Breast Carcinoma
Conditions
Brief summary
This randomized pilot clinical trial studies topical cryotherapy (cooling hands and feet with ice bags) in reducing pain in patients with chemotherapy induced peripheral neuropathy or paclitaxel induced acute pain syndrome. Peripheral neuropathy is a nerve problem that causes pain, numbness, tingling, swelling, or muscle weakness in different parts of the body. Paclitaxel produces a disabling syndrome of acute aches and pains. Topical cryotherapy is being studied to see if it can help relieve pain from peripheral neuropathy or acute pain syndrome caused by chemotherapy.
Detailed description
PRIMARY OBJECTIVES: I. To estimate whether topical cryotherapy can alleviate paclitaxel-induced peripheral neuropathy. II. To estimate whether topical cryotherapy can alleviate paclitaxel-induced acute pain syndrome (P-APS). III. To examine the possible relative toxicities related to topical cryotherapy in this study situation. OUTLINE: Patients are randomized to 1 of 2 arms. ARM I: Patients apply bags filled with crushed ice to hands and feet for 15 minutes before, for 60 minutes during administration, and for 15 minutes after finishing administration of paclitaxel. ARM II: Patients receive paclitaxel intravenously (IV) over 60 minutes on weeks 1-12. In both arms, courses repeat once a week for 12 weeks in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed up every 30 days for 6 months.
Interventions
PROCEDURECryotherapy
Applied topically
DRUGPaclitaxel
Given IV
OTHERQuality-of-Life Assessment
Ancillary studies
OTHERQuestionnaire Administration
Ancillary studies
Sponsors
National Cancer Institute (NCI)
Academic and Community Cancer Research United
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Ability to complete questionnaires by themselves or with assistance * Planned paclitaxel at a dose of 80 mg/m\^2 intravenously (I.V.) given, in the adjuvant breast cancer (postoperative or neo-adjuvant) setting, every week for a planned course of 12 weeks without any other concurrent cytotoxic chemotherapy (NOTE: trastuzumab and/or other antibody and/or small molecule treatment is allowed, except for poly adenosine diphosphate ribose polymerase \[PARP\] inhibitors), at the entering Academic and Community Cancer Research United (ACCRU) institution * Life expectancy \> 6 months * Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1 * Patient has score of 0 or 1 on the neurotoxicity evaluation, as determined by the healthcare provider
Exclusion criteria
* Previous diagnosis of diabetic neuropathy or peripheral neuropathy from any cause * Diagnosis of fibromyalgia * Any prior exposure to neurotoxic chemotherapy * History of Raynaud?s disease, cryoglobulinemia
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Area Under the Curve (AUC) EORTC CIPN20 Shooting/Burning Pain in Toes or Feet Item Adjusting for Baseline | Up to 12 weeks | Average Area Under the Curve per assessment (aAUCpa) of EORTC Chemotherapy-Induced Peripheral Neuropathy Module (EORTC QLQ-CIPN20) Shooting/Burning Pain in Toes or Feet over 12 weeks adjusting for baseline (item 1; During the past week, did you have shooting or burning pain in your Toes or Feet?; 1=Not at all, 2=A little, 3=Quite a bit; and 4=Very much). The reported score was transform into 0-100 scale, with higher scores represent fewer symptoms (better QOL). The aAUCpa for the individual item is calculated as the average of each AUC between each sequential assessment from pre-treatment-initiation to the week-12 assessment then subtract the corresponding baseline score, with positive scores represent symptoms has improved from baseline and negative scores represent symptoms has worsen from baseline. |
| Area Under the Curve (AUC) EORTC CIPN20 Sensory Neuropathy Subscale Adjusting for Baseline | Up to 12 weeks | Average Area Under the Curve per assessment (aAUCpa) of EORTC Chemotherapy-Induced Peripheral Neuropathy Module (EORTC QLQ-CIPN20) Sensory Neuropathy Subscale adjusting for baseline. The EORTC CIPN20 scoring algorithm was used for the sensory (items 31-36, 39, 40 and 48) subscale scores on a 0-100 scale, with higher scores represent fewer symptoms (better QOL). The aAUCpa for the subscale is calculated as the average of each AUC between each sequential assessment from pre-treatment-initiation to the week-12 assessment then subtract the corresponding baseline Sensory Neuropathy subscale score, with positive scores represent symptoms has improved from baseline and negative scores represent symptoms has worsen from baseline. |
