Evaluating Aprepitant single-dose plus granisetron and dexamethasone in children receiving highly emetogenic chemotherapy for the prevention of chemotherapy-induced nausea and vomiting: A triple-blinded randomized clinical trial

ABSTRACT Introduction: This study was performed to evaluate the degree of 3-day chemotherapy-induced nausea and vomiting (CINV) in children with cancer who received highly emetogenic chemotherapy (HEC) to ascertain the efficacy of aprepitant single-dose on dayL 1 plus granisetron and dexamethasone (DEX). Methods: This clinical trial study was conducted on 120 patients in the age range of 5 to 18 years old who received chemotherapy. Patients were divided into two groups; Group A received aprepitant at 125 mg/kg on day 1 orally, followed by 80 mg/kg daily on days 2 and 3 and Group B received a single dose of aprepitant 125 mg/kg on day 1 orally and placebo on days 2 and 3. All groups received granisetron 3 mg/m2 on day 1 and DEX on days 1 to 3. The primary and secondary endpoints were to evaluate the proportion of patients with acute, delayed and overall CINV within each group. Results: There were no significant differences between the two groups for vomiting, nausea or the use of rescue therapy. The number of patients without vomiting on day 1 was similar in both groups (96.5% vs. 98.3%, respectively; p = 0.848). Conclusion: According to the results of this study, a single dose of aprepitant 125 mg/kg was as effective as administering three doses of aprepitant on 3 days. Therefore, the use of a single dose of aprepitant in combination with other standard treatment regimens to prevent CINV in children who received HEC was safe and efficacious and can be beneficial.

Aprepitant plus palonosetron for the prevention of postoperative nausea and vomiting after breast cancer surgery: a double blind, randomized trial

OBJECTIVES: To evaluate the addition of a fourth antiemetic intervention in patients at high risk for postoperative nausea and vomiting (PONV). METHODS: High-risk patients (Apfel score 3 or 4) scheduled for unilateral mastectomy were randomly allocated in one of two groups, oral aprepitant (oral aprepitant 80 mg, intravenous dexamethasone 8 mg, and palonosetron 0.075 mg) and oral placebo (oral placebo, intravenous dexamethasone 4 mg, and palonosetron 0.075 mg). Patients and caregivers were blinded to the group assignments. The primary efficacy endpoints included the incidence of nausea and vomiting, and the secondary endpoints included use of rescue antiemetics during a 48-hour postoperative period. ClinicalTrials.gov: NCT02431286. RESULTS: One hundred patients were enrolled in this study and 91 were analyzed, 48 in group A and 43 in group P. No patient presented with nausea or vomiting in the first 2 hours after surgery. From the 2nd to the 6th hour, the incidence of PONV was 8.33% in group A and 9.30% in group P. In the first 24 hours, the incidence of PONV was 27.08% in the group A and 20.93% in group P. From the 24th to the 48th hour, the incidence of PONV was 8.33% in group A and 13.95% in group P. There were no statistically significant differences in PONV between groups. CONCLUSION: The addition of aprepitant as a third antiemetic resulted in no significant reduction in the incidence of PONV in this population. However, the incidence of PONV was reduced in relation to the general population.

Palonosetron for the prevention of chemotherapy induced nausea and vomiting: a comparative study in a tertiary care hospital from India

Background: Despite advances in symptom management, chemotherapy-induced nausea and vomiting (CINV) remains one of the most dreadful consequences of cancer therapy.Methods: The study was carried out at Medical Oncology Department, Vydehi Institute of Medical Sciences and Research Centre, Bangalore. Hundred and forty-four cancer patients of either sex, aged 18-65 years with adequate blood counts requiring moderately emetogenic chemotherapy (MEC) as per Hesketh classification were included. The patients were prospectively divided into two groups before the initial cycle of chemotherapy. Patients in Group A (n=71) received ondansetron, and dexamethasone along with aprepitant capsules, Whereas, Group B (n=73) received palonosetron, and dexamethasone along with placebo capsules, 30 minutes before chemotherapy. Thereafter the patients were administered with the drugs and observed for nausea and vomiting. The efficiency of both regimens was assessed by adopting validated functional living index emesis (FLIE) questionnaire. Analysis of the data was done using the SPSS 21.0 software.Results: The mean age of the patients was 40.5 years and the male to female ratio was 1:2.4. In all the patients, no changes were detected in the ECG readings after MEC. The nausea and vomiting score were comparable in both groups. No significant difference (p>0.05) was noticed between group A and group B in both mm and in FLIE points. No serious adverse events were found relating to antiemetic treatment.Conclusions: Palonosetron in combination with corticosteroids was non inferior to ondansetron in combination with aprepitant and corticosteroids in controlling acute and delayed stages of CINV in patients requiring MEC. Thus, it can be recommended as first-line therapy for patients treated with MEC.

