Breast Cancer, Drug Toxicity, Hormone Changes
Conditions
Keywords
drug/agent toxicity by tissue/organ, hormone changes, stage I breast cancer, stage II breast cancer
Brief summary
RATIONALE: Drugs used in chemotherapy work in different ways to stop tumor cells from dividing so they stop growing or die. Chemoprotective drugs, such as triptorelin, may protect normal ovarian cells from the side effects of chemotherapy. PURPOSE: This randomized phase II trial is studying how well triptorelin works in preserving ovarian function in premenopausal women who are receiving chemotherapy for early-stage breast cancer.
Detailed description
OBJECTIVES: Primary * Determine the protective effect of chemical ovarian suppression using triptorelin on the preservation of ovarian function in premenopausal women with early-stage operable breast cancer undergoing adjuvant or neoadjuvant systemic chemotherapy. Secondary * Determine the rate of chemotherapy-related amenorrhea in patients treated with this drug. * Determine the value of inhibin A and B as alternative markers of premature ovarian failure in patients treated with this drug. * Determine quality of life of patients treated with this drug. * Determine disease-free and overall survival of patients treated with this drug. OUTLINE: This is a randomized, multicenter study. Patients are stratified according to age (\< 35 years vs 35 to 39 years vs \> 39 years); concurrent neoadjuvant or adjuvant systemic chemotherapy (fluorouracil, epirubicin, and cyclophosphamide \[6 courses\] OR fluorouracil, doxorubicin, and cyclophosphamide \[6 courses\] vs doxorubicin and cyclophosphamide \[AC\] \[4 courses\] vs doxorubicin and cyclophosphamide \[AC\] \[4 courses\] followed by a taxane \[4 courses\]); and hormone receptor status (estrogen receptor \[ER\]- AND progesterone receptor \[PR\]-negative vs ER- OR PR-positive). * Arm I: Beginning within 1-4 weeks before the start of chemotherapy, patients receive triptorelin intramuscularly once monthly for 4-6 months during neoadjuvant or adjuvant systemic chemotherapy. * Arm II: Patients receive neoadjuvant or adjuvant systemic chemotherapy only. Quality of life is assessed at baseline, monthly during treatment, every 6 months for 2 years, and then annually for 3 years. Patients are followed every 6 months for 2 years and then annually for 3 years. PROJECTED ACCRUAL: A total of 138 patients (69 per treatment arm) will be accrued for this study within 35 months.
Interventions
DRUGtriptorelin
3.75 mg TRELSTAR DEPOT (triptorelin) administered monthly as single intramuscular injection
Sponsors
National Cancer Institute (NCI)
University of South Florida
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
SUPPORTIVE_CARE
Masking
NONE
Eligibility
Sex/Gender
FEMALE
Age
No minimum to 44 Years
Healthy volunteers
No
Inclusion criteria
DISEASE CHARACTERISTICS: * Histologically confirmed breast cancer * Early-stage, operable disease * Scheduled to receive adjuvant or neoadjuvant systemic chemotherapy for breast cancer * Hormone receptor status: * Meets 1 of the following criteria: * Estrogen receptor (ER)- OR progesterone receptor (PR)-positive * ER- AND PR-negative * No history of premature ovarian failure PATIENT CHARACTERISTICS: Age * Under 45 Sex * Female Menopausal status * Premenopausal * Follicle-stimulating hormone levels \< 40 IU/L at baseline AND at least 2 menstrual periods within the past 6 months * No first-degree relative menopausal at \< 40 years of age Performance status * Eastern Cooperative Oncology Group \[ECOG\] 0-1 Life expectancy * Not specified Hematopoietic * Not specified Hepatic * Not specified Renal * Not specified Other * Not pregnant or nursing * Fertile patients must use effective non-hormonal methods of contraception * No prior osteoporosis or other non-malignant systemic disease that would preclude prolonged follow-up * No known allergies to gonadotrophin-releasing hormone agonists * No other cancer except nonmelanoma skin cancer PRIOR CONCURRENT THERAPY: Biologic therapy * Not specified Chemotherapy * See Disease Characteristics * No prior chemotherapy Endocrine therapy * At least 2 weeks since prior oral contraceptives * No prior fertility treatment * Clomiphene or pergonal for polycystic ovarian disease allowed * No other concurrent oral or transdermal hormonal therapy, including any of the following: * Estrogen * Progesterone * Androgens * Aromatase inhibitors * Hormone replacement therapy * Oral contraceptives Radiotherapy * No prior ovarian radiotherapy Surgery * No prior bilateral oophorectomy * No plans for oophorectomy or hysterectomy within the next 2 years Other * At least 1 week since prior warfarin
Exclusion criteria
* History of premature ovarian failure * Over 45 years of age * First-degree relative menopausal at \< 40 years of age * Pregnant or nursing * Prior osteoporosis or other non-malignant systemic disease that would preclude prolonged follow-up * Known allergies to gonadotrophin-releasing hormone agonists * Other cancer besides nonmelanoma skin cancer * Prior chemotherapy * Prior ovarian radiotherapy * Prior bilateral oophorectomy
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Time to Resumption of Menses | Baseline, end of chemotherapy then 5 years | Ovarian function as assessed by follicle stimulating hormone (FSH) and record of menses every 6 months beginning in month 6 for 2 years and then annually for 3 years |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Chemotherapy-related Amenorrhea | Baseline, end of chemotherapy then 5 years | Chemotherapy-related amenorrhea as assessed by record of menses monthly during treatment. Record of menses is completed by patient throughout their time on study through chemotherapy and for 5 years. |
Countries
United States
Participant flow
Recruitment details
49 female patients were enrolled between July 2003 and January 2007.
Participants by arm
| Arm | Count |
|---|---|
| Triptorelin GnRH analogue (triptorelin) during chemotherapy | 27 |
| no Triptorelin no GnRH analogue (triptorelin) during chemotherapy | 22 |
| Total | 49 |
Baseline characteristics
| Characteristic | Triptorelin | no Triptorelin | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 27 Participants | 22 Participants | 49 Participants |
| Age, Continuous | 39 years | 38 years | 39 years |
| Ethnicity (NIH/OMB) Hispanic or Latino | 3 Participants | 2 Participants | 5 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 24 Participants | 20 Participants | 44 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 2 Participants | 2 Participants |
| Race (NIH/OMB) Black or African American | 2 Participants | 1 Participants | 3 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 25 Participants | 19 Participants | 44 Participants |
| Region of Enrollment United States | 27 participants | 22 participants | 49 participants |
| Sex: Female, Male Female | 27 Participants | 22 Participants | 49 Participants |
| Sex: Female, Male Male | 0 Participants | 0 Participants | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 25 / 27 | 18 / 22 |
| serious Total, serious adverse events | 2 / 27 | 0 / 22 |
Outcome results
Primary
Time to Resumption of Menses
Ovarian function as assessed by follicle stimulating hormone (FSH) and record of menses every 6 months beginning in month 6 for 2 years and then annually for 3 years
Time frame: Baseline, end of chemotherapy then 5 years
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Triptorelin | Time to Resumption of Menses | 4.96 months |
| no Triptorelin | Time to Resumption of Menses | 5.82 months |
Secondary
Chemotherapy-related Amenorrhea
Chemotherapy-related amenorrhea as assessed by record of menses monthly during treatment. Record of menses is completed by patient throughout their time on study through chemotherapy and for 5 years.
Time frame: Baseline, end of chemotherapy then 5 years
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Triptorelin | Chemotherapy-related Amenorrhea | 3 Participants |
| no Triptorelin | Chemotherapy-related Amenorrhea | 2 Participants |