Breast Cancer
Conditions
Keywords
Radiation dermatitis in breast cancer patients
Brief summary
Ionizing radiation is a toxic agent and widely accepted form of treatment for various types of cancer. Despite advances in medical technology, radiation therapy still causes severe early and late skin effects. Radiation-induced dermatitis occurs in approximately 80% of patients. Important consequences of radiation-induced dermatitis include impairment of the quality of a patient's life due to pain and premature interruption of radiation treatment, which in turn, may be impair good local control of disease. The biological pathways responsible for acute radiation-induced dermatitis remain unclear. Currently, there is no standard treatment for the prevention of radiation-induced dermatitis with demonstrated effectiveness. The aim of this randomized, double-blind, placebo-controlled pilot study is to assess the effectiveness of curcumin for the prevention of acute radiation-induced dermatitis during postoperative radiotherapy for breast cancer. We hypothesize that curcumin, a natural phenolic compound found in both turmeric and curry powders, can prevent or alleviate radiation-induced skin reactions in breast cancer patients receiving radiotherapy.
Detailed description
Specifically, this clinical pilot study will develop data necessary to calculate a sample size for a larger study to be conducted through the National Cancer Institute (NCI) Community Clinical Oncology Program (CCOP) mechanism. Specifically, this pilot project will investigate: 1) if curcumin can prevent or alleviate radiation-induced skin reactions in cancer patients receiving radiotherapy and 2) if skin pigmentation, as well as pain and psychophysiological factors, can predict the severity of radiation-induced dermatitis. Potential future research studies may be conducted to identify the biological mechanisms involved in radiation-induced dermatitis and the radioprotective function of curcumin.
Interventions
Patients take 2.0 grams curcumin (four 500mg capsules) three times daily by mouth for prescribed course of radiation treatment (\ 4-7 weeks)
DRUGPlacebo
Patients take 2.0 grams placebo (four 500mg capsules) three times daily by mouth for prescribed course of radiation treatment (\ 4-7 weeks)
Sponsors
University of Rochester
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
FEMALE
Age
21 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Female with a diagnosis of, non-inflammatory breast adenocarcinoma and be referred for post-operative radiotherapy without concurrent chemotherapy. * Participants must be at least 21 years of age. * Participants must not be pregnant. * Participants can be from any racial or ethnic origin. * Breast adenocarcinoma could have been treated by either lumpectomy or mastectomy with or without adjuvant or neoadjuvant chemotherapy or hormonal treatment. * Participants with in situ breast cancer are eligible. * Participants who are prescribed concurrent hormone treatment with radiation treatment are eligible. * Participants must be scheduled to receive five sessions of radiation therapy per week (1 session per day) for at least four weeks using standard (1.8-2.0 Gy per session)or Canadian (2.2-2.5 Gy per session)irradiation fractionation. * A time period of three weeks must elapse after chemotherapy and surgery before beginning the study. * The total dose prescribed to the whole breast should be 50 Gy or greater. * Participants must be able to understand English and able to complete assessment forms (all assessment forms are in English). * Participants must be able to swallow medication. * Topical skin agents, e.g., Aquaphor, Cetaphil, or other emollients, are allowed either PRN or prophylactically. * Participant must give informed consent.
Exclusion criteria
* Patients with bilateral breast cancer are not eligible. * Patients who have had previous radiation therapy to the breast or chest are not eligible. * Patients who are prescribed chemotherapy concurrently with radiation treatment are not eligible. * Patients who will be receiving treatment with Herceptin (trastuzumab), anti-coagulants, or anti-human epidermal growth factor receptor (EGFR) drugs, e.g. Iressa (gefitinib), Erbitux (cetuximab, C225), concurrently with their radiation therapy are not eligible. * Patients cannot have had breast reconstructions, implants, and/or expanders. * Patients with known radiosensitivity syndromes (e.g., Ataxia-telangiectasia) are not eligible. * Patients with collagen vascular disease, vasculitis, unhealed surgical sites, or breast infections are not eligible. * Patients whose baseline blood tests meet the following criteria are not eligible: greater than or equal to Grade 2 change Hemoglobin (i.e., 25% decrease from baseline); greater than or equal to Grade 1 change in Platelets (i.e., less than 75,000/mm3); greater than or equal to Grade 2 change in PT and PTT(i.e., 1.5-2x upper level normal (ULN)); greater than or equal to Grade 1 change in AST, ALT (i.e., greater than 2.5x ULN); greater than or equal to Grade 1 change in Bilirubin (i.e., greater than 1.5x ULN); greater than or equal to Grade 1 change in Creatinine (i.e., greater than 2x ULN).
