Supplementary Material for: Interference of Herbal Medicine with Axitinib in Metastatic Renal Cell Cancer Treatment: a Case Study

Introduction: The awareness and the clinical relevance of the potential interactions between standard and complementary medicine are increasing in medical oncology. Nonetheless, the research and experience of the efficacy, safety and toxicity of herbal substances is poorly documented. Case presentation: Here we report the case of a 68-year-old female patient who had been diagnosed with advanced renal cell cancer (mRCC) with metastasis in the liver and pancreas and had undergone surgical resection with hemi-hepatectomy and resection of metastasis in the pancreas in November 2021. Thereafter, chemotherapy was immediately initiated with three-weekly infusions of pembrolizumab and daily intake of the tyrosine kinase inhibitor (TKI) axitinib. Surprisingly, three months after initiation of systemic treatment, the patient developed early progression and metastasis in the liver, which was then treated with selective internal radiotherapy (SIRT). Despite continued axitinib and pembrolizumab treatment, a short-term follow-up in November 2022 revealed another metastatic lesion in her pancreas. Due to the presumed lack of response to treatment, the plasma concentration of axitinib was measured and found to demonstrate sub-therapeutic levels of exposure. Upon extended anamnesis, the patient reported regular intake of herbal substances prescribed by her oncology acupuncturist for gastrointestinal complaints associated with the primary operation. Conclusion: Further clinical-pharmacological workup strikingly demonstrated a reduction of the therapeutic concentration of axitinib of about 90%, likely caused by herbal drugs such as Dang gui and Bai zhu.