Adjuvant chemotherapy with paclitaxel and cisplatin in lymph node-positive thoracic esophageal squamous cell carcinoma

Objective： No standard postoperative adjuvant chemotherapy has ever been established in node-positive esophageal squamous cell carcinoma （ESCC）. This is a study to explore the effect of postoperative paelitaxel （PTX） and cisplatin （DDP） in lymph node-positive, completely resected thoracic ESCC patients. Methods： We conducted a prospective phase II trial. Patients had pathologically node-positive thoracic ESCC with negative margins. Outcomes of disease-free survival （DFS） and overall survival （OS） were compared with a matched historical control cohort. The postoperative chemotherapy regimen consisted of 4 to 6 cycles of PTX 150 mg/m2 administered intravenously on d 1 followed by DDP 50 mg/m2 on d 2 every 14 d. Results： Forty-three patients were accrued from December 2007 to May 2012 at Cancer Hospital of Chinese Academy of Medical Sciences for adjuvant chemotherapy. The historical control group consisted of 80 patients who received complete resection but no adjuvant chemotherapy during the same period of time. Of the 43 patients with adjuvant chemotherapy, 37 （86.0%） patients completed 4 to 6 cycles of chemotherapy. The 3-year DFS rates were 56.3% in the adjuvant group and 34.6% in the control group （P=0.006）. The 3-year OS rates were 55.0% in the adjuvant group and 37.5% in the control group （P=0.013）. Multivariate analysis revealed that postoperative chemotherapy was the significant predictor for improved OS （P=0.005）. Conclusions： Biweekly adjuvant PTX and DDP might improve 3-year DFS and OS in lymph node-positive, curatively resected thoracic ESCC patients. These conclusions warrant further study in randomized phase III clinical trials.

Feasibility Study for Biweekly Administration of Cisplatin plus Vinorelbine as Adjuvant-Chemotherapy for Completely Resected Non-Small Cell Lung Cancer Patients in a Japanese Population

Purpose: To evaluate the feasibility of biweekly administration of cisplatin and vinorelbine as adjuvant chemotherapy for patients with completely resected non-small cell lung cancer (NSCLC). Patients and Methods: This was a single-arm, single-institutional study. Patients with completely resected NSCLC (p-Stage IB-IIIA) with no previous chemotherapy or radiotherapy were eligible. Simon’s optimal two-stage design was applied. Both cisplatin (50 mg/m2) and vinorelbine (25 mg/m2) were given on days 1 and 15, every 28 days. The primary endpoint of this study was the feasibility of this combination in the four cycles of treatment. Results: Twenty patients (19 lobectomies and 1 pneumonectomy) were enrolled in this study. 10 (50%) of patients had grade 3/4 neutropenia, and 3 (15%) had grade 3/4 anemia. Severe non-hematologic toxicities were uncommon in this series. No treatment-related death was encountered. 18 (90%) patients completed the planned 4 cycles of chemotherapy. The median intensity was 24.3 (range 18.1 to 25) mg/m2/week with an average of 23.6 (21 - 25) mg/m2/week cisplatin and 12.5 (range 10 to 12.5) mg/m2/week with an average of 12.3 (10 - 12.5) mg/m2/week vinorelbine. The median relative dose intensity of cisplatin was 97.5% (range 72.5% to 100%) with an average of 94.6% (72.5% - 100%) and that of vinorelbine was 100% (range 80% to 100%) with an average of 97.8% (80% - 100%). Conclusion: This regimen is feasible in the treatment of patients with completely resected NSCLC. A phase III trial is warranted to assess the efficacy of this regimen at promoting survival and preventing recurrence.

