The prospective multicenter study of relation between 5-HIAA/substance P plasma concentration transition and nausea/vomiting in patients with gastrointestinal cancer receiving moderately emetogenic chemotherapy
Authors: T. Muranaka, Y. Komatsu, S. Ohnishi, M. Yagisawa, K. Sawada, Y. Kawamoto, H. Nakatsumi, S. Yuki, M. Dazai, T. Saiki, A. Ishiguro, M. Tateyama, K. Ono, N. Sakamoto
Journal: Annals of Oncology (2018)

Introduction: Chemotherapy-induced nausea and vomiting (CINV) is one of the serious adverse events after anti-cancer chemotherapy. We usually administrate 5-HT3 receptor antagonist to prevent from acute CINV, and an aprepitant, which is a NK1 receptor antagonist to block substance P, to prevent from delayed CINV. There are some reports that plasma substance P concentration raised up after administration of high dose cisplatin which is categorized as high emetogenic chemotherapy (HEC), but there are few reports to check their transition in patients after receiving oxaliplatin or irinotecan which is categorized as moderately emetogenic chemotherapy (MEC). Methods: This is a multicenter exploratory observational research in Japanese patients receiving chemotherapy for gastrointestinal cancer registered as UMIN000021072. The key eligibility criteria are as follows: 1) Diagnosed gastrointestinal cancer; 2) Planned to receive high dose cisplatin (for up to five patients in cohort 1, for validation of measurement), oxaliplatin or irinotecan; 3) 20 years of age or older; 4) ECOG PS of 0, 1 or 2; 5) Keeping adequate major organ function. By sampling the patients' blood before and 4, 24, 48, 72 and 96 hours after HEC/MEC administration, we measured the changes in plasma concentration of substance P/5-HIAA after chemotherapy, and survey the relevance of plasma concentrations of substance P/5-HIAA and CINV measured by visual analogue scale (VAS). We defined over 25 millimeter in 100 millimeter by patients-oriented VAS as positive nausea, and recorded the number of vomiting. Plasma 5-HIAA concentration was measured by SRL Inc. and plasma substance P concentration was measured by Kyowa Medex Co., Ltd. Results: We could measure plasma concentration of both plasma 5-HIAA and Substance P concentration in all 3 consecutive HEC cases, and 36 patients were enrolled who received MEC for gastric cancer or colorectal cancer. 5 patients were excluded (one was violated exclusion criteria, 4 did not write VAS), and 31 patients were fully analyzed. Delayed CINV was occurred in 15 of 31 patients. The change ratio (%) of plasma concentration of 5-HIAA in 4, 24, 48, 72 and 96 hours after MEC administration compared with the baseline in patients "without" vs "with" delayed CINV were 131.04 vs 63.33 (p = 0.0086), -2.17 vs 7.14 (p = 0.46), -10.17 vs 9.30 (p = 0.12), 5.17 vs 0.00 (p = 1.00), 5.26 vs 2.29 (p = 0.56), respectively. Those of substance P were 9.46 vs 21.83 (p = 0.61), -0.01 vs -0.30 (p = 0.97), -2.74 vs -2.83 (p = 0.99), 2.83 vs 2.78 (p = 1.00), 4.59 vs -1.30 (p = 0.59), respectively. Conclusion: Small ratio between 5-HIAA 4 hours after MEC administration and before might be an early predictive marker of delayed CINV. Plasma concentration of SP may not reflect CINV due to substance P.