Evaluation of efficacy of palonosetron versus ramosetron in patients receiving emetogenic chemotherapy

Background: Chemotherapy induced nausea and vomiting is the most distressing side effect of cancer chemotherapy. It can seriously impact patient抯 quality of life, influence the adherence to chemotherapy and progression free survival causing a delay or refusal of potentially life-saving therapy. The objective of this study was to compare the efficacy of palonosetron with ramosetron in achieving complete response to the chemotherapy.Methods: This was a prospective randomized open-label study conducted on 130 patients admitted in Medical Oncology ward of a Tertiary Care Hospitals, Bangalore, India. Patients were randomized to receive either palonosetron 0.25 mg or ramosetron 0.3 mg I.V. along with aprepitant and dexamethasone 30 minutes prior to chemotherapy and were followed up for a period of 5 days post chemotherapy. The observations such as number and severity of vomiting and nausea, the outcome was assessed at the end of 5 days. Pearson抯 Chi-square test was used to demonstrate the difference between both the study groups with respect to various categorical data.Results: The complete response rate in delayed phase was more significant in patients who received palonosetron than patients who received ramosetron (72.3% vs 50.8%). Total control was achieved in 38.5% patients with palonosetron as compared to 15.4% patients with ramosetron.Conclusions: Palonosetron is more efficacious than ramosetron in controlling chemotherapy induced nausea and vomiting especially in delayed phase of emesis.

Research progress in neurokinin-1 receptor antagonist aprepitant used for postoperative nausea and vomiting / 中国医师杂志

Postoperative nausea and vomiting ( PONV) is a common complication after anaesthesia, which hinders the rapid recovery of patients. Aprepitant, one of neurokinin-1 (NK-1) receptor antagonists is mainly used to prevent nausea and vomiting by blocking the binding of substance P to NK-1 receptor. It has the advantages of high selectivity, strong affinity and long half-life, and its new antiemetic target pro-vides a new choice for prophylactic treatment of PONV. This article summarize studies on the prophylaxis of aprepitant in treatment of PONV.

Postoperative nausea and vomiting in patients undergoing colorectal surgery within an institutional enhanced recovery after surgery protocol: comparison of two prophylactic antiemetic regimens / 대한마취과학회지

BACKGROUND: Enhanced recovery protocols (ERP) provide optimal perioperative care for surgical patients. Postoperative nausea and vomiting (PONV) is common after colorectal surgery (CRS). We aim to compare the efficacy of aprepitant to a cost-effective alternative, perphenazine, as components of triple antiemetic prophylaxis in ERP patients. METHODS: Patients who underwent ERP CRS at a single institution from July 2015 to July 2017 were evaluated retrospectively. Only subjects who received aprepitant (Group 1) or perphenazine (Group 2) preoperatively for PONV prophylaxis were included. Patient characteristics, simplified Apfel PONV scores, perioperative medications, and PONV incidence were compared between the groups. PONV was defined as the need for rescue antiemetics on postoperative days (POD) 0–5. RESULTS: Five hundred ninety-seven patients underwent CRS of which 498 met the inclusion criteria. Two hundred thirty-one (46.4%) received aprepitant and 267 (53.6%) received perphenazine. The incidence of early PONV (POD 0–1) was comparable between the two groups: 44.2% in Group 1 and 44.6% in Group 2 (P = 0.926). Late PONV (POD 2–5) occurred less often in Group 1 than Group 2, respectively (35.9% vs. 45.7%, P = 0.027). After matching the groups for preoperative, procedural, and anesthesia characteristics (164 pairs), no difference in early or late PONV could be demonstrated between the groups. CONCLUSIONS: The incidence of PONV remains high despite most patients receiving three prophylactic antiemetic medications. Perphenazine can be considered a cost-effective alternative to oral aprepitant for prophylaxis of PONV in patients undergoing CRS within an ERP.