PhaseⅡstudy of induction chemotherapy followed by concurrent chemoradiotherapy with raltitrexed and cisplatin in locally advanced nasopharyngeal carcinoma

Objective:For locally advanced nasopharyngeal carcinoma(LA-NPC)patients,high incidences of distant metastases and severe treatment related toxicities are the main obstacles needed to be overcome.Raltitrexed,a specific thymidylate synthase inhibitor with a convenient administration schedule,has an acceptable and manageable toxicity,and possesses radio-sensitizing properties.To investigate the efficacy and safety of raltitrexed and cisplatin induction chemotherapy and concurrent chemoradiotherapy(IC+CCRT)in patients with LA-NPC,a phaseⅡclinical study was conducted.Methods:Sixty eligible patients with LA-NPC were enrolled into this study.A raltitrexed-cisplatin combination was used as part of an IC+CCRT regimen.Raltitrexed-cisplatin IC was given once every 3 weeks(q3 w)for two cycles,followed by raltitrexed-cisplatin based CCRT q3 w for two cycles.Intensity-modulated radiotherapy(IMRT)was given for all enrolled patients.Results:All patients were included in survival analysis according to the intent-to-treat principle.The objective response rate(ORR)3 months after treatment was 98%.The 2-year overall survival(OS)rate was 92%.The median relapse-free survival(RFS)time was 30.5[95%confidence interval(95%CI),28.4-32.3]months.The 2-year RFS rate was 85%.The 2-year local failure-free survival(LFFS)rate was 97%and the 2-year distant metastasis-free survival(DMFS)rate was 88%.Acute toxicities were mostly grade 2 and 3 reactions in bone marrow suppression,gastrointestinal side effect and oropharyngeal mucositis.Only two patients occurred grade 4 acute toxicities,one was bone marrow suppression and the other was dermatitis radiation.Conclusions:The combination of raltitrexed and cisplatin has a comparable efficacy to those in standard firstline therapy.

Clinical significance of miRNA-106a in non-small cell lung cancer patients who received cisplatin combined with gemcitabine chemotherapy

Objective：Research has demonstrated that microRNA（miR）-106a is related to cisplatin resistance.We investigated the expression of miR-106a in the serum of patients with non-small cell lung cancer（NSCLC）and their sensitivity to chemotherapy by cisplatin combined with gemcitabine.Methods：Eighty-five NSCLC patients,who completed four cycles of gemcitabine and cisplatin chemotherapy,volunteered for this study and their serum samples were collected.Serum samples from 60 healthy subjects were used as controls.Real-time quantitative polymerase chain reaction（real-time q PCR）was used to quantify the level of miR-106a in the serum.Demographic and survival data of these patients were collected for the analysis.Results：The expression of miR-106a in the serum of NSCLC patients was significantly higher than that of healthy subjects（P＆lt;0.001）.The expression of miR-106a was not correlated with patients＇gender,age,tumor size,lymphatic metastasis,and pathological types;but was correlated with patients＇tumor staging（P=0.003）.After chemotherapy,serum miR-106a expression decreased in patients.The decrease in miR-106a expression in the chemotherapy-sensitive group was much higher than that in the chemotherapy-resistant group.Survival analysis shows that NSCLC patients with high expression of miR-106a have a poorer prognosis.The overall survival of NSCLC patients in the chemotherapy-sensitive group was significantly higher than that in the chemotherapy-resistant group.Conclusions：High expression of miR-106a may be involved in the development of NSCLC.Mi R-106a has significance in the prognosis of NSCLC.The level of miR-106a in the serum can be a useful parameter in screening for drug resistance during cisplatin-based chemotherapy.

Effect of PI3K-mediated autophagy in human osteosarcoma MG63 cells on sensitivity to the chemotherapy drug cisplatin

