Breast Cancer
Conditions
Keywords
breast cancer, stage I breast cancer, stage II breast cancer, stage IIIA breast cancer, stage IIIB breast cancer, stage IIIC breast cancer, stage IV breast cancer, breast cancer in situ, ductal breast carcinoma in situ
Brief summary
RATIONALE: Chemoprevention therapy is the use of certain drugs to try to prevent the development or recurrence of cancer. Letrozole may be effective in preventing the development or recurrence of breast cancer in postmenopausal women who are at increased risk of developing breast cancer because of elevated estradiol levels. PURPOSE: This randomized phase II trial is studying how well letrozole works in preventing breast cancer in postmenopausal women with elevated estradiol levels.
Detailed description
OBJECTIVES: Primary * The primary outcome of the study is the change in bone mineral density following a year on letrozole vs. a year on placebo. Secondary * Compare the safety, acceptability, and adherence to letrozole vs placebo in postmenopausal women at increased risk for the development or recurrence of breast cancer based on elevated plasma estradiol levels through evaluation of menopausal symptoms (including hot flushes, weight changes, sexual functioning, and genitourinary effects), blood lipid levels, markers of bone turnover, and multidimensional quality of life. * Determine the effect of letrozole-induced reduction of plasma estradiol levels on mammographic percent breast density. * Obtain background information for a future large chemoprevention trial to address the question of whether a reduction in plasma estradiol levels can reduce the risk of breast cancer in postmenopausal women. OUTLINE: This is a pilot, randomized, double-blind, placebo-controlled, multicenter study. Patients are randomized to 2:1 (experimental treatment: placebo arms). PROJECTED ACCRUAL: A total of 110 patients (73 for arm I and 37 for arm II) will be accrued for this study.
Interventions
DRUGLetrozole
OTHERPlacebo
Sponsors
National Cancer Institute (NCI)
Jonsson Comprehensive Cancer Center
Dana-Farber Cancer Institute
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
FEMALE
Age
35 Years to 120 Years
Healthy volunteers
No
Inclusion criteria
DISEASE CHARACTERISTICS: * At increased risk for the development or recurrence of breast cancer, defined as an estradiol level ≥ 9 pg/mL * No evidence of suspicious or malignant disease, based on the following examinations: * Clinical bilateral breast examination within the past 6 months * Bilateral\* mammogram within 3 months before randomization OR within 30 days after randomization * Pelvic exam normal within the past 5 years * General physical exam within the past 6 months NOTE: \*Unilateral mammogram of the uninvolved breast for patients with prior invasive breast cancer or ductal carcinoma in situ (DCIS) * Bone density scan within 2 standard deviations from normal within the past 30 days * Bone density scan ≥ 2 standard deviations below normal allowed if approved by the study physician * At least 1 breast that has not been previously treated with radiotherapy or surgery (for patients with prior invasive breast cancer or DCIS) * Hormone receptor status: * Not specified PATIENT CHARACTERISTICS: Age * 35 and over Sex * Female Menopausal status * Postmenopausal, defined by any of the following criteria: * At least 12 months without spontaneous menstrual bleeding * Prior hysterectomy and bilateral salpingo-oophorectomy * ≥ 55 years of age with a prior hysterectomy with or without oophorectomy * \< 55 years of age with a prior hysterectomy without oophorectomy OR the status of the ovaries is unknown AND follicle-stimulating hormone (FSH) level is in the postmenopausal range Performance status * Normal activity must not be restricted for a significant portion of the day Life expectancy * At least 10 years Hematopoietic * Complete blood count with differential normal * Prior benign neutropenia allowed provided the granulocyte count is ≥ 1,500/mm\^3 Hepatic * Bilirubin normal * Alkaline phosphatase normal * SGOT and SGPT normal Renal * Creatinine normal Cardiovascular * No uncontrolled cardiovascular disease Other * Not pregnant * No other malignancy within the past 5 years except basal cell or squamous cell skin cancer or carcinoma in situ of the cervix * No osteoporosis * No hyperlipidemia * No mental