Aprepitant prophylaxis effectively reduces preventing postoperative nausea and vomiting in patients receiving opioid based intravenous patient-controlled analgesia

BACKGROUND: Aprepitant is effective in prevention of chemotherapy-induced nausea and vomiting, when administrated with other antiemetics. We compared the effectiveness of aprepitant to ondansetron for prevention of post-operative nausea and vomiting (PONV) in patients who received a patient-controlled analgesia (PCA) containing opioids. METHODS: 198 patients were randomized into two groups. The treatment group was received an aprepitant, 80 mg, and the control group received a placebo. General anesthesia with inhalational anesthetics–N2O was performed, and PCA was supplied, which contained opioids-NSAIDs-ondansetron. The primary end-point was the incidence of PONV for postoperative 48 hours, and the secondary end-point was the changes in the relationship between PONV incidence and risk factors. RESULTS: PONV incidence in the treatment group was lower than in the control group (18.6% [95% CI: 10.8–26.3], 33.3% [95% CI: 23.6–43.1], respectively, P = 0.021). Relative risk of PONV in the control group was 1.80 (95% CI: 1.08–3.00, P = 0.010). PONV scores peaked at around postoperative 6 hours, then gradually decreased in the control group but not in the treatment group, which showed lower values than the control group (P = 0.001), and no changing patterns were observed (P < 0.001). Risk factors analyzed were sex, surgery type, history of motion sickness or PONV, and smoking habits. Their effects of all risk factors except sex were abolished in the treatment group. CONCLUSIONS: Prophylactic aprepitant with ondansetron was more effective than ondansetron-only regimen in preventing PONV after volatile anesthesia with opioid-containing PCA. Aprepitant abolished the effects of most of risk factors, so it could be efficacious in a high-risk PONV group.

Aprepitant in combination with palonosetron for the prevention of postoperative nausea and vomiting in female patients using intravenous patient-controlled analgesia / 대한마취과학회지

BACKGROUND: The aim of this study was to evaluate aprepitant in combination with palonosetron as compared to palonosetron alone for the prevention of postoperative nausea and vomiting (PONV) in female patients receiving fentanyl- based intravenous patient-controlled analgesia (IV-PCA). METHODS: In this randomized single-blinded study, 100 female patients scheduled for elective surgery under general anesthesia were randomized to two groups: Group AP (80 mg aprepitant plus 0.075 mg palonosetron, n = 50) and Group P (0.075 mg palonosetron, n = 50). The patients in group AP received 80 mg aprepitant per oral 1–3 h before surgery, while all patients received 0.075 mg palonosetron after induction of standardized anesthesia. All patients had postoperative access to fentanyl-based IV-PCA. The incidence of nausea and vomiting, use of rescue medication, and severity of nausea were evaluated at 6 and 24 h after surgery. RESULTS: The incidence of nausea (54%) and vomiting (2%) in group AP did not differ significantly from that in group P (48% and 14%, respectively) during the first 24 h after surgery (P > 0.05). Patient requirements for rescue medication in group AP (29%) were similar to those in group P (32%) at 24 h after surgery (P > 0.05). There was no difference between the groups in severity of nausea during the first 24 h after surgery (P > 0.05). CONCLUSIONS: Aprepitant combined with palonosetron did not reduce the incidence of PONV as compared to palonosetron alone within 24 h of surgery in women receiving fentanyl-based IV-PCA.