Objective: To investigate the influence of autophagy on sensitivity to the chemotherapy drug cisplatin(DDP) and the role of PI3 K in autophagy. Methods: MTT methods and l ow cytometer, with rapamycin up-regulating the autophagy and 3-MA down-regulating the autophagy, were employed to measure the proliferation inhibition rate on DDP-treated osteosarcoma cells and the change in cell cycle. The expression of intracellular protein was detected by Western blot. The autophagy of MG63 cell was observed using l uorescence microscope and transmission electron microscope. Results: Western blot showed that basic autophagy level of MG63 cell was significantly lower than that of h FOB cell. MTT test revealed that the cell proliferation inhibition rate in the group treated with rapamycin and DDP, group treated with 3-MA and DDP, and group only treated with DDP was signii cantly dif erent. It was demonstrated by the l ow cytometry that in group treated with DDP, inhibition on autophagy can increase the cell numbers in G1 phase and reduce the cell numbers in S phase of cell cycle. Increase of autophagosome in MG63 cytoplasm was observed under l uorescence microscope. Conclusions: Up-regulating the autophagy signii cantly reduced the sensitivity of MG63 cell to chemotherapy with DDP. DDP induced autophagy of MG63 cell and blocked the cell cycle at G1 phase.

Efficacy of 5-Fluorouracil and High-Concentration Cisplatin Suspended in Lipiodol by Short-Term Hepatic Arterial Infusion Chemotherapy for Advanced Hepatocellular Carcinoma with Portal Vein Tumor Thrombosis

Background: Since advanced hepatocellular carcinoma (HCC) is potentially fatal, and patients’ quality of life (QOL) often deteriorates during their treatment, improving the prognosis and QOL of patients given chemotherapy is very important. In addition, cost-effective treatments are highly desirable when chemotherapy must be given repeatedly. The aim of this study was to evaluate the efficacy and usefulness of 5-fluorouracil (5-FU) and high-concentration cisplatin by short-term hepatic arterial infusion chemotherapy (3-day FPL) in advanced HCC patients. Methods: Thirty patients with unresectable advanced HCC were enrolled. The patients underwent hepatic arterial infusion chemotherapy via the implanted port system with 5-FU on days 1 - 3 and a fine-powder formulation of cisplatin in suspended pre-warmed lipiodol on day 2 every 4 to 10 weeks. Tumor response was assessed one month later with CT. Results: All patients had evidence of portal vein invasion (Vp2-4). Four patients achieved a complete response (CR), 8 patients achieved a partial response (PR), and 7 patients had stable disease (SD). The median progression-free survival (PFS) and overall survival (OS) were 198 days and 452 days, respectively. The OS was significantly longer in the successful disease control group (CR, PR, and SD) than in the progressive disease group (P < 0.005). Conclusions: Three-day FPL was effective and tolerable in advanced HCC patients due to its shorter time of administration than conventional FP therapy. Therefore, repetitive 3-day FPL appears useful and contributes to improving the prognosis and QOL of patients with advanced HCC. In addition, this protocol is a cost-effective treatment.

Successful treatment of multiple lung metastases of hepatocellular carcinoma by combined chemotherapy with docetaxel, cisplatin and tegafur/uracil

We report the successful treatment of multiple lung metastases after hepatic resection for hepatocellular carcinoma (HCC) with combined docetaxel, cisplatin (CDDP), and enteric-coated tegafur/uracil (UFT-E). A 68-year-old man was diagnosed with multiple lung metastases of HCC 7 mo after partial hepatectomy for HCC. Oral UFT-E was given daily and docetaxel and CDDP were given intra-arterially (administered just before the bronchial arteries) every 2 wk via a subcutaneous injection port. One month after starting chemotherapy, levels of tumor marker, protein induced by vitamin K absence(PIVKA--), decreased rapidly,and after a further month, chest X-ray and computed tomography revealed the complete disappearance of multiple liver metastases. Two years after the combined chemotherapy, HCC recurred in the liver and was treated but no pulmonary recurrence occurred. In the absence of a standardized highly effective therapy, this combined chemotherapy with docetaxel, CDDP and UFT-E may be an attractive option for multiple lung metastases of HCC.

