Calendula Ointment Reduces Radiation-Induced Dermatitis in Breast Cancer Patients
Donald. Brown, ND, is the founder and director of Natural Product Research Consultants, Inc. He serves on the Advisory Board of the American Botanical Council and the President’s Advisory Board of Bastyr University, Seattle. Dr. Brown has served as an advisor to the Office of Dietary Supplements at the National Institutes of Health.
Source: Pommier P, et al. Phase III randomized trial of Calendula officinalis compared with trolamine for prevention of acute dermatitis during irradiation for breast cancer. J Clin Oncol 2004;22:1447-1453.
Abstract: In a randomized, single-blind clinical trial, 254 women (ages 18-75 years; mean age 55.8 years) with breast cancer receiving postoperative radiation therapy were randomized to receive either topical calendula (Calendula officinalis L. [Asteraceae]; Pommade au Calendula par Digestion*; Boiron Ltd., Levallois-Perret, France) ointment in 100 g tubes or trolamine (Beirsdrof, Inc., Wilton, CT). Women applied the study medication at least twice per day, but could apply more if their dermatitis and pain warranted additional applications. Participants applied topical treatment at the onset of radiation therapy and until its completion. For inclusion in the trial, women were required to have nonmetastatic adenocarcinoma treated with either lumpectomy or mastectomy with and without adjuvant postoperative chemotherapy or hormonal therapy, and referred to the Department of Radiotherapy (Centre Léon Bérard, Lyon, France) for postoperative radiation therapy. The clinical trial lasted eight months.
The primary outcome measure was the efficacy of calendula and trolamine for the prevention of grade 2 or higher dermatitis caused by radiotherapy for breast cancer. Skin toxicity grading previously has been defined by the Radiation Therapy Oncology Group. Grade 0 corresponds to no physical signs of skin toxicity. Grade 1 skin toxicity displays follicular, faint, or dull erythema (redness of the skin caused by dilation and congestion of the capillaries); epilation (the act or result of removing hair); dry desquamation (the shedding or peeling of the epidermis in scales); or decrease in sweating. Grade 2 skin toxicity is tender with bright erythema; patchy, moist desquamation; or moderate erythema. Grade 3 skin toxicity is defined as having confluent, moist desquamation in areas other than skin folds, and pitting edema. Grade 4 skin toxicity exhibits ulceration, hemorrhage, and necrosis. Secondary measures included weekly assessments of pain using a visual analog scale (VAS), interruptions to treatment due to skin reactions from the ointments, patient satisfaction, and the quality of the study medication.
Grade 2 or 3 skin toxicity was experienced in 41% of the women in the calendula treatment group compared to 63% of women in the trolamine group (P < 0.001). Significantly fewer women in the calendula group also experienced grade 3 toxicity (7% using calendula vs. 20% using trolamine; P = 0.034). Grade 2 or 3 skin toxicity was observed in fewer women using calendula compared to women using trolamine in the submammary fold (34% vs. 50%, respectively; P = 0.02), armpit and tangential area (28% vs. 48%, respectively; P = 0.004), and the supraclavicular nodes (28% vs. 63%, respectively; P < 0.001). None of the women in either group experienced grade 4 toxicity. The VAS for pain was significantly less in the calendula group compared to the trolamine group (1.54 vs. 2.10, respectively; P = 0.03).
Volunteers using the calendula ointment did not experience any allergic reactions; four patients using trolamine experienced pruritis and hives. Twelve treatment interruptions (9%), for a mean duration of 10 days each, occurred in the trolamine group due to skin toxicity. No interruptions for skin toxicity occurred in the calendula group. Thirty percent of volunteers rated application of the calendula ointment as "difficult" compared to 5% of volunteers using trolamine. Two patients discontinued using the calendula ointment because of this difficulty. Eighty-four percent of physicians rated adherence to application of the medications as "good" for calendula compared to 92% for adherence to trolamine (P = 0.047). Women in the calendula group used 1.62 times less ointment during the study period compared to women using trolamine (2.7 tubes vs. 4.4 tubes, respectively).