Formula Optimization of Aprepitant Nanocapsules by Central Composite Design-response Surface Method-ology / 中国药师

Objective:To optimize the formula of aprepitant nanocapsules. Methods: The central composite design–response surface methodology was used. The amounts of hydroxg propyl cellulose(HPC-SL) and sodium dodecyl sulfate(SDS) were set as the independent variables;the dissolution of aprepitant capsules at 15min and 30min, and the dissolution after accelerated at 40℃ and 75% RH for 6 months were set as the dependent variables. Quadratic polynomial mathematic models were used to evaluate the relation-ship between the independent and the dependent variables. According to the mathematic models,an effect graph was drawn. The opti-mized formula was chosen from the overlap of the contour graphs of the dependent variables. The similarity of in vitro dissolution curve was evaluated by using f2factor. Results:The correlation coefficient of quadratic polynomial mathematic model and the reliability was high. The measured values of the optimized formula were within the expected ranges. Conclusion: Aprepitant nanocapsules with the optimized formula by central composite design-response surface methodology meet the requirements. The results can provide evidence for the next industrial production.

Mechanistic study of epidermal growth factor receptor inhibitor-related pruritus / 中国比较医学杂志

Objective The aim of this study was to investigate the mechanism underlying pruritus by comparing the epidermal growth factor receptor inhibitor(EGFRI)-erlotinib mouse model with the substance P(SP)-induced pruritus mouse model. Methods Two randomized groups of mice were treated with erlotinib or SP to induce pruritus. Behavioral and skin manifestations were observed. Pathological images and neurokinin 1 receptor(NK-1R)expression of the skin were determined. Concentration of interleukin(IL)-31, IL-33, histamine, leukotriene B4, and SP was analyzed by enzyme-linked immunosorbent assay. Nitric oxide was analyzed by colorimetry. Results Transient pruritus induced by erlotinib appeared 2 to 5 days after treatment. In contrast, continuous pruritus was observed during the first hour, but was then gradually relieved. These two shared similar scratching behavior. Concentration of neurotransmitters showed similar trends in changes among the erlotinib group and SP group. Immunohistochemical expression was also consistent between the erlotinib group and SP group. Conclusions Erlotinib-associated pruritus is related to release of signaling factors through the SP/NK-1R signaling pathway.

Clinical analysis of aprepitant for treating vomiting caused by cis-platin regimen / 重庆医学

Objective To investigate the clinical efficacy of aprepitant in the treatment of cisplatin based chemotherapy in-duced nausea and vomiting.Methods The tumor patients treated with cisplatin(80 mg/m2)chemotherapeutic regimen in Affiliated Shantou Hospital of Sun Yat-Sen University from December 1,2014 to December 1,2016 were selected,61 cases still had vomiting after using granisetron and dexamethasone for routinely stopping vomiting,the patients with aprepitant and dexamethasone for fur-ther stopping vomiting served as the aprepitant group,while the patients with granisetron and dexamethasone as the granisetron group.Then the complete response(CR)rates within 24,24-72,>72-144 h were observed in the two groups.Results The CR rates within 24 h in the aprepitant group and granisetron group were 66.67% and 51.61% respectively,the difference was not sta-tistically significant(P=0.232),which at 24-72 h were 80.00% and 54.84% respectively,the aprepitant group was significantly better than the granisetron group(P=0.036),which at >72-144 h were 86.67% and 64.52% respectively,the aprepitant group was better than the granisetron group(P=0.045).The comparison of adverse reactions between the two antiemetic drugs found that constipation,diarrhea,urticaria,fatigue and anxiety had no significant difference(P>0.05),the occurrence rate of total adverse reactions in the aprepitant group was 23.33%,which in the granisetron group was 25.81%,the difference between the two groups was not statistically significant(P>0.05).Conclusion Aprepitant combined with dexamethasone has better effect for treating hy-peremetic chemotherapy drug cisplatin chemotherapy caused nausea and vomiting with good tolerance.