Role of ABCG2 expression driven by cisplatin in platinumcontaining chemotherapy for gastric cancer

AIM:To investigate the relationship between increases in expression time of ABCG2 mRNA driven by cisplatin and efficacy of platinum-containing chemotherapy for gastric cancer.METHODS:Tumor specimens and normal control tissues were collected from 78 patients with gastric cancer treated from January 2008 to December 2011.Fresh tumor tissue obtained from the surgically resected specimens was tested within 6 h.Polymerase chain reaction products were run on 2%agarose gels and analyzed under ultraviolet light after ethidium bromide staining.Increases in ABCG2 mRNA expression time cisplatin,and were divided into terciles and compared in relation to clinical outcomes.RESULTS:Among groups classified by expression time of ABCG2 mRNA,no significant differences in baseline clinical characteristics and pathological findings were detected.The median overall time was 14.2(95%CI:9.7-18.6),11.4(95%CI:6.3-16.5)and 8.1(95%CI:5.4-10.8)in patients with low,intermediate and high increases in ABCG2 mRNA expression times(P<0.05),respectively.Median survival associated with performance status and tumor node metastasis(TNM)stage showed a similar trend,with longer survival and higher risk for mortality associated with lower performance status score and TNM stage.In a multivariate analysis for survival with Cox proportional-hazards model,increased ABCG2 mRNA expression time was an independent predictor for overall survival.Overall survival was longer with increased ABCG2 mRNA expression times≤0.71 than increased ABCG2 mRNA expression times>0.71,with a hazard ratio for death of 0.855(95%CI:0.615-0.962,P=0.038).CONCLUSION:Increased ABCG2 mRNA expression time driven by cisplatin is associated with survival of gastric cancer patients,and this may help modify the therapeutic strategies.

Epirubicin,Cisplatin,5-FU combination chemotherapy in sorafenib-refractory metastatic hepatocellular carcinoma

AIM: To evaluate the clinical efficacy and safety of epirubicin, cisplatin, and 5-FU combination chemotherapy for the sorafenib-refractory metastatic hepatocellular carcinoma (HCC).

Docetaxel and cisplatin combination chemotherapy in anthracyclines-resistant advanced breast cancer

Objective： To observe the effect and toxicity of docetaxel with cisplatin in anthracyclines-resistant advanced breast cancer. Methods： Forty-five female patients received docetaxel 60 mg/m^2 on dl and cisplatin 30 mg/m^2 on d1-d3 of every 28 days. Every patient was treated with at least 2 cycles and a median of 3 cycles （2-6 cycles ）. Results： Five patients achieved complete response （11.1%） and 18 partial response （40.0%）, 10 stable disease （22.2%）. The overall response rate was 51.1%. The clinical disease control rate was 73.3%, median time to tumor progression （TTP） was 7.8 months （1.0-34.5 months）, median survival time was 17.6 months （range 1.9-48.0 months）, and one year survival rate was 65.2%. The main side effect was marrow suppression. The treatment was well tolerated with grades Ⅲ and Ⅳ leukopenia in nine （20%） and ten （22.2%） patients. Conclusion： Combinative chemotherapy of docetaxel and cisplatin has a good anti-tumor activity on refractory advanced breast cancer with manageable toxicity.

Effect of double platinum agents, combination of miriplatintransarterial oily chemoembolization and cisplatinhepatic arterial infusion chemotherapy, in patients with hepatocellular carcinoma: Report of two cases

Hepatocellular carcinoma(HCC) is one of the most common cancers and the third highest cause of cancerassociated mortality worldwide. The treatment of HCC is complicated by its variable biological behavior and the frequent coexistence of chronic liver disease, particularly cirrhosis. To date, multiple treatment modalities have been developed according to the stage of the tumor and the hepatic functional reserve, including transarterial treatments such as transarterial chemoembolization, transarterial oily chemoembolization(TOCE), and hepatic arterial infusion chemotherapy(HAIC). We conducted a phase I and II study of the combination therapy with double platinum agents, miriplatin and cisplatin, and confirmed its safety and efficacy. Here, we describe two cases of unresectable HCC who were successfully treated by miriplatin-TOCE/cisplatin-HAIC combination therapy, resulting in complete responses with no significant adverse events. This report will provide that the combination therapy can be the therapeutic option for HCC patients in the advanced stage.