| Area Under the Curve (AUC) EORTC CIPN20 Tingling Fingers or Hands Item Adjusting for Baseline | Up to 12 weeks | Average Area Under the Curve per assessment (aAUCpa) of EORTC Chemotherapy-Induced Peripheral Neuropathy Module (EORTC QLQ-CIPN20) Tingling Fingers or Hands over 12 weeks adjusting for baseline (item 1; During the past week, did you have tingling fingers or hands?; 1=Not at all, 2=A little, 3=Quite a bit; and 4=Very much). The reported score was transform into 0-100 scale, with higher scores represent fewer symptoms (better QOL). The aAUCpa for the individual item is calculated as the average of each AUC between each sequential assessment from pre-treatment-initiation to the week-12 assessment then subtract the corresponding baseline score, with positive scores represent symptoms has improved from baseline and negative scores represent symptoms has worsen from baseline. |
| Area Under the Curve (AUC) EORTC CIPN20 Tingling Toes or Feet Item Adjusting for Baseline | Up to 12 weeks | Average Area Under the Curve per assessment (aAUCpa) of EORTC Chemotherapy-Induced Peripheral Neuropathy Module (EORTC QLQ-CIPN20) Tingling Toes or Feet over 12 weeks adjusting for baseline (item 1; During the past week, did you have tingling toes or feet?; 1=Not at all, 2=A little, 3=Quite a bit; and 4=Very much). The reported score was transform into 0-100 scale, with higher scores represent fewer symptoms (better QOL). The aAUCpa for the individual item is calculated as the average of each AUC between each sequential assessment from pre-treatment-initiation to the week-12 assessment then subtract the corresponding baseline score, with positive scores represent symptoms has improved from baseline and negative scores represent symptoms has worsen from baseline. |
| Area Under the Curve (AUC) EORTC CIPN20 Numbness Fingers or Hands Item Adjusting for Baseline | Up to 12 weeks | Average Area Under the Curve per assessment (aAUCpa) of EORTC Chemotherapy-Induced Peripheral Neuropathy Module (EORTC QLQ-CIPN20) Numbness Fingers or Hands over 12 weeks adjusting for baseline (item 1; During the past week, did you have numbness in your fingers or hands?; 1=Not at all, 2=A little, 3=Quite a bit; and 4=Very much). The reported score was transform into 0-100 scale, with higher scores represent fewer symptoms (better QOL). The aAUCpa for the individual item is calculated as the average of each AUC between each sequential assessment from pre-treatment-initiation to the week-12 assessment then subtract the corresponding baseline score, with positive scores represent symptoms has improved from baseline and negative scores represent symptoms has worsen from baseline. |
| Area Under the Curve (AUC) EORTC CIPN20 Numbness Toes or Feet Item Adjusting for Baseline | Up to 12 weeks | Average Area Under the Curve per assessment (aAUCpa) of EORTC Chemotherapy-Induced Peripheral Neuropathy Module (EORTC QLQ-CIPN20) Numbness Toes or Feet over 12 weeks adjusting for baseline (item 1; During the past week, did you have numbness in your toes or feet?; 1=Not at all, 2=A little, 3=Quite a bit; and 4=Very much). The reported score was transform into 0-100 scale, with higher scores represent fewer symptoms (better QOL). The aAUCpa for the individual item is calculated as the average of each AUC between each sequential assessment from pre-treatment-initiation to the week-12 assessment then subtract the corresponding baseline score, with positive scores represent symptoms has improved from baseline and negative scores represent symptoms has worsen from baseline. |