health status resulting in cognitive or emotional impairment that would preclude study participation PRIOR CONCURRENT THERAPY: Biologic therapy * Not specified Chemotherapy * Not specified Endocrine therapy * More than 30 days since prior AND no concurrent use of any of the following hormonal agents: * Estrogen or progesterone replacement therapy * Oral contraceptives * Raloxifene or other plasma estrogen receptor modulators (SERMs) * Androgens (e.g., danazol) * Luteinizing hormone-releasing hormone (LHRH) analogs (e.g., goserelin or leuprolide) * Prolactin inhibitors (e.g., bromocriptine) * Antiandrogens (e.g., cyproterone) * More than 60 days since prior AND no concurrent tamoxifen * No prior aromatase inhibitors (for patients with prior invasive breast cancer or DCIS) * No concurrent phytoestrogenic dietary supplements (e.g., soy, ginseng, or other natural products) * Dietary soy allowed Radiotherapy * See Disease Characteristics Surgery * See Disease Characteristics * No prior bilateral mastectomy Other * More than 60 days since prior treatment for invasive breast cancer or DCIS * More than 30 days since prior bisphosphonates or calcitonin * No prior or concurrent participation on a treatment study for invasive breast cancer or DCIS * No concurrent participation in any other cancer prevention study or osteoporosis prevention study involving pharmacologic agents * No concurrent calcitonin * No concurrent bisphosphonate therapy * Concurrent cholecalciferol (vitamin D) and calcium to augment bone mineral density allowed
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in Lumbar Density From Baseline to 12 Months | Evaluation occurred at treatment initiation (BL) and after 12-months of treatment. | The bone mineral density (BMD) test was comprised of the following 4 measurements \[total density (g/cm\^2)\]: lumbar, femoral neck, trochanter, hip. |
| Change in Femoral Neck Density From Baseline to 12 Months | Evaluation occurred at treatment initiation (BL) and after 12-months of treatment. | The bone mineral density (BMD) test was comprised of the following 4 measurements \[total density (g/cm\^2)\]: lumbar, femoral neck, trochanter, hip. |
| Change in Trochanter Density From Baseline to 12 Months | Evaluation occurred at treatment initiation (BL) and after 12-months of treatment. | The bone mineral density (BMD) test was comprised of the following 4 measurements \[total density (g/cm\^2)\]: lumbar, femoral neck, trochanter, hip. |
| Change in Hip Density From Baseline to 12 Months | Evaluation occurred at treatment initiation (BL) and after 12-months of treatment. | The bone mineral density (BMD) test was comprised of the following 4 measurements \[total density (g/cm\^2)\]: lumbar, femoral neck, trochanter, hip. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Worst Grade Abdominal Pain | Heath assessments during treatment were administered at 3- and 9-months by telephone contact and during clinic visits at 6- and12-months. | Participants reported worst grade abdominal pain: 01: mild, 02: moderate, 03: severe (CTCAEv3), 04: disabling (CTCAEv3) during 12 months of treatment. |
| Worst Grade Bone Pain | Heath assessments during treatment were administered at 3- and 9-months by telephone contact and during clinic visits at 6- and12-months. | Participants reported worst grade bone pain: 01: mild, 02: moderate, 03: severe (CTCAEv3), 04: disabling (CTCAEv3) during 12 months of treatment. |
| Worst Grade Hot Flashes | Heath assessments during treatment were administered at 3- and 9-months by telephone contact and during clinic visits at 6- and12-months. | Participants reported worst grade hot flashes: 01: mild (\<1qd) or 02: moderate (\>1qd) during 12 months of treatment. |
| Worst Grade Fatigue | Heath assessments during treatment were administered at 3- and 9-months by telephone contact and during clinic visits at 6- and12-months. | Participants reported worst grade fatigue: 01: mild, 02: moderate, 03: severe (CTCAEv3), 04: disabling (CTCAEv3) during 12 months of treatment. |
| Worst Grade Headache | Heath assessments during treatment were administered at 3- and 9-months by telephone contact and during clinic visits at 6- and12-months. | Participants reported worst grade headache: 01: mild, 02: moderate, 03: severe (CTCAEv3), 04: disabling (CTCAEv3) during 12 months of treatment. |