Phase Ⅰ trial of combination chemotherapy with gemcitabine, cisplatin, and S-1 in patients with advanced biliary tract cancer

AIM: To evaluate the dose-limiting toxicities(DLTs)and determine the maximum-tolerated dose(MTD) and recommended dose(RD) of combination chemotherapy with gemcitabine, cisplatin and S-1 which is an oral fluoropyrimidine pro-drug in patients with advanced biliary tract cancer.METHODS: Patients with histologically or cytologically confirmed unresectable or recurrent biliary tract cancer were enrolled. The planned dose levels of gemcitabine(mg/m2), cisplatin(mg/m2), and S-1(mg/m2 per day) were as follows: level-1, 800/20/60;level 0, 800/25/60; level 1, 1000/25/60; and level 2,1000/25/80. In each cycle, gemcitabine and cisplatin were administered intravenously on days 1 and 15,and S-1 was administered orally twice daily on days 1to 7 and days 15 to 21, every 4 wk.RESULTS: Twelve patients were enrolled, and level0 was chosen as the starting dose. None of the first three patients had DLTs at level 0, and the dose was escalated to level 1. One of six patients had DLTs(grade 4 febrile neutropenia, leucopenia, and neutropenia; grade 3 thrombocytopenia) at level 1.We then proceeded to level 2. None of three patients had DLTs during the first cycle. Although the MTD was not determined, level 2 was designated at the RD for a subsequent phase Ⅱ study.CONCLUSION: The RD was defined as gemcitabine1000 mg/m2(days 1, 15), cisplatin 25 mg/m2(days1, 15), and S-1 80 mg/m2 per day(days 1-7, 15-21),every 4 weeks. A phase Ⅱ study is planned to evaluate the effectiveness of combination chemotherapy withgemcitabine, cisplatin, and S-1 in advanced biliary tract cancer.

MicroRNA-218 is upregulated in gastric cancer after cytoreductive surgery and hyperthermic intraperitoneal chemotherapy and increases chemosensitivity to cisplatin

AIM: To investigate the molecular mechanisms of miRNA in advanced gastric cancers (AGCs) before and after cytoreductive surgery (CRS) + hyperthermic intraperitoneal chemotherapy (HIPEC).

Phase Ⅱ study of docetaxel,cisplatin and capecitabine as preoperative chemotherapy in resectable gastric cancer

AIM To investigate the feasibility of preoperative docetaxel,cisplatin and capecitabine(DCC) in patients with resectable gastric cancer.METHODS Patients with resectable gastric cancer fulfilling the inclusion criteria,were treated with 4 cycles of docetaxel(60 mg/m2),cisplatin(60 mg/m2) and capecitabine(1.875 mg/m2 orally on day 1-14,two daily doses) repeated every three weeks,followed by surgery.Primary end point was the feasibility and toxicity/safety profile of DCC,secondary endpoints were pathological complete resection rate and pathological complete response(p CR) rate.RESULTS All of the patients(51) were assessable for the feasibility and safety of the regimen.The entire preoperative regimen was completed by 68.6% of the patients.Grade Ⅲ/Ⅳ febrile neutropenia occurred in 10% of all courses.Three patients died due to treatment related toxicity(5.9%),one of them(also) because of refusing further treatment for toxicity.Of the 45 patients who were evaluable for secondary endpoints,four developed metastatic disease and 76.5% received a curative resection.In 3 patients a p CR was seen(5.9%),two patients underwent a R1 resection(3.9%).CONCLUSION Four courses of DCC as a preoperative regimen for patients with primarily resectable gastric cancer is highly demanding.The high occurrence of febrile neutropenia is of concern.To decrease the occurrence of febrile neutropenia the prophylactic use of granulocyte colonystimulating factor(G-CSF) should be explored.A curative resection rate of 76.5% is acceptable.The use of DCC without G-CSF support as preoperative regimen in resectable gastric cancer is debatable.

