Short-term efficacy and influencing factors of conventional chemotherapy combined with irinotecan in patients with advanced gastric cancer

BACKGROUND Gastric cancer is one of the most common cancers worldwide, with a 5-year survival rate of only 20%. The age of onset of gastric cancer is in line with the general rule of cancer. Most of them occur after middle age, mostly between 40and 60 years old, with an average age of about 50 years old, and only 5% of patients are under 30 years old. The incidence of male is higher than that of female.AIM To investigate the short-term efficacy and influencing factors of chemotherapy combined with irinotecan in patients with advanced gastric cancer.METHODS Eighty patients with advanced gastric cancer who were treated in our hospital from January 2019 to January 2022 were selected. The patients were divided into an observation group(n = 40) and control group(n = 40) by the envelope method.The control group was given preoperative routine chemotherapy. The observation group was treated with irinotecan in addition to the chemotherapy given to the control group. The short-term efficacy of treatment in the two groups, as well as tumor marker levels and quality of life before and after treatment were evaluated.RESULTS The short-term treatment effect in the observation group was better than that in the control group(P < 0.05), and the total effective rate was 57.50%. The age and proportion of tumor node metastasis(TNM) stage IV patients with ineffective chemotherapy in the observation group were(65.12 ± 5.71) years and 52.94%,respectively, which were notably higher than those of patients with effective chemotherapy(P < 0.05), while the Karnofsky Performance Scale score was(67.70± 3.83) points, which was apparently lower than that of patients with effective chemotherapy(P <0.05). After 3 mo of treatment, the SF-36 scale scores of physiological function, energy, emotional function, and mental health in the observation group were 65.12 ± 8.14, 54.76 ± 6.70, 47.58 ± 7.22,and 66.16 ± 8.11 points, respectively, which were considerably higher than those in the control group(P < 0.05). The incidence rates of grade Ⅲ-Ⅳ diarrhea and grade Ⅲ-Ⅳ thrombocytopenia in the observation group were 32.50% and 25.00%, respectively, which were markedly higher than those in the control group(P < 0.05).CONCLUSION Chemotherapy combined with irinotecan in patients with advanced gastric cancer has a good short-term efficacy and can significantly reduce serum tumor markers and improve the quality of life of patients. The efficacy may be affected by the age and TNM stage of the patients, and its long-term efficacy needs further study.

Research on Liposomal Irinotecan in Combination with 5-FU/LV for Metastatic Pancreatic Ductal Adenocarcinoma

Objective To systematically review the published clinical and economic research on liposomal irinotecan in combination with 5-FU/LV for metastatic pancreatic ductal adenocarcinoma(mPDAC)at home and abroad.Methods PubMed,Cochrane Library,Embase,CBM,CNKI,Wan Fang data,CRD database and health technology assessment official websites were searched to collect clinical and economic studies on liposomal irinotecan for mPDAC.Results and Conclusion Nine clinical studies and four economic studies were included.The result of clinical studies showed that liposomal irinotecan in combination with 5-FU/LV could extend survival with good drug compliance in patients with mPDAC who progressed on prior gemcitabine-based therapy.This agent represented a new treatment option for second-line chemotherapy in these patients.The results of the economic evaluations failed to reach a consistent conclusion due to different economic levels in various countries.

伊立替康(Irinotecan)对SCA3细胞模型的影响

伊立替康(Irinotecan,CPT-11)是一种治疗癌症的化疗药物,主要代谢产物为7-乙基-10羟基喜树碱(7-Ethyl-10-hydroxycamptothecin,SN38).课题组实验筛选结果表明伊立替康对ataxin-3核质转运有潜在影响.通过免疫荧光、微孔过滤分析以及PretoBlue细胞活性检测等方法,探讨伊立替康对ataxin-3质核分离、突变ataxin-3形成的聚集体以及spinocerebellar ataxia type 3(SCA3)细胞活性的影响.结果表明伊立替康在10μM处理浓度时能够减少ataxin-3进入细胞核,但对蛋白聚集体没有影响;伊立替康在0.001μM或100μM处理浓度时,对SCA3细胞具有细胞毒性作用.本研究阐释了伊立替康对SCA3细胞模型的影响,揭示了旧药新靶点,为其他神经退行性疾病的致病机理和治疗药物研发提供新依据.