| Worst Grade Muscle Aches/Pains | Heath assessments during treatment were administered at 3- and 9-months by telephone contact and during clinic visits at 6- and12-months. | Participants reported worst grade muscle aches/pains defined as grade 01: mild, 02: moderate, 03: severe (CTCAEv3) or 04: disabling (CTCAEv3) during 12 months of treatment. |
| Worst Grade Nausea | Heath assessments during treatment were administered at 3- and 9-months by telephone contact and during clinic visits at 6- and12-months. | Participants reported worst grade nausea grade 01: able to eat, 02: oral intake significantly decreased, 03: no significant intake, requiring IV fluids during 12 months of treatment. |
| Worst Grade Vomiting | Heath assessments during treatment were administered at 3- and 9-months by telephone contact and during clinic visits at 6- and12-months. | Participants reported worst grade vomiting grade 01: 1x in 24 hours, 02: 2-5x in 24 hours, 03: \>/= 6x in 24 hours, grade 04: requiring parenteral nutrition/intensive care during 12 months of treatment. |
Countries
United States
Participant flow
Recruitment details
Patients enrolled from February 2002 through August 2007.
Pre-assignment details
In this chemoprevention trial, postmenopausal women were screened and eligible based on serum estradiol levels. Of 405 women screened, 381 were eligible for blood draw. Of these 381 women eligible for blood draw, 87 were eligible for randomization based on serum estradiol level (\>/=0.9 ng/dL). There were 38 women who declined to be randomized.
Participants by arm
| Arm | Count |
|---|---|
| Letrozole Participants in this arm received 2.5 mg of letrozole per day for a duration of 12 months; followed by an optional 4 years. Treatment continued in the absence of unacceptable toxicity or diagnosis of invasive breast cancer, ductal carcinoma in situ, or any non-breast primary cancer. | 33 |
| Placebo Participants in this arm received 1 tablet per day which contained the inert ingredients from the letrozole tablet, for a duration of 12 months; followed by an optional 5 years of letrozole.Treatment continued in the absence of unacceptable toxicity or diagnosis of invasive breast cancer, ductal carcinoma in situ, or any non-breast primary cancer. | 16 |
| Total | 49 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 2 | 2 |
| Overall Study | Lost to Follow-up | 0 | 1 |
| Overall Study | Withdrawal by Subject | 2 | 0 |
Baseline characteristics
| Characteristic | Letrozole | Placebo | Total |
|---|---|---|---|
| Age, Continuous | 56 years | 52.5 years | 54 years |
| Region of Enrollment United States | 33 participants | 16 participants | 49 participants |
| Sex: Female, Male Female | 33 Participants | 16 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 | 0 / 33 | 0 / 16 |
| other Total, other adverse events | 6 / 33 | 2 / 16 |
| serious Total, serious adverse events | 1 / 33 | 0 / 16 |
Outcome results
Primary
Change in Femoral Neck Density From Baseline to 12 Months
The bone mineral density (BMD) test was comprised of the following 4 measurements \[total density (g/cm\^2)\]: lumbar, femoral neck, trochanter, hip.
Time frame: Evaluation occurred at treatment initiation (BL) and after 12-months of treatment.
Population: The analysis dataset is comprised of randomized patients with an evaluable sample for analysis of femoral neck density.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Letrozole | Change in Femoral Neck Density From Baseline to 12 Months | -0.0065 g/cm^2 |
| Placebo | Change in Femoral Neck Density From Baseline to 12 Months | -0.013 g/cm^2 |
Comparison: Sample size for a detectable difference in the within participant change in bone density between arms was calculated using standard deviations of one year change in bone density. Control estimates were 2.8% for spine and 3.85% for femoral neck. With 100 patients and 2:1 randomization (67 letrozole: 33 placebo), using a 1-sided Wilcoxon rank sum test with size 0.05, there is 80% power to detect as significant a true difference in change in the spine of 1.6% and in the femoral neck of 2.27%.p-value: 0.7Wilcoxon (Mann-Whitney)
Primary
Change in Hip Density From Baseline to 12 Months
The bone mineral density (BMD) test was comprised of the following 4 measurements \[total density (g/cm\^2)\]: lumbar, femoral neck, trochanter, hip.
