Tea catechins may bind to certain drugs to affect their absorption and bioactivities. Tea catechins may inhibit the activities of drug-metabolizing enzymes and drug transporters or affect the expression of these proteins, either upregulation or downregulation. Although these effects have been demonstrated in studies in vitro and in animal models, such effects have only been observed in limited cases in humans at common doses of human tea consumption. The ingestion of tea catechins from dietary supplements, which could be in large bullet doses, may produce more profound effects on drug metabolism, and such effects with drugs need to be further investigated.
Background The advent of anti-PD1 therapy for cancer treatment has led to improvements in response rates and overall survival. However, anti-PD1 therapy has the potential to cause immune-related adverse events (irAEs), which can be treated with corticosteroids if severe. The clinical implications of concomitant immunotherapy and systemic steroids remain unclear, as short courses of steroids do not significantly suppress T-cell function. The primary objective of this study is to determine if the use of concomitant steroids impacts the efficacy of anti-PD1 therapy. Methods This retrospective, single-center study reviewed adult patients who received at least four cycles of nivolumab or pembrolizumab for the treatment of melanoma, non-small cell lung cancer (NSCLC), or renal cell carcinoma from November 2014 to February 2016. Patients who received steroids (prednisone equivalent >10 mg) during anti-PD1 therapy were divided into two main cohorts based on the duration of steroid administration of ≤2 weeks or >2 weeks. Time to disease progression, overall response, and overall survival were assessed. Results Twenty-seven of 55 patients (13 melanoma, 11 NSCLC, 3 renal cell carcinoma) required steroids during anti-PD1 therapy. In patients who received steroids, median time to disease progression was 5.6 months for melanoma, 5.8 for NSCLC, and 2.0 for renal cell carcinoma. The overall response rate (ORR) was 3/13 (23%) for melanoma, 6/11 (54%) for NSCLC, and 1/3 (33%) for renal cell carcinoma. Median overall survival was 11.9 months for melanoma, 9.9 for NSCLC, and not reached for renal cell carcinoma. Thirteen patients who had received steroids expired; 11 of these patients had received prednisone >10 mg/day for >2 weeks. Conclusion High-dose steroids for long durations during anti-PD1 therapy may be associated with poorer survival outcomes.
Introduction Renal cell carcinoma (RCC) is a highly vascularized and immunogenic tumor. At the time of this study, there was limited published data on the combination of tyrosine kinase inhibitors and immune checkpoint inhibitors in patients who were heavily pretreated. At our institution, providers have used these combinations in heavily pretreated patients. Methods We conducted a retrospective review of patients receiving this combination with the primary objectives of assessing duration of therapy and toxicities and a secondary objective of disease progression at six months. We included adult patients with confirmed mRCC receiving combination therapy (immune checkpoint inhibitors/tyrosine kinase inhibitors) any time after January 2015. Electronic medical records were reviewed for pertinent data and follow-up descriptive statistics were performed. Results Fifteen patients were on combination immune checkpoint inhibitors/tyrosine kinase inhibitors, with a median of three lines of previous therapy. The median duration of combination therapy was 7.2 months (range: 0.2 to 39.8) with 126 incidences of toxicities. The most frequent toxicity was fatigue (n = 15), followed by diarrhea (n = 8), anorexia (n = 7) and palmar-plantar erythrodysesthesia (n = 7). Overall, 9 (60%) patients experienced at least one grade 3 or 4 toxicity. Eight of 15 (53%) patients remained on therapy at the six-month mark and did not have progression confirmed by an oncologist. Of the 15 patients, 10 discontinued therapy due to progression, 2 due to intolerable side effects, 2 transitioned to end of life care, and 1 patient was still ongoing at the time of data collection. Conclusion Based on this review, it appears that combination tyrosine kinase inhibitors/immune checkpoint inhibitors therapy in pre-treated patients with mRCC is tolerable and beneficial.
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