Pommier, P., Gomez, F., Sunyach, M.P., D’Hombres, A., Carrie, C., & Montbarbon, X. (2004). Phase III randomized trial of calendula officinalis compared with trolamine for the prevention of acute dermatitis during irradiation for breast cancer. Journal of Clinical Oncology, 22(8), 1447–1453.

To assess effectiveness of calendula for prevention of acute radiation-induced dermatitis of grade 2 or higher during radiation therapy compared with trolamine

Patients were randomly allocated to application of trolamine or calendula on irradiated fields after each session. Patients started topical application of ointment at onset of radiation therapy, twice a day or more, depending on occurrence of dermatitis and pain, until completion. Patients were instructed not to use the agent two hours or less before an irradiation session or before treatment evaluation. No other prophylactic creams, lotions, or gels were allowed. Physicians were free to treat established dermatitis grade 2 or higher or allergy as considered appropriate. Clinicians were blinded to the treatment used

• The study sample was comprised of 254 female patients who were randomized to trolamine (n = 128) or calendula (n = 126) treatment.
• Age ranged from 26.5–74.5 years; mean age was 56.5 years in calendula arm and 55.1 years in trolamine arm.
• All patients were post-lumpectomy or post-mastectomy for nonmetastatic breast cancer.
• Patients received treatment with or without adjuvant postoperative chemotherapy or hormonal treatment.
• Standard irradiation fractionation (2 Gy per session, five sessions per week) was used.

The study took place at Centre Leon Berard in Lyon, France.

The study used a randomized, blinded controlled trial design.

• Acute dermal toxicity was evaluated according to the Radiation Therapy Oncology Group scale.
• Pain was assessed weekly on a 10 cm visual analog scale.
• The occurrence, duration, and reasons for interruption of radiation therapy or of allocated cream application were registered, as were allergic reactions and quantity of agents used.
• At the end of the study, patients completed a questionnaire to assess satisfaction with ease of application, pain, and dermatitis relief.
• Qualitative measures were compared using Chi Square or Fisher’s exact test, as appropriate.
• For quantitative measures, the Student’s t test or Wilcoxon-Mann-Whitney tests were used.

The occurrence of acute dermatitis of grade 2 or higher was significantly lower (41% versus 63%; p < .001) with use of calendula versus trolamine. Benefits were most marked at sites at risk of maceration (submammary fold, armpit, and tangential area) and sites with thin skin. Patients receiving calendula had less frequent interruption of radiation therapy. Mean length of treatment interruption was 10 days (range 2–22 days). Fifteen treatment interruptions were observed in trolamine group, 12 due to skin toxicity. No allergic reactions were observed in the calendula group, whereas four patients in the trolamine group developed allergic-type reactions of pruritus and urticaria. Patients receiving calendula had significantly reduced radiation-induced pain. Mean maximal pain evaluated in calendula group was 1.54 and 2.10 in the trolamine group (p = 0.03). Self-assessed satisfaction was greater with calendula. Prevention of erythema was 69% in the calendula arm versus 39% in the trolamine arm. Prevention of pain was 65% with calendula versus 46% with trolamine. Calendula was considered more difficult to apply as noted by 30% of the calendula group versus 5% of trolamine group. The risk of skin toxicity of grade 2 or higher was significantly increased for women whose body mass index was 25 or higher (p < 0.001), who had received chemotherapy before radiation therapy after a lumpectomy (p = 0.01), and who were using trolamine (p < 0.001).

Calendula was shown to be effective in reducing skin toxicity of radiation compared to trolamine.

Because of differences in texture, color, and smell, it was not possible to perform a double-blind randomized study.