transaminase (SGOT) and/or alanine amino transferase (ALT)/serum glutamic pyruvic transaminase (SGPT) >3 upper limit of normal (ULN) in combination with other laboratory and clinical abnormalities indicating liver insufficiency to a degree that precludes dosing with letrozole (Child-Pugh grade C)
6. Patients with abnormal renal function as defined by a serum creatinine ≥3 mg/dl (265.2 mmol/l)
7. Previous history of fracture within 2 years
8. Patients treated with other systemic investigational drug(s) and/or device(s) within the past 30 days
9. History of non-compliance to medical regimens and patients who are considered potentially unreliable
10. Mental illness that precludes the patient from giving informed consent
Recruitment start date
01/01/2005
Recruitment end date
31/12/2012
Locations
Countries of recruitment
Thailand
Trial participating centre
Department of Radiology
Bangkok
10330
Thailand
Sponsor information
Organisation
Thai Breast Cancer Study Group (Thailand)
Sponsor details
Department of Radiation Oncology
Chulalongkorn University Hospital
Rama 4 Street. Pratumwan
Bangkok
10330
Thailand
+66 22564590, 91203311, 4736842
Prasert@chularcancer.net
Sponsor type
Other
Website
Funders
Funder type
Industry
Funder name
Partially sponsored by Novartis Thailand
Alternative name(s)
Funding Body Type
Funding Body Subtype
Location
Results and Publications
Publication and dissemination plan
Not provided at time of registration
Intention to publish date
Participant level data
Not provided at time of registration
Basic results (scientific)
Publication list