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Severity of Dermatitis in Radiation Treatment Site in Breast Cancer Patients | 4-7 weeks (prescribed course of radiation) | The severity of radiation dermatitis was measured using the Radiation Dermatitis Severity (RDS)Scale which ranges from 0.0 to 4.0 with increments of 0.5. The RDS scale is a revised form of the NIH Common Toxicity Criteria to account for color and subtle texture changes in the skin. The worst dermatitis (i.e., highest RDS score) at the end of treatment was used for the primary analysis of severity of radiation dermatitis in each treatment group. Additionally, we performed repeated measure analyses to examine the severity of dermatitis over time in each arm. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Moist Desquamation at Radiation Treatment Site | 4-7 weeks (prescribed course of radiation) | The presence of moist desquamation at the end of radiation treatment was examined between curcumin and placebo treatment groups. We compared the number of participants (or percentage) with moist desquamation between each treatment group. |
| Redness at Radiation Treatment Site | 4-7 weeks (prescribed course of radiation) | Redness at radiation treatment site was measured using a CR-400 Colorimeter (Konica Minolta). The colorimeter uses the L\*a\*b\* color scale. We used a\* values (redness) which range from 0.0 to 20.0. The lower the number value, the lower amount of redness. Therefore, high number values represent large amounts of redness. |
| Pain at Radiation Treatment Site | 4-7 weeks (prescribed course of radiation) | The McGill Pain Questionnaire-Short Form (MPQ-SF) was used to determine the participants pain at treatment site. The MPQ-SF contains three subscales: affective pain, sensory pain, and perceived pain. This outcome measure compared the total pain score (range 0 to 50)and subscale scores (sensory subscale range 0 to 33; affective subscale range 0 to 12; perceived pain subscale 0 to 5) at the end of radiation therapy between the two treatment arms. |
Countries
United States
Participant flow
Recruitment details
Enrollment for this trial began January 18, 2008 and ended on January 27, 2010. All patients were recruited and treated at the University of Rochester Cancer Center. Of the 213 breast cancer patients prescribed radiation therapy during this timeframe, 67 patients were approached for particiaption in the trial.
Participants by arm
| Arm | Count |
|---|---|
| Curcumin C3 Complex Patients take 2.0 grams curcumin (four 500mg capsules) three times daily by mouth for prescribed course of radiation treatment (\
4-7 weeks). | 17 |
| Placebo Patients take 2.0 grams placebo (four 500mg capsules) three times daily by mouth for prescribed course of radiation treatment (\
4-7 weeks). | 18 |
| Total | 35 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Ineligible: RTOG study conflict | 1 | 0 |
| Overall Study | Protocol Violation | 1 | 1 |
| Overall Study | Withdrawal by Subject | 1 | 1 |
Baseline characteristics
| Characteristic | Placebo | Curcumin C3 Complex | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 5 Participants | 2 Participants | 7 Participants |
| Age, Categorical Between 18 and 65 years | 13 Participants | 15 Participants | 28 Participants |
| Age Continuous | 53.7 years STANDARD_DEVIATION 7.55 | 50.4 years STANDARD_DEVIATION 9.51 | 51.8 years STANDARD_DEVIATION 8.21 |
| Region of Enrollment United States | 18 participants | 17 participants | 35 participants |
| Sex: Female, Male Female | 18 Participants | 17 Participants | 35 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 | 0 / 14 | 0 / 16 |
| serious Total, serious adverse events | 0 / 14 | 0 / 16 |
Outcome results
Primary
Severity of Dermatitis in Radiation Treatment Site in Breast Cancer Patients
The severity of radiation dermatitis was measured using the Radiation Dermatitis Severity (RDS)Scale which ranges from 0.0 to 4.0 with increments of 0.5. The RDS scale is a revised form of the NIH Common Toxicity Criteria to account for color and subtle texture changes in the skin. The worst dermatitis (i.e., highest RDS score) at the end of treatment was used for the primary analysis of severity of radiation dermatitis in each treatment group. Additionally, we performed repeated measure analyses to examine the severity of dermatitis over time in each arm.