Time frame: Evaluation occurred at treatment initiation (BL) and after 12-months of treatment.
Population: The analysis dataset is comprised of randomized patients with an evaluable sample for analysis of hip density.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Letrozole | Change in Hip Density From Baseline to 12 Months | -0.0275 g/cm^2 |
| Placebo | Change in Hip Density From Baseline to 12 Months | -0.001 g/cm^2 |
Comparison: Sample size for a detectable difference in the within participant change in bone density was calculated using standard deviations of one year change in bone density. Control estimates were 2.8% for spine and 3.85% for femoral neck. With 100 patients and 2:1 randomization (67 letrozole: 33 placebo), using a 1-sided Wilcoxon rank sum test with size 0.05, there is 80% power to detect as significant a true difference in change in the spine of 1.6% and in the femoral neck of 2.27%.p-value: 0.06Wilcoxon (Mann-Whitney)
Primary
Change in Lumbar Density From Baseline to 12 Months
The bone mineral density (BMD) test was comprised of the following 4 measurements \[total density (g/cm\^2)\]: lumbar, femoral neck, trochanter, hip.
Time frame: Evaluation occurred at treatment initiation (BL) and after 12-months of treatment.
Population: The analysis dataset is comprised of randomized patients with an evaluable sample for analysis of lumbar density.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Letrozole | Change in Lumbar Density From Baseline to 12 Months | -0.036 g/cm^2 |
| Placebo | Change in Lumbar Density From Baseline to 12 Months | -0.021 g/cm^2 |
Comparison: Sample size for a detectable difference in the within participant change in bone density between arms was calculated using standard deviations of one year change in bone density. Control estimates were 2.8% for spine and 3.85% for femoral neck. With 100 patients and 2:1 randomization (67 letrozole: 33 placebo), using a 1-sided Wilcoxon rank sum test with size 0.05, there is 80% power to detect as significant a true difference in change in the spine of 1.6% and in the femoral neck of 2.27%.p-value: 0.15Wilcoxon (Mann-Whitney)
Primary
Change in Trochanter Density From Baseline to 12 Months
The bone mineral density (BMD) test was comprised of the following 4 measurements \[total density (g/cm\^2)\]: lumbar, femoral neck, trochanter, hip.
Time frame: Evaluation occurred at treatment initiation (BL) and after 12-months of treatment.
Population: The analysis dataset is comprised of randomized patients with an evaluable sample for analysis of trochanter density.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Letrozole | Change in Trochanter Density From Baseline to 12 Months | -0.017 g/cm^2 |
| Placebo | Change in Trochanter Density From Baseline to 12 Months | -0.009 g/cm^2 |
Comparison: Sample size for a detectable difference in the within participant change in bone density between arms was calculated using standard deviations of one year change in bone density. Control estimates were 2.8% for spine and 3.85% for femoral neck. With 100 patients and 2:1 randomization (67 letrozole: 33 placebo), using a 1-sided Wilcoxon rank sum test with size 0.05, there is 80% power to detect as significant a true difference in change in the spine of 1.6% and in the femoral neck of 2.27%.p-value: 0.03Wilcoxon (Mann-Whitney)
Secondary
Worst Grade Abdominal Pain
Participants reported worst grade abdominal pain: 01: mild, 02: moderate, 03: severe (CTCAEv3), 04: disabling (CTCAEv3) during 12 months of treatment.
Time frame: Heath assessments during treatment were administered at 3- and 9-months by telephone contact and during clinic visits at 6- and12-months.