Randomized comparison of lobaplatin plus etoposide and cisplatin plus etoposide chemotherapy in patients with extensive-stage small cell lung cancer

Objective： To compare the efficacy and safety of Lobaplatin plus Etoposide （EL） and Cisplatin plus Etoposide （EP） regimens in chemonaive with extensive-stage small-cell lung cancer （SCLC）. Methods： Between July 2010 and July 2011, a total of 62 patients with extensive-stage small-cell lung cancer who received initial treatment in our hospital and 309 hospital of PLA. 31 patients were randomly assigned to the EL Group： Lobaplatin was given intravenously at a dose of 30 mg/m2 on day 1 and Etoposide 100 mg/m2 on days 1 to 3 of 21-day cycles for a maximum of six cycles. Another 31 patients were assigned to the EP Group： Cisplatin was given intravenously at a dose of 75 mg/m2 on day 1 and Etoposide 100 mg/m2 on days 1 to 3 of 21-day cycles for a maximum of six cycles. We evaluated the efficacy, overall response rate （ORR）, disease control rate （DCR）, the progression-free survival （PFS） and toxicity between the patients of the two groups. Results： All 62 patients were eligible. In the EL group, 2 （6.5%） patients had complete response, 20 （64.5%） patients had partial response, 5 （16.1%） patients had stable disease and 4 （12.9%） patients had progress disease. In the EP group, 2 （6.5%） patients had complete response, 22 （70.9%） patients had partial response, 4 （12.9%） patients had stable disease and 3 （9.7%） patients had progress disease. The ORR of EL and EP group were 70.9% and 77.4%, respectively, showing no significant difference （P = 0.562）. The DCR of both groups were 87% and 90%, respectively, showing no significant difference （P = 0.688）. Median PFS of patients with EL and EP regimens were 5.5 months and 5 months, respectively, showing no significant difference （P = 0.637）. Adverse events were observed in all 62 patients. Grade 1 to 4 anemia was higher in the EP group than in EL group, showing significant difference （P = 0.02）. Grade 3 and 4 thrombocytopenia was seen in 4 patients （12.9%） in EL group and 1 patient （3.2%） in EP group. Although one patient had platelet transfusion owing to Grade 4 thrombocytopenia in EL group, no significant difference （P = 0.637） were shown. The incidence of nausea/vomiting was higher in the EP group than in the EL group （96.7% vs 51.6%, P = 0.00）. Conclusien： The EL regimen is an effective and low-toxicity chemotherapy and no inferior to EP regimen in treatment response, therefore, EL regimen maybe is a good choice for patients with extensive-stage SCLC.

Intraarterial chemotherapy with gemcitabine and cisplatin in locally advanced or recurrent penile squamous cell carcinoma

The prognosis of locally advanced or recurrent squamous cell carcinoma(SCC) of the penis after conventional treatment is dismal. This study aimed to evaluate the therapeutic effects of intraarterial chemotherapy with gemcitabine and cisplatin on locally advanced or recurrent SCC of the penis. Between April 1999 and May 2011, we treated 5 patients with locally advanced penile SCC and 7 patients with recurrent disease with intraarterial chemotherapy. The response rate and toxicity data were analyzed, and survival rates were calculated. After 2 to 6 cycles of intraarterial chemotherapy with gemcitabine and cisplatin, 1 patients with locoregionally advanced disease achieved a complete response, and 4 achieved partial response. Of the 7 patients with recurrent disease, 2 achieved complete response, 3 achieved partial response, 3 had stable disease, and 1 developed progressive disease. An objective tumor response was therefore achieved in 10 of the 12 patients. The median overall survival for the patients was 24 months(range, 10-50 months). Three out of 10 patients who responded were long-term survivors after intraarterial chemotherapy. Intraarterial chemotherapy with gemcitabine and cisplatin may be effective and potentially curative in locoregionally advanced or recurrent penile SCC. The contribution of this therapy in the primary management of advanced or recurrent penile SCC should be prospectively investigated.

