Case Report: Prolonged Anorexia With Nausea Caused by Immune Checkpoint Inhibitors for Malignant Melanoma Treated Using Kampo Medicines Bukuryoingohangekobokuto and Ninjin’yoeito

Abstract

Immune checkpoint inhibitors (ICIs) are indicated for several cancers, including malignant melanoma. Anorexia and nausea resulting in malnutrition are side effects of ICIs. In such cases, conventional drugs are used for symptom relief, but the symptoms may persist. We report a case of advanced malignant melanoma with prolonged anorexia and nausea, which occurred after nivolumab administration, and was successfully treated using Kampo medicines. A 75-year-old man with nasal bleeding visited our hospital. A nasal scope revealed an obstructive tumor in the left nasal concha. Tissue biopsy showed malignant melanoma, and computed tomography showed metastasis to the liver and bone. Thus, the patient was diagnosed with stage IV malignant melanoma. He received radiotherapy (30 Gy) and nivolumab with ipilimumab four times, followed by nivolumab administration alone. During the administration of nivolumab, he complained of severe anorexia and nausea, with a numeric rating scale (no symptoms, 0; severe symptoms, 10) score of 10. He could not consume food because of these symptoms, even after nivolumab administration was discontinued. His blood pressure was 92/59 mmHg, his performance status (PS; no fatigue, 0; bedridden or disabled, 4) was 4, and his body weight gradually decreased from 60 to 39 kg in a month. The patient showed malnutrition and dehydration and experienced anxiety and depression. Nivolumab was terminated, and conventional symptomatic drugs were prescribed, but the symptoms persisted. We then prescribed 9.0 g/day of ninjin’yoeito (TJ-108, Tsumura and Co.) to allow recovery from anorexia and subsequently added bukuryoingohangekobokuto (TJ-116, Tsumura and Co.) to treat the persistent nausea. After treatment with these two Kampo medicines, the patient’s appetite gradually recovered. Along with the recovery of nutritional status, his PS improved to 0, his anxiety and depressive state improved, and his body weight increased to 60 kg. The patient remained in good condition without cancer recurrence. The patient’s clinical course shows the usefulness of Kampo medicine as supportive care for symptom relief and maintenance of nutritional and mental status during cancer treatment.

Review of frequently used Kampo prescriptions: Part 4, Ninjin'yoeito

“…Table 4 presents the list of clinical studies and Table 5 presents the list of case reports of NYT according to the search strategy. Five randomized clinical trials (RCT) [59][60][61][62][63], four observational studies [64][65][66][67], and 12 case reports were searched [68][69][70][71][72][73][74][75][76][77][78][79][80]. Herein, we summarize the findings of clinical studies on NYT.…”

“…Takayama et al reported cases of anorexia during the treatment of malignant melanoma and esophageal cancer. In both cases, anorexia improved after the administration of NYT [63, 64]. Aomatsu et al reported the supportive role of NYT on postoperative weakness or during anticancer treatment in colon cancer [65, 66].…”

“…Takayama et al reported cases of anorexia during the treatment of malignant melanoma and esophageal cancer. In both cases, anorexia improved after the administration of NYT [63,64]. Aomatsu 2005 [61] Abbreviation: AD, Alzheimer's disease; COPD, chronic obstructive pulmonary disease; Hb, hemoglobin; NYT, ninjin'yoeito; RCT, randomized controlled trial.…”

Psychiatric disorders associated with immune checkpoint inhibitors: a pharmacovigilance analysis of the FDA Adverse Event Reporting System (FAERS) database

“…reported a case of malnutrition due to severe anorexia and nausea during treatment with nivolumab. 35 Delirium or acute confusional state is a clinical syndrome characterized by impairment of consciousness, cognitive function or perception, with serious adverse consequences such as death and dementia. 36 The occurrence of both is usually associated with systemic disease, brain disease or drug toxicity, often induced by hypokalaemia and hyponatremia, 37 while the latter is associated with ICIs.…”