Population: The analysis dataset is comprised of all randomized participants.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Letrozole | Worst Grade Abdominal Pain | None | 27 Participants |
| Letrozole | Worst Grade Abdominal Pain | Mild | 3 Participants |
| Letrozole | Worst Grade Abdominal Pain | Missing | 3 Participants |
| Placebo | Worst Grade Abdominal Pain | None | 16 Participants |
| Placebo | Worst Grade Abdominal Pain | Mild | 0 Participants |
| Placebo | Worst Grade Abdominal Pain | Missing | 0 Participants |
p-value: 0.27Fisher Exact
Secondary
Worst Grade Bone Pain
Participants reported worst grade bone pain: 01: mild, 02: moderate, 03: severe (CTCAEv3), 04: disabling (CTCAEv3) during 12 months of treatment.
Time frame: Heath assessments during treatment were administered at 3- and 9-months by telephone contact and during clinic visits at 6- and12-months.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Letrozole | Worst Grade Bone Pain | None | 22 Participants |
| Letrozole | Worst Grade Bone Pain | Mild | 2 Participants |
| Letrozole | Worst Grade Bone Pain | Moderate | 6 Participants |
| Letrozole | Worst Grade Bone Pain | Missing | 3 Participants |
| Placebo | Worst Grade Bone Pain | Missing | 0 Participants |
| Placebo | Worst Grade Bone Pain | None | 12 Participants |
| Placebo | Worst Grade Bone Pain | Moderate | 1 Participants |
| Placebo | Worst Grade Bone Pain | Mild | 3 Participants |
p-value: 0.6Fisher Exact
Secondary
Worst Grade Fatigue
Participants reported worst grade fatigue: 01: mild, 02: moderate, 03: severe (CTCAEv3), 04: disabling (CTCAEv3) during 12 months of treatment.
Time frame: Heath assessments during treatment were administered at 3- and 9-months by telephone contact and during clinic visits at 6- and12-months.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Letrozole | Worst Grade Fatigue | None | 19 Participants |
| Letrozole | Worst Grade Fatigue | Mild | 6 Participants |
| Letrozole | Worst Grade Fatigue | Moderate | 5 Participants |
| Letrozole | Worst Grade Fatigue | Missing | 3 Participants |
| Placebo | Worst Grade Fatigue | Missing | 0 Participants |
| Placebo | Worst Grade Fatigue | None | 11 Participants |
| Placebo | Worst Grade Fatigue | Moderate | 3 Participants |
| Placebo | Worst Grade Fatigue | Mild | 2 Participants |
p-value: 0.49Fisher Exact
Secondary
Worst Grade Headache
Participants reported worst grade headache: 01: mild, 02: moderate, 03: severe (CTCAEv3), 04: disabling (CTCAEv3) during 12 months of treatment.
Time frame: Heath assessments during treatment were administered at 3- and 9-months by telephone contact and during clinic visits at 6- and12-months.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Letrozole | Worst Grade Headache | Missing | 3 Participants |
| Letrozole | Worst Grade Headache | Mild | 7 Participants |
| Letrozole | Worst Grade Headache | None | 20 Participants |
| Letrozole | Worst Grade Headache | Moderate | 3 Participants |
| Placebo | Worst Grade Headache | None | 11 Participants |
| Placebo | Worst Grade Headache | Missing | 0 Participants |
| Placebo | Worst Grade Headache | Moderate | 2 Participants |
| Placebo | Worst Grade Headache | Mild | 3 Participants |
p-value: 0.58Fisher Exact
Secondary
Worst Grade Hot Flashes
Participants reported worst grade hot flashes: 01: mild (\<1qd) or 02: moderate (\>1qd) during 12 months of treatment.
Time frame: Heath assessments during treatment were administered at 3- and 9-months by telephone contact and during clinic visits at 6- and12-months.
