Aprepitant

All animal experiments in this study were approved by the Animal Care and Use Committee of Henan Provincial Orthopedic Institute, and we followed the protocols of the National Institutes of Health Guide for the Care and Use of Laboratory Animals (NIH Publications No. 8023, revised 1978). Based on a previous study [11 (link)], male rats weighing 250–300 g were anesthetized with 2.5% pentobarbital sodium, and then, the IVD of L4-5 was exposed using a transabdominal median approach. Subsequently, the IVD was penetrated vertically to reach the NP using an 18-gauge needle at a depth of 2 mm, and then, drugs were administered with a microsyringe. After that, the incision was sutured layer by layer with silk thread, and the animals were kept warm until they regained consciousness. For the behavioral study, seven groups were established: the sham-surgery group, puncture + saline group, puncture + NAC (N-acetyl-L-cysteine) group, puncture + H₂O₂ group, puncture + SP 0.1 μg group, puncture + SP 1 μg group, and puncture + aprepitant (an antagonist of the neurokinin 1 receptor, which blocks the effect of SP) group. To avoid bias, analgesic drugs and antibiotics were not used before or after the surgery. H₂O₂ was diluted in deionized water and administered at a concentration of 100 μM per disc after puncture. NAC (CAS No. 616-91-1, MedChemExpress, NJ, US) was administered at a concentration of 1 mM per disc after puncture. Substance P (cat No. 1156/5, R&D Inc., MN, US) was administered at a concentration of 0.1 μg or 1 μg per disc, and aprepitant (CAS No. 170729-80-3, MedChemExpress, NJ, US) was administered at a concentration of 1 mM per disc. For immunohistochemistry (IHC) and Western blot analysis about H₂O₂-indcued SP, the H₂O₂ was inoculated into rodent IVD with a 24-gauge needle, and the tissue was harvested 24 hours later.

DCF therapy consisted of intravenous infusion of DOC (70 mg/m²) for 1 h, followed by intravenous infusion of CDDP (70 mg/m²; dosage was adjusted according to Ccr) for 2 h on day 1, and continuous intravenous infusion of 5-FU (700 mg/m²) from days 1 to 5. In this study, one cycle of 21 days or 28 days was adopted for the purpose of neoadjuvant chemotherapy (NAC) or other purposes (e.g., treatment for unresectable/recurrent esophageal cancer, hereafter referred to as “non-NAC”), respectively. Oral levofloxacin (500 mg; dosage adjusted according to Ccr) was administered to all patients from days 5 to 15 as prophylaxis for FN. MgSO₄ (20 mEq) was administered before CDDP administration, and adequate hydration with normal saline was administered [32 (link)], to avoid CDDP-induced renal dysfunction. In our institute, PEG-G is administered on day 7 of DCF therapy because the G-CSF guideline [33 (link)] recommends administering it 24 h after anticancer drug administration.
The antiemetic agents used were neurokinin 1 (NK₁) receptor antagonist ((fos)aprepitant), serotonin (5-hydroxytryptamine)-3 (5-HT₃) receptor antagonist (palonosetron), and dexamethasone [34 (link)]. The patients received oral aprepitant (125 mg) or intravenous fosaprepitant (150 mg) on day 1. Intravenous palonosetron (0.75 mg) and dexamethasone (9.9 mg) were administered on day 1, followed by intravenous dexamethasone (6.6 mg) on days 2–5. The patients also received oral aprepitant (80 mg) on days 2 and 3 when they received oral aprepitant on day 1.

During stem cell mobilization all patients received meloxicam to enhance stem cell mobilization and ondansetron as prophylactic antiemetic therapy. Sulfamethoxazole-trimethoprim was given as prophylaxis for pneumocystis jiroveci infection from the start of HDCT until 3 weeks after ASCT. Fluconazol was administered from HDCT until the end of aplasia to prevent fungal infections, and valaciclovir as virostatic prophylaxis from day +1 until 3 months post-ASCT. Dexamethasone was given from day −4 to ASCT and from day +9 to +13 after ASCT as prophylaxis of engraftment syndrome. Antiallergic prophylaxis before ASCT was performed with iv methylprednisolone and clemastine. Allopurinol was given to prevent tumor lysis syndrome during HDCT. Additionally, after ASCT all patients received folic acid for 8 weeks to improve hematopoietic recovery. Zoledronic acid was given at day +1 after ASCT. All patients received G-CSF (filgrastim) 5 μg/kg/day from day +6 to +12 after ASCT. Further supportive medication included aprepitant, ondansetron, esomeprazole, enoxaparin natrium and furosemide.