Time frame: 4-7 weeks (prescribed course of radiation)
Population: We used all 30 participants that fully completed the trial in all of our analyses.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Curcumin C3 Complex | Severity of Dermatitis in Radiation Treatment Site in Breast Cancer Patients | 2.6 units on a scale | Standard Deviation 0.994 |
| Placebo | Severity of Dermatitis in Radiation Treatment Site in Breast Cancer Patients | 3.4 units on a scale | Standard Deviation 0.554 |
Comparison: Hypothesis: The mean RDS for curcumin group is significantly different (i.e., lower) than mean RDS of placebo group at end of radiation treatment.p-value: 0.007795% CI: [-1.3693, -0.2289]Standard pooled variances t-test
Secondary
Moist Desquamation at Radiation Treatment Site
The presence of moist desquamation at the end of radiation treatment was examined between curcumin and placebo treatment groups. We compared the number of participants (or percentage) with moist desquamation between each treatment group.
Time frame: 4-7 weeks (prescribed course of radiation)
Population: All 30 participants who completed the trial were used in all analyses.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Curcumin C3 Complex | Moist Desquamation at Radiation Treatment Site | 4 participants |
| Placebo | Moist Desquamation at Radiation Treatment Site | 14 participants |
Comparison: Hypothesis: The presence of moist desquamation significantly differed between the curcumin group and the placebo group.p-value: 0.0022Fisher Exact
Secondary
Pain at Radiation Treatment Site
The McGill Pain Questionnaire-Short Form (MPQ-SF) was used to determine the participants pain at treatment site. The MPQ-SF contains three subscales: affective pain, sensory pain, and perceived pain. This outcome measure compared the total pain score (range 0 to 50)and subscale scores (sensory subscale range 0 to 33; affective subscale range 0 to 12; perceived pain subscale 0 to 5) at the end of radiation therapy between the two treatment arms.
Time frame: 4-7 weeks (prescribed course of radiation)
Population: All 30 participants that fully completed the trial were used in these analyses.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Curcumin C3 Complex | Pain at Radiation Treatment Site | Sensory Pain Subscale | 4.07 units on a scale | Standard Deviation 3.29 |
| Curcumin C3 Complex | Pain at Radiation Treatment Site | Affective Pain Subscale | 0.50 units on a scale | Standard Deviation 0.76 |
| Curcumin C3 Complex | Pain at Radiation Treatment Site | Perceived Pain Intensity | 1.14 units on a scale | Standard Deviation 0.77 |
| Curcumin C3 Complex | Pain at Radiation Treatment Site | MPQ Total Score | 5.71 units on a scale | Standard Deviation 4.27 |
| Placebo | Pain at Radiation Treatment Site | Perceived Pain Intensity | 0.88 units on a scale | Standard Deviation 0.62 |
| Placebo | Pain at Radiation Treatment Site | MPQ Total Score | 3.50 units on a scale | Standard Deviation 3.43 |
| Placebo | Pain at Radiation Treatment Site | Affective Pain Subscale | 0.50 units on a scale | Standard Deviation 0.82 |
| Placebo | Pain at Radiation Treatment Site | Sensory Pain Subscale | 2.25 units on a scale | Standard Deviation 2.32 |
Comparison: Hypothesis: There is a significant difference in mean MPQ pain scores between the curcumin and placebo groups.p-value: 0.21895% CI: [-1.059, 4.428]ANCOVA
Comparison: Hypothesis: There is a significant difference in mean sensory subscale pain scores between curcumin and placebo groups.p-value: 0.15295% CI: [-0.6, 3.6]ANCOVA
Comparison: Hypohesis: There is a signifcant difference in affective subscale pain scores between curcumin and placebo groups.p-value: 0.795% CI: [-0.7, 1.1]ANCOVA
Comparison: Hypothesis: There is a significant difference in mean perceived pain scores between curcumin and placebo groups.p-value: 0.55995% CI: [-0.4, 0.7]ANCOVA
Secondary
Redness at Radiation Treatment Site
Redness at radiation treatment site was measured using a CR-400 Colorimeter (Konica Minolta). The colorimeter uses the L\*a\*b\* color scale. We used a\* values (redness) which range from 0.0 to 20.0. The lower the number value, the lower amount of redness. Therefore, high number values represent large amounts of redness.
Time frame: 4-7 weeks (prescribed course of radiation)
Population: The 30 participants that fullt completed the trial were used in these analyses.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Curcumin C3 Complex | Redness at Radiation Treatment Site | 4.52 units on a scale (0.0 to 20.0) | Standard Deviation 2.81 |
| Placebo | Redness at Radiation Treatment Site | 6.06 units on a scale (0.0 to 20.0) | Standard Deviation 2.82 |
Comparison: Hypothesis: There is a significant difference in mean redness (i.e., mean a\* number value) between the curcumin and placebo groups.p-value: 0.145ANOVA