Comments by Donald Brown, ND
Completed at the department of radiation oncology at the Centre Léon Bérard in Lyon, France, and funded by a research grant from Boiron, Ltd., France, the results of this clinical trial suggest that calendula ointment is a safe and cost-effective treatment for prevention of mild-to-severe radiation-induced dermatitis in women being treated with radiation therapy for breast cancer. Although the trial lacks a placebo group (based on ethical concerns), the comparison to the control substance, trolamine, points to calendula as a possible alternative for women wishing to avoid using steroid-based creams or other more aggressive treatments such as sucralfate or hyaluronic acid.
A soap substitute used for burn patients, trolamine is widely recommended in France for radiation-induced dermatitis because it has a small risk of side effects. In fact, the researchers note that it has been used for several years in their clinic. This trial suggests not only that calendula is superior for preventing acute dermatitis but also that it is less likely to lead to side effects such as pruritis or hives. However, it is important to note that one study has found that trolamine was no more effective in preventing radiation-induced dermatitis than supportive care or no treatment at all,1 while another study found that trolamine might have curative properties.2 It also should be noted that other nonsteroidal topical agents (e.g., aloe vera, soy oil) have failed to prevent dermatitis in smaller clinical trials.1,3
In a randomized, open-label, parallel group study with 156 patients suffering from second- and third-degree burns, the effectiveness of topical calendula ointment was compared with Elase (a "proteolytic" ointment; Pfizer, New York, NY) and petroleum jelly.4 The calendula ointment was found to be better tolerated but only marginally better than petroleum jelly alone for healing. Randomized trials with more aggressive treatments, such as corticosteroid creams and sucralfate, have accrued few patients and the radiation sites were more numerous and not as uniform as those in the reviewed study with calendula.5,6 The results using calendula certainly point to a follow-up trial using corticosteroid cream or ointment as a comparison to calendula ointment.
Traditionally, calendula (pot marigold) has been used both externally for treating superficial wounds and burns and internally for stomach ulcers and liver complaints.7 The German Commission E approves the topical use of flower preparations for the treatment of poorly healing wounds.8 Although the wound healing and anti-inflammatory actions have been demonstrated, the active principles that promote wound healing have yet to be identified clearly.9 Some phytomedicine experts warn that the potent stimulation of granulation tissue by calendula may result in later risk of keloid formation when used for more severe wounds.10 Warnings for the topical use of the herb also extend to allergic reactions, particularly in those individuals with known hypersensitivity to plants of the Asteraceae family, which also includes echinacea, chamomile, and milk thistle.11
Conclusion
The results of this trial suggest that calendula ointment may be an effective option in the prevention of acute dermatitis in women receiving radiation therapy for breast cancer. Although topical treatments such as corticosteroid cream often are used for the treatment of acute radiation-induced dermatitis, there are no standard treatments for prevention of the condition—one that affects approximately 80% of women receiving radiation therapy. Hopefully, manufacturers of calendula ointments will take a close look at the issue of application difficulties and work on topical forms that are easier to apply.
*The calendula product used in the study is obtained by incubation of calendula (marigold) at 75° C in petroleum jelly to extract the liposoluble parts of the plant.
References
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2. Fisher J, et al. Randomized Phase III study comparing best supportive care to biafine as a prophylactic agent for radiation-induced skin toxicity for women undergoing breast irradiation: Radiation Therapy Oncology Group (RTOG) 97-13. Int J Radiat Oncol Biol Phys 2000;48:1307-1310.
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5. Bostrom A, et al. Potent corticosteroid cream (mometasone furoate) significantly reduces acute radiation dermatitis: Results from a double-blind, randomized study. Radiother Oncol 2001;59:257-265.
6. Maiche A, et al. Skin protection by sucralfate cream during electron beam therapy. Acta Oncol 1994;33: 201-203.
7. Ellingwood F. American Materia Medica, Therapeutics and Pharmacognosy. Portland, OR: Eclectic Medical Publications; 1983.
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9. Schulz V, et al. Rational Phytotherapy: A Physicians’ Guide to Herbal Medicine. Berlin: Springer-Verlag; 2001:310.
10. Weiss RF, Fintelmann V. Herbal Medicine. Stuttgart, Germany: Thieme; 2000:312.
11. Barnes J, et al. Herbal Medicines: A Guide for Healthcare Professionals. London: Pharmaceutical Press; 2002:103-106.
Brown D. Calendula ointment reduces radiation-induced dermatitis in breast cancer patients. Altern Ther Women's Health 2005;7(5):37-38.
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