Irinotecan, a key chemotherapeutic drug for metastatic colorectal cancer

Irinotecan hydrochloride is a camptothecin derivative that exerts antitumor activity against a variety of tumors. SN-38 produced in the body by carboxylesterase is the active metabolite of irinotecan. After irinotecan was introduced for the treatment of metastatic colorectal cancer(CRC) at the end of the last century,survival has improved dramatically. Irinotecan is now combined with 5-fluorouracil,oxaliplatin and several molecularly-targeted anticancer drugs,resulting in the extension of overall survival to longer than 30 mo. Severe,occasionally life-threatening toxicity occurs sporadically,even in patients in relatively good condition who have a low risk of chemotherapyinduced toxicity,often causing the failure of irinotecanbased chemotherapy. Clinical pharmacological studies have revealed that such severe toxicity is related to exposure to SN-38 and genetic polymorphisms in UDPglucuronosyltransferase 1A1 gene. The large interand intra-patient variability in systemic exposure to SN-38 is determined not only by genetic factors but also by physiological and environmental factors. This review first summarizes the roles of irinotecan in chemotherapy for metastatic CRC and then discusses the optimal dosing of irinotecan based on the aforementioned factors affecting systemic exposure to SN-38,with the ultimate goal of achieving personalized irinotecan-based chemotherapy.

Severe irinotecan-induced toxicity in a patient with UGT1A1*28 and UGT1A1*6 polymorphisms

Many studies have demonstrated the impact of UGT1A1 on toxicity of irinotecan. In particular, patients bear-ing UGT1A1*28 (TA 7/7) have a higher risk of severe neutropenia and diarrhea. Based on this, prescribers of irinotecan are advised that patients with UGT1A1*28 (TA 7/7) should start with a reduced dose of irinotecan, although a particular dose is not specified. Research in Asian countries has shown a lower incidence of UG-T1A1*28 (TA 7/7), while UGT1A1*6 (A/A) is more often found and is associated with severe irinotecan-related neutropenia. We report here a case of a metastatic colorectal cancer patient who is heterozygous for the UGT1A1*28 polymorphism (TA 6/7) as well as the UG-T1A1*6 polymorphism (G/A). The patient was treated with FOLFIRI for 9 cycles and underwent two irinote-can dose reductions according to pharmacokinetic data regarding exposure to the active metabolite, SN-38. Simultaneous heterozygous UGT1A1*28 and UGT1A1*6 polymorphisms may produce higher exposure to SN-38 and a higher risk of adverse effects related to irinote-can. Additional studies will be necessary to determine the optimal starting dose of irinotecan for patients with both UGT1A1*28 and UGT1A1*6 polymorphisms.

Predictive effects of bilirubin on response of colorectal cancer to irinotecan-based chemotherapy