Prediction of nephrotoxicity induced by cisplatin combination chemotherapy in gastric cancer patients

AIM:To evaluate the treatment options for nephrotoxicity due to cisplatin combination chemotherapy.METHODS:We retrospectively reviewed patients who had received cisplatin combination chemotherapy for gastric cancer between January 2002 and December 2008.We investigated patients who had shown acute renal failure(ARF),and examined their clinical characteristics,laboratory data,use of preventive measures,treatment cycles,the amount of cisplatin administered,recovery period,subsequent treatments,and renal status between the recovered and unrecovered groups.RESULTS:Forty-one of the 552 patients had serum creatinine(SCR)levels greater than 1.5 mg/dL.We found that pre-ARF SCR,ARF SCR,and ARF glomerular filtration rates were significantly associated with renal status postARF between the two groups(P=0.008,0.026,0.026,respectively).On the receiver operating characteristic curve of these values,a 1.75 mg/dL ARF SCR value had 87.5%sensitivity and 84.8%specificity(P=0.011).CONCLUSION:Cessation or reduction of chemotherapy should be considered for patients who have an elevation of SCR levels during cisplatin combination chemotherapy.

Prolonged hyperthermic intraperitoneal chemotherapy duration with 90 minutes cisplatin might increase overall survival in gastric cancer patients with peritoneal metastases

BACKGROUND Advanced gastric cancer with synchronous peritoneal metastases(GC-PM)is associated with a poor prognosis.Although cytoreductive surgery with hyperthermic intraperitoneal chemotherapy(CRS-HIPEC)is a promising approach,only a limited number of Western studies exist.AIM To investigate the clinicopathological outcomes of patients who underwent CRSHIPEC for GC-PM.METHODS A retrospective analysis of patients with GC-PM was conducted.All patients were seen at the Department of General and Visceral Surgery,Hospital Barmherzige Brüder,Regensburg,Germany between January 2011 and July 2021 and underwent CRS-HIPEC.Preoperative laboratory results,the use of neoadjuvant trastuzumab,and the details of CRS-HIPEC,including peritoneal carcinomatosis index,completeness of cytoreduction,and surgical procedures were recorded.Disease-specific(DSS),and overall survival(OS)of patients were calculated.RESULTS A total of 73 patients were included in the study.Patients treated with neoadjuvant trastuzumab(n=5)showed longer DSS(P=0.0482).Higher white blood cell counts(DSS:P=0.0433)and carcinoembryonic antigen levels(OS and DSS:P<0.01),and lower hemoglobin(OS and DSS:P<0.05)and serum total protein(OS:P=0.0368)levels were associated with shorter survival.Longer HIPEC duration was associated with more advantageous median survival times[60-min(n=59):12.86 mo;90-min(n=14):27.30 mo],but without statistical difference.To obtain additional data from this observation,further separation of the study population was performed.First,propensity score-matched patient pairs(n=14 in each group)were created.Statistically different DSS was found between patient pairs(hazard ratio=0.2843;95%confidence interval:0.1119-0.7222;P=0.0082).Second,those patients who were treated with trastuzumab and/or had human epidermal growth factor receptor 2 positivity(median survival:12.68 mo vs 24.02 mo),or had to undergo the procedure before 2016(median survival:12.68 mo vs 27.30 mo;P=0.0493)were removed from the original study population.CONCLUSION Based on our experience,CRS-HIPEC is a safe and secure method to improve the survival of advanced GC-PM patients.Prolonged HIPEC duration may serve as a good therapy for these patients.