Population: The analysis dataset is comprised of all randomized participants.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Letrozole | Worst Grade Hot Flashes | None | 14 Participants |
| Letrozole | Worst Grade Hot Flashes | Mild (<1 qd) | 5 Participants |
| Letrozole | Worst Grade Hot Flashes | Moderate | 11 Participants |
| Letrozole | Worst Grade Hot Flashes | Missing | 3 Participants |
| Placebo | Worst Grade Hot Flashes | Missing | 0 Participants |
| Placebo | Worst Grade Hot Flashes | None | 9 Participants |
| Placebo | Worst Grade Hot Flashes | Moderate | 4 Participants |
| Placebo | Worst Grade Hot Flashes | Mild (<1 qd) | 3 Participants |
p-value: 0.38Fisher Exact
Secondary
Worst Grade Muscle Aches/Pains
Participants reported worst grade muscle aches/pains defined as grade 01: mild, 02: moderate, 03: severe (CTCAEv3) or 04: disabling (CTCAEv3) during 12 months of treatment.
Time frame: Heath assessments during treatment were administered at 3- and 9-months by telephone contact and during clinic visits at 6- and12-months.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Letrozole | Worst Grade Muscle Aches/Pains | Moderate | 7 Participants |
| Letrozole | Worst Grade Muscle Aches/Pains | Missing | 3 Participants |
| Letrozole | Worst Grade Muscle Aches/Pains | Severe | 1 Participants |
| Letrozole | Worst Grade Muscle Aches/Pains | None | 14 Participants |
| Letrozole | Worst Grade Muscle Aches/Pains | Mild | 8 Participants |
| Placebo | Worst Grade Muscle Aches/Pains | Mild | 2 Participants |
| Placebo | Worst Grade Muscle Aches/Pains | None | 13 Participants |
| Placebo | Worst Grade Muscle Aches/Pains | Missing | 0 Participants |
| Placebo | Worst Grade Muscle Aches/Pains | Moderate | 1 Participants |
| Placebo | Worst Grade Muscle Aches/Pains | Severe | 0 Participants |
p-value: 0.02Fisher Exact
Secondary
Worst Grade Nausea
Participants reported worst grade nausea grade 01: able to eat, 02: oral intake significantly decreased, 03: no significant intake, requiring IV fluids during 12 months of treatment.
Time frame: Heath assessments during treatment were administered at 3- and 9-months by telephone contact and during clinic visits at 6- and12-months.
Population: The analysis dataset is comprised of all randomized participants.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Letrozole | Worst Grade Nausea | None | 23 Participants |
| Letrozole | Worst Grade Nausea | Able to Eat | 5 Participants |
| Letrozole | Worst Grade Nausea | Oral Intake Significantly Decreased | 1 Participants |
| Letrozole | Worst Grade Nausea | Missing | 4 Participants |
| Placebo | Worst Grade Nausea | Missing | 0 Participants |
| Placebo | Worst Grade Nausea | None | 15 Participants |
| Placebo | Worst Grade Nausea | Oral Intake Significantly Decreased | 0 Participants |
| Placebo | Worst Grade Nausea | Able to Eat | 1 Participants |
p-value: 0.2Fisher Exact
Secondary
Worst Grade Vomiting
Participants reported worst grade vomiting grade 01: 1x in 24 hours, 02: 2-5x in 24 hours, 03: \>/= 6x in 24 hours, grade 04: requiring parenteral nutrition/intensive care during 12 months of treatment.
Time frame: Heath assessments during treatment were administered at 3- and 9-months by telephone contact and during clinic visits at 6- and12-months.
Population: The analysis dataset is comprised of all randomized participants.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Letrozole | Worst Grade Vomiting | None | 28 Participants |
| Letrozole | Worst Grade Vomiting | 1x in 24 hours | 1 Participants |
| Letrozole | Worst Grade Vomiting | 2-5x in 24 hours | 0 Participants |
| Letrozole | Worst Grade Vomiting | Missing | 4 Participants |
| Placebo | Worst Grade Vomiting | Missing | 0 Participants |
| Placebo | Worst Grade Vomiting | None | 15 Participants |
| Placebo | Worst Grade Vomiting | 2-5x in 24 hours | 1 Participants |
| Placebo | Worst Grade Vomiting | 1x in 24 hours | 0 Participants |
p-value: 0.88Fisher Exact