AIM: To examine the predictive effects of baseline serum bilirubin levels and UDP-glucuronosyltransferase(UGT) 1A1*28 polymorphism on response of colorectal cancer to irinotecan-based chemotherapy.METHODS: The present study was based on a prospective multicenter longitudinal trial of Chinese metastatic colorectal cancer(m CRC) patients treated with irinotecan-based chemotherapy(NCT01282658). Baseline serum bilirubin levels, including total bilirubin(TBil) and unconjugated bilirubin(UBil), were measured,and genotyping of UGT1A1*28 polymorphism was performed. Receiver operating characteristic curve(ROC) analysis was used to determine cutoff values of TBil and UBil. The TBil values were categorized into > 13.0 or ≤ 13.0 groups; the UBil values were categorized into > 4.1 or ≤ 4.1 groups. Combining the cutoff values of TBil and UBil, which was recorded as Co Bil, patients were classified into three groups. The classifier's performance of UGT1A1*28 and Co Bil for predicting treatment response was evaluated by ROC analysis. Associations between response and Co Bil or UGT1A1*28 polymorphism were estimated using simple and multiple logistic regression models. RESULTS: Among the 120 m CRC patients, the serum bilirubin level was significantly different between the UGT1A1*28 wild-type and mutant genotypes. Patients with the mutant genotype had an increased likelihood of a higher TBil(P = 0.018) and a higher UBil(P = 0.014) level compared with the wild-type genotype. Patients were stratified into three groups based on Co Bil. Group 1 was patients with TBil > 13.0 and UBil > 4.1; Group 2 was patients with TBil ≤ 13.0 and UBil > 4.1; and Group 3 was patients with TBil ≤ 13.0 and UBil ≤ 4.1. Patients in Group 3 had more than a 10-fold higher likelihood of having a response in the simple(OR = 11.250; 95%CI: 2.286-55.367; P = 0.003) and multiple(OR = 16.001; 95%CI: 2.802-91.371; P = 0.002) analyses compared with the Group 1 individuals. Patients carrying the UGT1A1*28(TA)7 allele were 4-fold less likely to present with a response compared with the individuals harboring a homozygous(TA)6 genotype in the simple(OR = 0.267; 95%CI: 0.100-0.709; P = 0.008) and multiple(OR = 0.244; 95%CI: 0.088-0.678; P = 0.007) analyses. Classifier's performance of Co Bil and UGT1A1*28 were comparable.CONCLUSION: Co Bil and UGT1A1*28 are both independent biomarkers for predicting the treatment response of m CRC patients to irinotecan-based chemotherapy. After validation, Co Bil, an easily determinable index in the clinic, might be helpful in facilitating stratification of m CRC patients for individualized treatment options.

Highly sensitive fluorescence quantification of irinotecan in biological fluids with the aid of second-order advantage

A rapid,green and highly sensitive excitation-emission matrix（EEM） fluorescence method was proposed for analysis of irinotecan（CPT-11） in biological fluids including human plasma and urine samples of uncalibrated interferences with the aid of second-order advantage.Due to the serious spectral overlapping from biological matrices,the parallel factor analysis（PARAFAC） and the alternating normalization-weighted error（ANWE） have been recommended to perform directly calibration and overcome the problem which makes the traditional fluorospectrophotometer in trouble.Satisfactory results can be achieved.Furthermore, performance of the proposed method was evaluated based on figures of merit and some statistical parameters.The accuracy of both algorithms was validated by the elliptical joint confidence region（EJCR） test.The precision and repeatability were also investigated by the relative standard deviations（RSDs） of intra-day and inter-day.

Polyethylene glycol microspheres loaded with irinotecan for arterially directed embolic therapy of metastatic liver cancer

AIM To study tumor response, and tolerability of arterially directed embolic therapy(ADET) with polyethylene glycol embolics loaded with irinotecan for the treatment of colorectal cancer liver metastases(CRC-LM). Secondary objectives were to monitor quality of life, time to progression and survival of patients.METHODS Patients were included in the study if they were affected by CRC-LM, refractory to systemic chemotherapy, treated with ADET using polyethylene glycol embolics, and had liver involvement < 50%. Tumor response, performance status(PS), tumor marker antigens, and quality of life(QoL) were monitored at 1, 3 and 6 mo after ADET. QoL was assessed with the Palliative Performance Scale(PPS).RESULTS We treated 50 consecutive CRC-LM patients with ADET using polyethylene glycol embolics. Their tumor response one month after ADET was: 28% of complete response(CR), 48% of partial response(PR), 8% stable disease(SD), and 16% of progression. Tumor response 3 mo after ADET was CR 24%, PR 38%, SD 19% and progression disease(PD) 19%. Tumor response 6 mo after ADET was CR 18%, PR 44%, SD 21% and PD 18%. QoL was 90% PPS at each time point. Median time to progression for patients who progressed was 2.5 mo(range 0.8-6). Median follow-up was 14 mo(0.8-25 range). ADETs were performed with no complications. Observed side effects(mild or moderate intensity) were: Pain in 32% of patients, increase of transaminase levels in 20% and fever in 14%, whereas 30% of patients did not complain any adverse event. CONCLUSION The treatment of unresectable CRC-LM with ADET using polyethylene glycol microspheres loaded with irinotecan was effective in tumor response and resulted in mild toxicity, and good QoL.