Randomized study of sinusoidal chronomodulated versus flat intermittent induction chemotherapy with cisplatin and 5-fluorouracil followed by traditional radiotherapy for locoregionally advanced nasopharyngeal carcinoma

Neoadjuvant chemotherapy plus radiotherapy is the most common treatment regimen for advanced nasopharyngeal carcinoma(NPC).Whether chronomodulated infusion of chemotherapy can reduce its toxicity is unclear.This study aimed to evaluate the toxic and therapeutic effects of sinusoidal chronomodulated infusion versus flat intermittent infusion of cisplatin(DDP)and 5-fluorouracil(5-FU)followed by radiotherapy in patients with locoregionally advanced NPC.Patients with biopsy-diagnosed untreated stages III and IV NPC(according to the 2002 UICC staging system)were randomized to undergo2 cycles of sinusoidal chronomodulated infusion(Arm A)or flat intermittent constant rate infusion(Arm B)of DDP and 5-FU followed by radical radiotherapy.Using a"MELODIE"multi-channel programmed pump,the patients were given 12-hour continuous infusions of DDP(20 mg/m2)and 5-FU(750 mg/m2)for 5days,repeated every 3 weeks for 2 cycles.DDP was administered from 10:00 am to 10:00 pm,and 5-FU was administered from 10:00 pm to 10:00 am each day.Chronomodulated infusion was performed in Arm A,with the peak deliveries of 5-FU at 4:00 am and DDP at 4:00 pm.The patients in Arm B underwent a constant rate of infusion.Radiotherapy was initiated in the fifth week,and both arms were treated with the same radiotherapy techniques and dose fractions.Between June 2004 and June 2006,125 patients were registered,and 124 were eligible for analysis of response and toxicity.The major toxicity observed during neoadjuvant chemotherapy was neutropenia.The incidence of acute toxicity was similar in both arms.During radiotherapy,the incidence of stomatitis was significantly lower in Arm A than in Arm B(38.1%vs.59.0%,P=0.020).No significant differences were observed for other toxicities.The 1-,3-,and 5-year overall survival rates were 88.9%,82.4%,and 74.8%for Arm A and 91.8%,90.2%,and 82.1%for Arm B.The 1-,3-,and 5-year progression-free survival rates were 91.7%,88.1%,and 85.2%for Arm A and 100%,94.5%,and 86.9%for Arm B.The 1-,3-,and 5-year distant metastasis-free survival rates were 82.5%,79.1%,and 79.1%for Arm A and 90.2%,85.2%,and 81.7%for Arm B.Chronochemotherapy significantly reduced stomatitis but was not superior to standard chemotherapy in terms of hematologic toxicities and therapeutic response.

Induction chemotherapy with docetaxel,cisplatin and fluorouracil followed by concurrent chemoradiotherapy for unresectable sinonasal undifferentiated carcinoma: Two cases of report

BACKGROUND Sinonasal undifferentiated carcinoma(SNUC) is a rare aggressive tumor that is often unresectable. Optimal treatment for patients with unresectable,locally advanced SNUC(LA-SNUC) has not been established,and the patient outcome remains poor. We report two cases of unresectable LA-SNUC in which induction chemotherapy with docetaxel,cisplatin and fluorouracil(TPF) followed by radiotherapy with concurrent cisplatin(CCRT),a standard treatment option for locally advanced head and neck cancer,demonstrated promising outcomes.CASE SUMMARY A 39-year-old man presented with tearing and pain in the right eye. A biopsy of the tumor invading the sinonasal cavities,right orbit and cranial base confirmed the diagnosis of LA-SNUC. Induction TPF chemotherapy induced remarkable tumor shrinkage and rapidly improved the symptoms. He subsequently received CCRT and achieved complete remission of the disease. The other case is a 21-year-old man who presented with worsening vision. The unresectable tumor involving the nasal septum and cranial base was pathologically diagnosed as SNUC. TPF chemotherapy followed by CCRT yielded complete remission of the disease with preserved visual function. Both patients have been disease-free for44 mo.CONCLUSION Induction TPF chemotherapy followed by CCRT may remarkably improve the outcomes in LA-SNUC patients.