| Area Under the Curve (AUC) EORTC CIPN20 Shooting/Burning Pain in Fingers or Hands Item Adjusting for Baseline | Up to 12 weeks | Average Area Under the Curve per assessment (aAUCpa) of EORTC Chemotherapy-Induced Peripheral Neuropathy Module (EORTC QLQ-CIPN20) Shooting/Burning Pain in Fingers or Hands over 12 weeks adjusting for baseline (item 1; During the past week, did you have shooting or burning pain in your fingers or hands?; 1=Not at all, 2=A little, 3=Quite a bit; and 4=Very much). The reported score was transform into 0-100 scale, with higher scores represent fewer symptoms (better QOL). The aAUCpa for the individual item is calculated as the average of each AUC between each sequential assessment from pre-treatment-initiation to the week-12 assessment then subtract the corresponding baseline score, with positive scores represent symptoms has improved from baseline and negative scores represent symptoms has worsen from baseline. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Area Under the Curve (AUC) Per Assessment (aAUCpa) of Worst Pain (Item 1 on the Daily Post-Paclitaxel Questionnaire) | 1 week | Average Area Under the Curve (AUC) per assessment (aAUCpa) of worst pain (item 1 on the Daily Post-Paclitaxel Questionnaire; Please rate any aches/pain that are new since your last dose of paclitaxel, and that you think might be related to your chemotherapy treatment, by circling ONE number that best describes your aches/pain at its WORST in the last 24 hours.) over 1 week. Scores are reported on a 0-100 scale, where 100=better outcome quality of life (QOL). The aAUCpa is the average of each AUC between each sequential assessment from day 2 through 7 following paclitaxel. |
Countries
United States
Participant flow
Recruitment details
Forty-six (46) participants were enrolled from 13 academic and community practice institutions in the United States between 12/24/2015 and June 16, 2017.
Pre-assignment details
There were three patients who withdrew consent (1 cryotherapy, 2 control) and one patient on the cryotherapy arm who was found to be ineligible. All of these 4 participants were excluded from all analyses.
Participants by arm
| Arm | Count |
|---|---|
| Arm I (Cryotherapy) Patients receive topical cryotherapy for 15 minutes prior to each paclitaxel dose, during paclitaxel infusion and for 15 minutes following paclitaxel completion. Therapy repeats every week for a planned course of 12 weeks of adjuvant paclitaxel. | 21 |
| Arm II (Control) Patients receive the standard of care only (paclitaxel at a dose of 80 mg/m2 IV) every week for a planned course of 12 weeks. | 21 |
| Total | 42 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 1 | 1 |
| Overall Study | Alternative Therapy | 1 | 1 |
| Overall Study | Chemo regimen changed after 1st Rx | 0 | 1 |
| Overall Study | Withdrawal by Subject | 2 | 1 |
Baseline characteristics
| Characteristic | Arm II (Control) | Total | Arm I (Cryotherapy) |
|---|---|---|---|
| Age, Continuous | 55.0 years | 53.0 years | 53.0 years |
| ECOG Performance Status 0 | 18 Participants | 36 Participants | 18 Participants |
| ECOG Performance Status 1 | 3 Participants | 6 Participants | 3 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 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 | 21 Participants | 42 Participants | 21 Participants |
| Region of Enrollment United States | 21 Participants | 42 Participants | 21 Participants |
| Sex: Female, Male Female | 21 Participants | 41 Participants | 20 Participants |
| Sex: Female, Male Male | 0 Participants | 1 Participants | 1 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 21 | 0 / 21 |
| other Total, other adverse events | 4 / 21 | 9 / 21 |
| serious Total, serious adverse events | 0 / 21 | 1 / 21 |
Outcome results
Primary
Area Under the Curve (AUC) EORTC CIPN20 Numbness Fingers or Hands Item Adjusting for Baseline
Average Area Under the Curve per assessment (aAUCpa) of EORTC Chemotherapy-Induced Peripheral Neuropathy Module (EORTC QLQ-CIPN20) Numbness Fingers or Hands over 12 weeks adjusting for baseline (item 1; During the past week, did you have numbness in your fingers or hands?; 1=Not at all, 2=A little, 3=Quite a bit; and 4=Very much). The reported score was transform into 0-100 scale, with higher scores represent fewer symptoms (better QOL). The aAUCpa for the individual item is calculated as the average of each AUC between each sequential assessment from pre-treatment-initiation to the week-12 assessment then subtract the corresponding baseline score, with positive scores represent symptoms has improved from baseline and negative scores represent symptoms has worsen from baseline.