Simultaneous determination of fosaprepitant and its metabolite aprepitant in human plasma by liquid chromatography-tandem mass spectrometry / 药学学报

An LC-MS/MS method was developed for the simultaneous determination of fosaprepitant and aprepitant in human plasma, and applied to a pharmacokinetic study of 150 mg fosaprepitant dimeglumine injection to 12 Chinese healthy volunteers. The analytes and internal standards were extracted from plasma by protein precipitation with acetonitrile and separated on a Cortex C18+ (50 mm×2.1 mm, 2.7 μm) column using a gradient elution procedure. Mass spectrometry was performed in negative MRM mode, and parent-to-produce transitions were as follows:m/z 613.1→78.9 for fosaprepitant, m/z 617.0→78.9 for d4-fosaprepitant, m/z 533.2→275.1 for aprepitant and m/z 537.2→279.1 for d4-aprepitant. Plasma sample was basified to stabilize fosaprepitant. The standard curves were demonstrated to be liner in the range of 15.0 to 6 000 ng·mL-1 for fosaprepitant and 10.0 to 4 000 ng·mL-1 for aprepitant. The intra-day precisions and inter-day precisions and accuracy were within the acceptable limits for all concentrations.

Curative Effect of Aprepitant Preventing CINV / 中国肺癌杂志

BACKGROUND@#Chemotherapy is the most important method for cancer treatment. However, chemotherapy induced nausea and vomiting (CINV) has a profound effect on patients. In recent years, there have been new antiemetic drugs, such as aprepitant. We review the curative effect of aprepitant with tropisetron and dexamethasone for prevention of nausea and vomiting in patients receiving Cisplatin chemotherapy.@*METHODS@#Observation is divided into three stages. Whole study phase (0-120 h after chemotherapy administration), acute phases (0-24 h), and delayed phase (24 h-120 h). The primary endpoints were complete response (CR) and complete prevention (CP) during the three different study phase.@*RESULTS@#In the whole study phase, 86.02% of patients achieved CR; in acute phases and delayed phases were 89.25%, 87.1%, respectively. CP were 46.22%, 83.87%, 45.16%, respectively. Anti-CINV effect was significantly associated with age distribution (P=0.008).@*CONCLUSIONS@#Aprepitant with tropisetron and dexamethasone prevented effectively CNIV for patients receiving Cisplatin chemotherapy. This combination could improve the quality of life and the compliance of patient with chemotherapy.

Synthesis of the related substances of aprepitant / 国际药学研究杂志

Objective To synthesize four related substances:1b,1c,1d,and 1e according to the synthetic process of aprepi-tant and its quality standard of USP and EP. Methods The impurities 1b,1c,and 1d were synthesized from 3,5-bis(trifluoromethyl) acetophenone through asymmetrical catalytic reduction reaction,condensation reaction,Grignard reaction ,catalytic hydrogenation and substitution. The impurity 1e was synthesized from(R)-α-methylbenzylamine through 7 reaction steps including esterification,reduc-tion,condensation ect. Results All the four related substances were confirmed by LC-MS and NMR. The results indicated that purity of the product surpassed 95%through HPLC. Conclusion These related substances can be taken as the references for the quality con-trol of aprepitant.

Aprepitant therapy for prevention of moderately chemotherapy-induced nausea and vomiting in patients with gastrointestinal cancer / 上海交通大学学报（医学版）

Objective · To investigate antiemetic effect of aprepitant for moderately chemotherapy-induced nausea and vomiting in patients with gastrointestinal cancer. Methods · From 2014 July to 2015 August, 130 cases of gastrointestinal cancer patients were collected in Ruijin Hospital affiliated to Shanghai Jiao Tong University School of Medicine, who received moderate emetogenic risk of chemotherapy for at least four courses. One hundred and nine patients were treated with aprepitant, palonosetron and dexamethasone on day 1, and aprepitant and dexamethasone on day 2 and 3. Twenty-one patients only received aprepitant and dexamethasone on day 1 and dexamethasone on day 2 and 3 in the first course of chemotherapy. During subsequent courses of chemotherapy they received aprepitant and treated in the same way as 109 patients. MASCC antiemetic tool (MAT) was used to evaluate the intensity of nausea. The primary endpoint was complete response (CR, no emesis and use of no rescue antiemetics) during the overall study phase (0-120 h after chemotherapy) at the second course. The secondary endpoint was complete protection (CP, CR plus no significant nausea) during the overall, acute (0-24 h), and delayed (24-120 h) phases at the second course. Results · The CR rates were 90.0%, 94.6% and 90.8% of patients in the overall, acute and delayed phases, respectively. The corresponding CP rates were 83.8%, 87.8% and 84.6 %, respectively. The CR rate increased from 42.9% to 57.1% during acute phase and increased from 9.5% to 90.5% during delayed phase for 21 patients after treatment with aprepitant. The main adverse reactions include constipation, anorexia and hiccups. Conclusion · Aprepitant combined with palonosetron and dexamethasone can effectively prevent moderately chemotherapy-induced nausea and vomiting in patients with gastrointestinal cancer. Aprepitant therapy can effectively maintain antiemetic effect in patients with many chemotherapy courses.