Development of a method to quantify total and free irinotecan and 7-ethyl-10-hydroxycamptothecin(SN-38) for pharmacokinetic and bio-distribution studies after administration of irinotecan liposomal formulation

In 2015,liposomal formulation of irinotecan(ONIVYDE)has been approved by FDA and widely applied in the treatment of pancreatic cancer.ONIVYDE is a novel liposome formulation,entrapping CPT-11 in the aqueous core of vesicles using a modified gradient loading method.Due to toxicity concerns,it is essential to explore a rapid and reliable method to effectively isolate and quantify the non-liposomal,namely,free CPT-11and total CPT-11 in plasma.This study focuses on separation of non-liposomal CPT-11,evaluation of the pharmacokinetics of free CPT-11 and total CPT-11 and bio-distribution after intravenous administration of CPT-11 liposome.Free CPT-11 in plasma was separated by solid-phase extraction(SPE).The amount of total CPT-11 and main metabolite 7-ethyl-10-hydroxycamptothecin(SN-38)in plasma was quantified by ultra-performance liquid chromatography–MS/MS.The calibration curves fitted well and lower limit of quantitation for SN-38,free CPT-11,total CPT-11 and CPT-11 in tissue and were 5 ng/ml,10 ng/ml,4.44 ng/ml and 25 ng/ml respectively.The recoveries,precision and accuracy of the method appear satisfactory.Using this method,the pharmacokinetics and bio-distribution of CPT-11 liposome formulation after an intravenous dose of 2.5 mg/kg were then investigated.

Efficacy of irinotecan-based chemotherapy after exposure to an anti-PD-1 antibody in patients with advanced esophageal squamous cell carcinoma

Objective:Several anti-programmed cell death 1(anti-PD-1)antibodies have demonstrated potential efficacy in the treatment of advanced esophageal squamous cell cancer(ESCC).However,the response to subsequent chemotherapy after the failure of PD-1 blockade in ESCC patients has not been reported,and the optimal sequencing of immunotherapy and chemotherapy remains controversial.The aim of the present study was to evaluate responses to irinotecan-based subsequent chemotherapy in advanced ESCC patients who had progressed after treatment with camrelizumab(SHR-1210),a novel anti-PD-1 antibody.Methods:We retrospectively reviewed the medical records of patients with advanced ESCC treated with camrelizumab at a single institution.Consecutive patients who received subsequent irinotecan-based chemotherapy were selected for data collection and analysis.Results:Overall,a total of 28 patients were included.All patients had received at least two lines of systemic treatment prior to irinotecan salvage.The most common regimen that was administered after PD-1 blockade was irinotecan in combination with 5-fluorouracil(5-Fu)(or its derivatives),which was given to 19 patients.The objective response rate(ORR)and disease control rate(DCR)were 17.9%(5/28)and 64.3%(18/28),respectively,with 5(17.9%)patients achieving a partial response and 13(46.4%)having stable disease.The median progressionfree survival(PFS)was 3.18[95%confidence interval(95%CI),2.48-3.88]months and the median overall survival(OS)was 6.23(95%CI,4.71-7.75)months.No new safety issues,either immune-related or otherwise,were observed.Conclusions:Our results suggested that the response to irinotecan-based chemotherapy after PD-1 blockade in advanced ESCC patients appeared similar to that previously observed in patients who had not received PD-1 antibodies,and further study in larger cohorts or randomized trials is warranted to verify our observation.