Time frame: Up to 12 weeks
Population: Patients who completed the EORTC QLQ-CIPN20 at pre-treatment-initiation and at least once post-treatment initiation.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Arm I (Cryotherapy) | Area Under the Curve (AUC) EORTC CIPN20 Numbness Fingers or Hands Item Adjusting for Baseline | -5.6 Average(subscale value*assessment) |
| Arm II (Control) | Area Under the Curve (AUC) EORTC CIPN20 Numbness Fingers or Hands Item Adjusting for Baseline | -4.9 Average(subscale value*assessment) |
p-value: 0.32Wilcoxon (Mann-Whitney)
Primary
Area Under the Curve (AUC) EORTC CIPN20 Numbness Toes or Feet Item Adjusting for Baseline
Average Area Under the Curve per assessment (aAUCpa) of EORTC Chemotherapy-Induced Peripheral Neuropathy Module (EORTC QLQ-CIPN20) Numbness Toes or Feet over 12 weeks adjusting for baseline (item 1; During the past week, did you have numbness in your toes or feet?; 1=Not at all, 2=A little, 3=Quite a bit; and 4=Very much). The reported score was transform into 0-100 scale, with higher scores represent fewer symptoms (better QOL). The aAUCpa for the individual item is calculated as the average of each AUC between each sequential assessment from pre-treatment-initiation to the week-12 assessment then subtract the corresponding baseline score, with positive scores represent symptoms has improved from baseline and negative scores represent symptoms has worsen from baseline.
Time frame: Up to 12 weeks
Population: Patients who completed the EORTC QLQ-CIPN20 at pre-treatment-initiation and at least once post-treatment initiation.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Arm I (Cryotherapy) | Area Under the Curve (AUC) EORTC CIPN20 Numbness Toes or Feet Item Adjusting for Baseline | 0.0 Average(subscale value*assessment) |
| Arm II (Control) | Area Under the Curve (AUC) EORTC CIPN20 Numbness Toes or Feet Item Adjusting for Baseline | -3.2 Average(subscale value*assessment) |
p-value: 0.41Wilcoxon (Mann-Whitney)
Primary
Area Under the Curve (AUC) EORTC CIPN20 Sensory Neuropathy Subscale Adjusting for Baseline
Average Area Under the Curve per assessment (aAUCpa) of EORTC Chemotherapy-Induced Peripheral Neuropathy Module (EORTC QLQ-CIPN20) Sensory Neuropathy Subscale adjusting for baseline. The EORTC CIPN20 scoring algorithm was used for the sensory (items 31-36, 39, 40 and 48) subscale scores on a 0-100 scale, with higher scores represent fewer symptoms (better QOL). The aAUCpa for the subscale is calculated as the average of each AUC between each sequential assessment from pre-treatment-initiation to the week-12 assessment then subtract the corresponding baseline Sensory Neuropathy subscale score, with positive scores represent symptoms has improved from baseline and negative scores represent symptoms has worsen from baseline.