Simultaneous Determination of 6 Residual Organic Solvents in Aprepitant Raw Material by Headspace Capillary GC / 中国药房

OBJECTIVE:To establish a method for simultaneous determination of 6 residual organic solvents in aprepitant raw material as methanol,ethanol,acetone,isopropyl alcohol,methyl tert-butyl ether and tetrahydrofuran.METHODS:Headspace capillary gas chromatography was adopted.The determination was performed on DB-624 capillary column using temperature programming.The temperature of injector port was 180 ℃,and flame ionization detector was used with temperature of 260 ℃.Nitrogen was used as carrier gas with flow rate 3.0 mL/min.The spilt ratio was 5 ∶ 1,and head-space injection volume was 1.0 mL.The head-space equilibrium temperature was set at 80 ℃,and equilibrium time was 40 min.RESULTS:The linear ranges of methanol,ethanol,acetone,isopropyl alcohol,methyl tert-butyl ether,tetrahydrofuran were 6.052-605.232 μ g/mL (r=0.999 9),9.987-998.718 μg/mL(r=0.999 9),9.998-999.768 μg/mL(r=0.999 8),9.986-998.634 μg/mL(r=0.999 9),9.991-999.090 μg/mL (r=0.999 7),1.461-146.133 μg/mL(r=0.999 5),respectively.The limits of quantitation were 1.782 1,2.079 0,0.749 8,1.777 8,0.223 1,0.607 0 μg/mL;the limits of detection were 0.594 0,0.693 0,0.249 9,0.592 6,0.074 4,0.202 3 μg/mL,respectively.RSD of precision test was lower than 2.0％.Only acetone and isopropyl alcohol were detected in stability test and reproducibility tests,RSD＜2.0％.Their recoveries were 99.34-100.75％ (RSD=0.52％,n=9),98.20％-100.24％ (RSD=0.69％,n=9),98.07％-100.07％ (RSD=0.84％,n=9),99.86％-101.32％ (RSD=0.58％,n=9),97.87％-104.02％ (RSD=2.13％,n=9),98.26 ％-100.58 ％ (RSD =0.75 ％,n =9),respectively.CONCLUSIONS:The established method is simple,accurate and reproducible,and can be used for simultaneous determination of 6 residual organic solvents in aprepitant raw material.

Aprepitant as secondary prevention in moderate-severe vomiting caused by AC chemotherapy for breast cancer / 药学实践杂志

Objective To evaluate the efficacy and side effects of combination therapy with aprepitant ,tropisetron and dexamethasone in the prevention of nausea and vomiting induced by AC chemotherapy in patients after breast cancer surgery . Methods 72 breast cancer patients were selected for this study .Those patients were admitted to the Oncology Department in Dezhou Municipal Hospital from January 2015 to May 2016 .The patients were randomly divided into observation group (35 ca-ses) and control group (37 cases) .All patients underwent breast cancer surgery and followed by AC program for the first time chemotherapy .Chemotherapy induced nausea and vomiting (CINV) were rated moderate to severe during the course of chemo-therapy .The patients in the observation group were treated with aprepitant ,tropisetron hydrochloride and dexamethasone to prevent CINV .The control group was treated with tropisetron hydrochloride and dexamethasone .The efficacy and adverse re-actions in acute phase (0~24 h) and delay phase (24~120 h) were recorded .Results There was no significant difference in the complete control rate (CR) between the two groups during acute phase (P>0 .05) .The observation group had significantly higher effective control rate (CR+PR) in acute phase compared to the control group (P<0 .05) .Both CR and CR+ PR were statistically higher in observation group during delay phase (P<0 .05) .The main adverse reactions in two groups were consti-pation ,fatigue ,facial flushing ,anxiety and dizziness .Those side effects are considered as mild and tolerable .Conclusion Tri-ple antiemetic therapy including aprepitant has good efficacy and reasonable cost to effect ratio for patients received AC chemo-therapy after breast cancer surgery with moderate-severe vomiting .This treatment is easy to accept for those patients .