Active loading liposomal irinotecan hydrochloride:Preparation,in vitro and in vivo evaluation

The aim of the present study was to investigate the effect of various transmembrane ammonium salt gradients and different lipid composition on the loading efficiency of liposomal formulations of irinotecan hydrochloride(CPT-11),their behavior in vivo and cytotoxicity.Among ammonium salts studied,ammonium sulfate was successfully used to load CPT-11 into liposomes with the highest encapsulation efficiency.Subsequently,liposomal CPT-11 with different lipid composition was prepared by ammonium sulfate gradient method.CPT-11 can be loaded to a level over 90%into liposomes composed of soybean phospholipids/cholesterol(SPC-L)or hydrogenated natural soybean phospholipids/cholesterol(HSPC-L).In vitro release profiles were also investigated,indicating that HSPC-L had a lower release than that in SPC-L.In vivo,encapsulation of CPT-11 in both liposomal formulations showed higher area under the curve(AUC),a lower rate of clearance(CL)and smaller volume of distribution for CPT-11 than those of irinotecan hydrochloride solution(CPT-11-S).However,CL and AUC of 7-ethyl-10-hydroxycamptothecin(SN-38)were moderately improved in HSPC-L group.Based on the results of comparative pharmacokinetics of liposomal CPT-11 with different lipid composition,the in vitro cytotoxicity of HSPC-L was evaluated with human tumor cell.The result indicated that liposomal CPT-11 showed a great enhancement in vitro cytotoxicity.The results suggested that entrapment of CPT-11 in liposomes especially in those with high phase-transition temperature lipid by ammonium sulfate gradient would be a promising formulation with a better in vivo behavior.

槲皮素结合Irinotecan或SN-38治疗或许对胃癌细胞的生长有抑制作用

目前尚无槲皮素结合irinotecan／SN-38治疗胃癌（GC）的研究报道。本文研究的目的是探讨槲皮素结合iri—notecan／SN-38能否更有效地降低癌细胞转移相关基因和蛋白质的表达，并减缓GC的发展。对象与方法：①体外研究。将经培养后的人类胃癌细胞（AGS）分别放入槲皮素（6．25，12．5，25，50，100μM）、SN-38（2．5，5，25，50，100nM）和槲皮素＋SN-38中进行48h等处理后.

Pharmacogenetics of irinotecan:An ethnicity-based prediction of irinotecan adverse events

Irinotecan is now regarded as the most active drug for the treatment of colorectal cancer.However,one of the most difficult issues oncologists face is deciding the optimal dose for an individual patient,as each individual shows different outcomes even at the same dose with regard to treatment related adverse events,ranging from no toxicity to a lethal event.Inherited genetic polymorphism of a single gene or multiple genes(haplotype or linkage disequilibrium) involved in SN-38 glucuronidation,a predominant route of irinotecan detoxification,is now recognized as a significant factor that can alter the incidence of side effects.Attempts to explore such inherited genetic variability have been focused on elucidating interindividual as well as interethnic differences.Genotyping studies in relation to adverse events in an individual or in a group of similar ethnicity should contribute to establishing individualoriented or ethnicity-oriented irinotecan treatment regimens.This review highlights current single-or multi-tired approaches for the elucidation of genetic predispositions of patients to severe toxicities,especially among Asians.The purpose of this is to contribute to minimizing toxicity by dose modifications,with the consequent aim of maximizing dose intensity and efficacy,an ultimate goal of irinotecan-individualized therapy.

Raltitrexed + irinotecan as second-line chemotherapy in elderly patients with advanced colorectal cancer

Aims and Background: Irinotecan is a standard option for relapsed/refractory advanced colo- rectal cancer. Combination with raltitrexed and irinotecan at lower than MTD doses should preserve disease stabilisation while decreasing toxicity. Patients and Methods: From January 2004 to April 2009, we analyzed, retrospectively, our data on irinotecan + raltitrexed, fixed doses, as a second-line chemotherapy in elderly pa- tients (>70 years) with advanced colorectal can- cer after failure of oxaliplatin based chemothera- py twenty-three patients were evaluated. Iri- notecan 350 mg + raltitrexed 2.6 mg were given every 3 weeks. Tumo r measurements were ob- tained after every third course of therapy. Toxic- ity was assessed weekly using the National Cancer Institute Common Toxicity Criteria, ver- sion 2. Results: The median number of treatment courses received per patient was 4 (range, 1 - 8). All pa-tients were assessable for toxicity and 21 for response. The most frequently observed severetoxicities were diarrhea (grade 2, 13%) No cases of significant neutropenia occurred. Ob- jective partial responses were observed in 3 pa- tients (13%). An additional 10 patients (43%) had stable disease as their best response. To date, 12 patients have progressed with a median time- to-progression of 4.3 months and a median sur- vival of 8.3 months. Conclusions: A three weekly irinotecan + raltitrexed administration can indu- ce tumor control in elderly patients with advanc- ed colorectalcancer that has progressed during or shortly after oxaliplatin-based chemotherapy. The diarrhea by irinotecan, seems mitigated by coad-ministration of a smaller dose of