Time frame: Up to 12 weeks
Population: Patients who completed the EORTC QLQ-CIPN20 at pre-treatment-initiation and at least once post-treatment initiation.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Arm I (Cryotherapy) | Area Under the Curve (AUC) EORTC CIPN20 Sensory Neuropathy Subscale Adjusting for Baseline | -1.4 Average(subscale value*assessment) |
| Arm II (Control) | Area Under the Curve (AUC) EORTC CIPN20 Sensory Neuropathy Subscale Adjusting for Baseline | -4.4 Average(subscale value*assessment) |
p-value: 0.26Wilcoxon (Mann-Whitney)
Primary
Area Under the Curve (AUC) EORTC CIPN20 Shooting/Burning Pain in Fingers or Hands Item Adjusting for Baseline
Average Area Under the Curve per assessment (aAUCpa) of EORTC Chemotherapy-Induced Peripheral Neuropathy Module (EORTC QLQ-CIPN20) Shooting/Burning Pain in Fingers or Hands over 12 weeks adjusting for baseline (item 1; During the past week, did you have shooting or burning pain in your fingers or hands?; 1=Not at all, 2=A little, 3=Quite a bit; and 4=Very much). The reported score was transform into 0-100 scale, with higher scores represent fewer symptoms (better QOL). The aAUCpa for the individual item is calculated as the average of each AUC between each sequential assessment from pre-treatment-initiation to the week-12 assessment then subtract the corresponding baseline score, with positive scores represent symptoms has improved from baseline and negative scores represent symptoms has worsen from baseline.
Time frame: Up to 12 weeks
Population: Patients who completed the EORTC QLQ-CIPN20 at pre-treatment-initiation and at least once post-treatment initiation.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Arm I (Cryotherapy) | Area Under the Curve (AUC) EORTC CIPN20 Shooting/Burning Pain in Fingers or Hands Item Adjusting for Baseline | 0.0 Average(subscale value*assessment) |
| Arm II (Control) | Area Under the Curve (AUC) EORTC CIPN20 Shooting/Burning Pain in Fingers or Hands Item Adjusting for Baseline | 0.0 Average(subscale value*assessment) |
p-value: 0.76Wilcoxon (Mann-Whitney)
Primary
Area Under the Curve (AUC) EORTC CIPN20 Shooting/Burning Pain in Toes or Feet Item Adjusting for Baseline
Average Area Under the Curve per assessment (aAUCpa) of EORTC Chemotherapy-Induced Peripheral Neuropathy Module (EORTC QLQ-CIPN20) Shooting/Burning Pain in Toes or Feet over 12 weeks adjusting for baseline (item 1; During the past week, did you have shooting or burning pain in your Toes or Feet?; 1=Not at all, 2=A little, 3=Quite a bit; and 4=Very much). The reported score was transform into 0-100 scale, with higher scores represent fewer symptoms (better QOL). The aAUCpa for the individual item is calculated as the average of each AUC between each sequential assessment from pre-treatment-initiation to the week-12 assessment then subtract the corresponding baseline score, with positive scores represent symptoms has improved from baseline and negative scores represent symptoms has worsen from baseline.
Time frame: Up to 12 weeks
Population: Patients who completed the EORTC QLQ-CIPN20 at pre-treatment-initiation and at least once post-treatment initiation.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Arm I (Cryotherapy) | Area Under the Curve (AUC) EORTC CIPN20 Shooting/Burning Pain in Toes or Feet Item Adjusting for Baseline | 0.0 Average(subscale value*assessment) |
| Arm II (Control) | Area Under the Curve (AUC) EORTC CIPN20 Shooting/Burning Pain in Toes or Feet Item Adjusting for Baseline | 0.0 Average(subscale value*assessment) |
p-value: 0.62Wilcoxon (Mann-Whitney)
Primary
Area Under the Curve (AUC) EORTC CIPN20 Tingling Fingers or Hands Item Adjusting for Baseline
Average Area Under the Curve per assessment (aAUCpa) of EORTC Chemotherapy-Induced Peripheral Neuropathy Module (EORTC QLQ-CIPN20) Tingling Fingers or Hands over 12 weeks adjusting for baseline (item 1; During the past week, did you have tingling fingers or hands?; 1=Not at all, 2=A little, 3=Quite a bit; and 4=Very much). The reported score was transform into 0-100 scale, with higher scores represent fewer symptoms (better QOL). The aAUCpa for the individual item is calculated as the average of each AUC between each sequential assessment from pre-treatment-initiation to the week-12 assessment then subtract the corresponding baseline score, with positive scores represent symptoms has improved from baseline and negative scores represent symptoms has worsen from baseline.