Manifestation and therapies of EGFRI-induced dermatological toxicities / 中国肿瘤临床

In the past decades, the advent of molecular targeted agents has been a considerable breakthrough for cancer patients, ex-cept for traditional operation, chemotherapy, and radiotherapy. As a novel therapeutic method, molecular targeting treatment is im-portant in the field of medical oncology, in which epidermal growth factor receptor inhibitors (EGFRIs) have been widely used as target-ed agents. Dermatological toxicities are the common side effects associated with the EGFRIs. Diarrhea, weakness, and pneumonia can be observed. EGFRI-induced dermatological toxicities may disrupt the health-related quality of life and cause anticancer treatment dose adjustments or discontinuance. The dermatological toxicities mainly involve rash acneiform, pruritus, xerosis, paronychia, hair change, and skin hypersensitivity. Treatment recommendations from guidelines include antibiotics, corticosteroids, and antihista-mines, but their clinical therapeutic efficacy have not been proven. Therefore, oncologists and dermatologists are investigating effec-tive medication. This article reviews the advances in the study of the clinical manifestations and drug therapies of EGFRI-induced der-matological toxicities to provide reference for clinical practitioners.

A New Drug Antiemetic:Neurokinin I Receptor Antagonist Fosaprepitant / 中国药师

Neurokinin I receptor antagonist (NK1RA) fosaprepitant is a new antiemetic drug. Fosaprepitant dimeglumine was ap-proved by FDA in January 2008, while it is still in the approval stage in China. Fosaprepitant, as a prodrug of aprepitant, is rapidly converted to aprepitant after intravenous administration in vivo. The indication of fosaprepitant is the prevention of chemotherapy in-duced nausea and vomiting ( CINV) , especially the delayed CINV. Fosaprepitant as a unique intravenous preparation overcomes the drawbacks of aprepitant with oral administration only. Its bioavailability is not affected by the vomiting of patients. It is also suitable for patients with oral mucositis, who are unfavorable for oral medication. The action mechanisms, pharmacokinetics, and clinical trials of fosaprepitant were reviewed in the paper.

The substance P/NK-1 receptor system: NK-1 receptor antagonists as anti-cancer drugs.

The substance P (SP)/neurokinin (NK)-1 receptor system plays an important role in cancer. SP promotes the proliferation of tumour cells, angiogenesis and the migration of tumour cells. We review the involvement of SP, the NK-1 receptor and NK-1 receptor antagonists in cancer. Tumour cells overexpress NK-1 receptors, which are involved in their viability. This overexpression suggests the possibility of specific treatment against tumour cells using NK-1 receptor antagonists, thus promoting a considerable decrease in the side effects of the treatment. This strategy opens up new approaches for cancer treatment, since these antagonists, after binding to their molecular target, induce the death of tumour cells by apoptosis, exert an antiangiogenic action and inhibit the migration of tumour cells. The use of NK-1 receptor antagonists such as aprepitant (used in clinical practice) as antitumour agents could be a promising innovation. The value of aprepitant as an antitumour agent could be determined faster than for less wellknown compounds because many studies addressing its safety and characterization have already been completed. The NK-1 receptor may be a promising target in the treatment of cancer; NK-1 receptor antagonists could act as specific drugs against tumour cells; and these antagonists could be new candidate anti-cancer drugs.