Phase 1/2 study of concurrent chemoradiotherapy with weekly irinotecan hydrochloride for advanced/recurrence uterine cancer:A multi-institutional study of Kansai Clinical Oncology Group

Objective:Concurrent chemoradiotherapy using cisplatin was thought to be standard treatment for squamous cell carcinoma of cervix,but it had not been effective for adenocarcinoma.Concurrent chemoradiotherapy using irinotecan hydrochloride(CPT-11)had been effective for colorectal cancer,thus,we chose CPT-11 as a candidate for gynecologic adenocarcinoma.To evaluate the maximum tolerated dose(MTD)of weekly CPT-11 with external pelvic radiotherapy,a phase 1/2 study was conducted according to modified Fibonacci method.Methods:Eligible patients were advanced uterine cancer with measurable diseases[performance score(PS):0-2].Study period was from August 1 st,2002 to December 31 st,2008.The starting dose level(DL)of CPT-11 was 30 mg/m2(DL1)given weekly for 4 weeks.Subsequently,dose escalation was scheduled in 10 mg/m2 increments to 60 mg/m^2(DL4).The fixed radiotherapy consisted of whole pelvic 1.8 Gy/d,once a day in weekday for five weeks and it amounted to 45 Gy(25 fractions)in total.Results:Seventeen patients were enrolled.As for toxicities,one(1/17:5.9%)grade(G)4 neutropenia lasting 7 days had been seen in DL4.G2 diarrhea was identified in 35.3%(6/17)of the patients,and 11.8%(2/17)G3 diarrhea was observed in DL3 and DL4.Thus,the MTD of CPT-11 was defined as dose of 60 mg/m^2.The recommended dose was decided as 50 mg/m^2.The response rate was 88.2%[9 complete response(CR),3 partial response(PR),3 stable disease(SD),2 not evaluable(NE)].Disease control rate at 1 month after treatment completion was 100%but distant metastases were found in 24%(4/17)in longer outcome.Conclusions:MTD was 60 mg/m^2 and recommended dose was set as 50 mg/m2.This concurrent chemoradiation using weekly CPT-11 was feasible at 50 mg/m^2,and it might be effective even in adenocarcinoma of the uterus.

Phase II Study of Irinotecan plus S-1 in Treatment of Advanced Gastric Cancer

Objective: The efficacy and safety of irinotecan hydrochloride (CPT-11) plus oral fluoropyrimidine S-1 combination therapy in patients with previously untreated advanced gastric cancer was evaluated. Methods: The regimen comprised CPT-11 plus S-1: CPT-11, 60 mg/m2 (days 1, 15);S-1, 40 - 60 mg/body twice daily (days 1 - 21) followed by a 1-week rest, every 4 weeks. Primary endpoint was response rate. Secondary endpoints were tumor control rate, adverse events, relative dose intensity, and overall survival. Results: Twenty-five patients were enrolled;median age was 66 years. Response rate was 40% (95% confidence interval, 21.1% - 61.3%;complete response in 1;partial response in 9). Tumor control rate was 56.0%, median survival time was 436 days and relative dose intensities were 0.83 for CPT-11 and 0.85 for S-1. Incidence of grade 3 or greater neutropenia, anemia and diarrhea was 16%, 12%, and 12%, respectively.Conclusion: The present results indicate that CPT-11 plus S-1 offers lower treatment-related toxicity than regimens including cisplatin and is effective in patients with advanced gastric cancer.