Time frame: Up to 12 weeks
Population: Patients who completed the EORTC QLQ-CIPN20 at pre-treatment-initiation and at least once post-treatment initiation.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Arm I (Cryotherapy) | Area Under the Curve (AUC) EORTC CIPN20 Tingling Fingers or Hands Item Adjusting for Baseline | 0.0 Average(subscale value*assessment) |
| Arm II (Control) | Area Under the Curve (AUC) EORTC CIPN20 Tingling Fingers or Hands Item Adjusting for Baseline | -2.1 Average(subscale value*assessment) |
p-value: 0.72Wilcoxon (Mann-Whitney)
Primary
Area Under the Curve (AUC) EORTC CIPN20 Tingling Toes or Feet Item Adjusting for Baseline
Average Area Under the Curve per assessment (aAUCpa) of EORTC Chemotherapy-Induced Peripheral Neuropathy Module (EORTC QLQ-CIPN20) Tingling Toes or Feet over 12 weeks adjusting for baseline (item 1; During the past week, did you have tingling toes or feet?; 1=Not at all, 2=A little, 3=Quite a bit; and 4=Very much). The reported score was transform into 0-100 scale, with higher scores represent fewer symptoms (better QOL). The aAUCpa for the individual item is calculated as the average of each AUC between each sequential assessment from pre-treatment-initiation to the week-12 assessment then subtract the corresponding baseline score, with positive scores represent symptoms has improved from baseline and negative scores represent symptoms has worsen from baseline.
Time frame: Up to 12 weeks
Population: Patients who completed the EORTC QLQ-CIPN20 at pre-treatment-initiation and at least once post-treatment initiation.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Arm I (Cryotherapy) | Area Under the Curve (AUC) EORTC CIPN20 Tingling Toes or Feet Item Adjusting for Baseline | -1.7 Average(subscale value*assessment) |
| Arm II (Control) | Area Under the Curve (AUC) EORTC CIPN20 Tingling Toes or Feet Item Adjusting for Baseline | -4.9 Average(subscale value*assessment) |
p-value: 0.39Wilcoxon (Mann-Whitney)
Secondary
Area Under the Curve (AUC) Per Assessment (aAUCpa) of Worst Pain (Item 1 on the Daily Post-Paclitaxel Questionnaire)
Average Area Under the Curve (AUC) per assessment (aAUCpa) of worst pain (item 1 on the Daily Post-Paclitaxel Questionnaire; Please rate any aches/pain that are new since your last dose of paclitaxel, and that you think might be related to your chemotherapy treatment, by circling ONE number that best describes your aches/pain at its WORST in the last 24 hours.) over 1 week. Scores are reported on a 0-100 scale, where 100=better outcome quality of life (QOL). The aAUCpa is the average of each AUC between each sequential assessment from day 2 through 7 following paclitaxel.
Time frame: 1 week
Population: Patients who completed the Daily Post-Paclitaxel Questionnaire over the first week of paclitaxel were included in this analysis.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Arm I (Cryotherapy) | Area Under the Curve (AUC) Per Assessment (aAUCpa) of Worst Pain (Item 1 on the Daily Post-Paclitaxel Questionnaire) | 95.0 Average(subscale value*assessment) |
| Arm II (Control) | Area Under the Curve (AUC) Per Assessment (aAUCpa) of Worst Pain (Item 1 on the Daily Post-Paclitaxel Questionnaire) | 96.0 Average(subscale value*assessment) |
p-value: 0.67Wilcoxon (Mann-Whitney)