Use of Metronidazole Gel to Control Malodor in Advanced and Recurrent Breast Cancer

Abstract

Intolerable malodor emanating from ulcerated tumors as a result of anaerobic infection is a serious problem in the management of advanced and recurrent breast cancer. Metronidazole can control this malodor, but its oral use may cause adverse reactions. We therefore formulated a metronidazole gel, since no equivalent preparation is commercially available in Japan, and used it in five female patients (four with advanced cancer and one with recurrent cancer) admitted to our hospital between March 1994 and July 1995. The patients were aged between 47 and 71 (median: 59) years, and the duration of morbidity in the four patients with advanced cancer ranged from 10 months to four years. In three patients, the tumors were larger than 10 cm x 10 cm. Metronidazole gel was applied to the surface of ulcerated tumors once or twice daily. Independent assessments by the patient, doctor and nurse were unanimous, and revealed that the malodor was alleviated in one patient after three days, and removed in four patients after two to five (median: four) days of metronidazole gel treatment. Culture of swabs showed a decrease or disappearance of anaerobic colonies. Adverse reactions characteristic of metronidazole did not occur. The topical use of metronidazole in a gel form will improve the quality of life for patients with malodorous ulcerated tumors and facilitate intensive treatment of the underlying disease.

Investigation of the Safety of Topical Metronidazole from a Pharmacokinetic Perspective

“…Assuming a similar extent of absorption as observed in this study, plasma MTZ concentration after application of 70 g (reported as the average daily dose) of MTZ ointment was calculated as 74 µg/mL, which is about 4 times higher than the maximum plasma concentration (about 20 µg/ mL) occurring with repeated oral administration of 1 MTZ tablet (250 mg) twice daily for 7 d. 31) Furthermore, MTZ ointment was used continuously for only 56 d on the patient presented in this study because the skin ulcer site showed improvement from the antitumor effects of chemotherapy. However, when used for the purpose of eliminating or mitigating cancerous malodor occurring with the invasion and metastasis of malignant tumors to the skin, MTZ ointment is used for a longer period of time, and the amount used tends to increase over time, 3,7) which could result in even higher concentration of MTZ in plasma.…”

“…[1][2][3] Malodor causes discomfort to the patient, of course, but also to people in the vicinity of the patient, such as family members and healthcare workers, and can make it difficult to maintain human relationships, damage the self-esteem of the patient, and cause a decrease in quality of life. Volatile sulfides and volatile fatty acids produced by anaerobic bacteria (such as Bacteroides fragilis) that have infected sites of ulceration are suggested to contribute to malodor.…”

“…Volatile sulfides and volatile fatty acids produced by anaerobic bacteria (such as Bacteroides fragilis) that have infected sites of ulceration are suggested to contribute to malodor. [2][3][4][5] The application of topical metronidazole (MTZ) preparations has been reported to be effective against cancerous malodor, 2,3,6) but because topical MTZ preparations are not sold in Japan, many hospitals prepare these agents in-house. A survey of the literature conducted by the Japanese Society of Hospital Pharmacists 7) in 2010 reported that topical MTZ preparations were prepared at standards between 0.75% and 1%, with an average one-time dose of 70 g. The plasma MTZ concentration of 32 ng/mL has been reported when 1 g of 1% MTZ gel was applied to the face once daily for 7 d. 8) Cancerous tissue with ulcer-like symptoms is likely to have a higher capacity to absorb drugs than normal skin, due to the fact that the protective mechanisms have been compromised.…”

Improving malodour management in advanced cancer: a 10-year retrospective study of topical, oral and maintenance metronidazole

“…Anaerobic cultures from fungating wounds have grown Bacteroides, Fusobacterium, Peptostreptococci and Veillonella. 5…”

“…They described a range of smells caused by various organic acids: a sour odour (acetic acid), a cheese odour (isobutyric acid), ‘cheese and vomit’ odour (butyric acid) and ‘cheese and foot’ odour (isovaleric acid) 6. These organic fatty acids, the products of lipid catabolism, were earlier thought to be the main chemicals causing malodour 5 7. None of these descriptions, however, quite capture the nauseating smell of a putrid tumour 2.…”