A Single Institutional Phase II Randomized Trial of Whole Brain Radiation Therapy with or without Irinotecan for the Treatment of Brain Metastases from Solid Tumours

Background: The relatively suboptimal results of whole brain radiation therapy (WBRT) alone in eradication of brain metastases and an attempt to improve outcomes with WBRT have led to studies combining radiotherapy with chemotherapy drugs that could act as radiosensitizers with a rationale of improving local tumor control. Materials and Methods: This randomized phase II study evaluated the use of Irinotecan concomitant with 37.5 Gray (Gy) of WBRT in 2.5 Gy daily fractions × 5 days each week for 3 weeks versus Whole WBRT alone in patients with brain metastasis (BM) from solid tumors. Fifty patients were randomized to receive either WBRT alone or concomitant with three irinotecan IV infusions 80 mg/m2, 2 hrs before RT on days 1, 8, and 15. Results: The objective response rate (ORR) was significantly improved in patients receiving Irinotecan with radiotherapy versus radiotherapy alone (48% vs. 28%;p = 0.048). The median time to progression of brain metastasis was significantly longer in the irinotecan and WBRT arm as compared to the WBRT arm (8 vs. 5 months;p < 0.001). There was no significant difference in survival between treatment arms (p = 0.361). Irinotecan with radiotherapy was generally well tolerated and did not interfere with the delivery of WBRT. Conclusions: Irinotecan concomitant with WBRT was well tolerated and significantly improved local control of BM compared with WBRT alone. These findings require confirmation in a phase III trial with addition of quality of life assessment.

A Network Pharmacology Approach to Investigate the Mechanisms of Huangqin Decoction in the Treatment of Irinotecan-Induced Gastrointestinal Toxicity

Objective:To find out the potential mechanisms of Huangqin decoction in the treatment of irinotecan-induced gastrointestinal toxicity.Methods:A network pharmacology approach was used to analyze the active compounds,drug targets and interacting pathways of Huangqin decoction in treating irinotecan-induced gastrointestinal toxicity.The compounds and predicted targets of Huangqin decoction were screened from TCMSP,and the disease targets were obtained from GeneCards.The therapeutic mechanisms of action of the Huangqin decoction were analyzed by gene ontology(GO)enrichment,Kyoto encyclopedia of genes and genomes pathway(KEGG)enrichment analyses.Results:The results show that 161compounds and 143 targets were obtained in this work.These targets were further mapped to 216 GO biological process terms and 30 remarkably pathways.Active compounds,targets,and pathways were used to construct a compound-target network.These results indicated that Huangqin decoction may treat the irinotecan-induced gastrointestinal toxicity mainly from intervening in the mucosal inflammation,cell apoptosis process,and cell proliferation.Conclusion:This study confirmed that the active components of Huangqin decoction play an important role in the treatment of irinotecan-related gastrointestinal toxicity through multi-target and multi-pathway,which provides a new way for the pathogenesis of irinotecan-related gastrointestinal toxicity.It facilitates the modernization of herbal medicine for complex diseases in the future.

A Randomized Controlled Clinical Study of Irinotecan/cisplatin Regimen and Etoposide/cisplatin Regimen in the First-line Treatment of Small Cell Lung Cancer

Objective:This paper mainly study on the effects of irinotecan/cisplatin and etoposide/cisplatin regimens in the treatment of small cell lung cancer.Methods:50 cases of small cell lung cancer patients in our hospital were divided into control group and experimental group and administered with etoposide/cisplatin and irinotecan/cisplatin regimen,and the treatment effects of the two regimens were compared statistically.Results:After treatment,both groups achieved high treatment efficiency,and the incidence of toxic side effects was low,with no significant difference(P>0.05);serological ABCG2 and FGFBP1 level indicators were better than the control group,both showing significant differences(P<0.05).Conclusions:Irinotecan has achieved better improvement in serological indicators in the first-line treatment of small cell lung cancer,with no significant difference in short-term treatment efficiency.