Clinical efficacy of gemcitabine and cisplatin-based transcatheter arterial chemoembolization combined with radiotherapy in hilar cholangiocarcinoma

BACKGROUND Radical surgical resection is regarded as the best treatment for hepatic hilar cholangiocarcinoma. However, 60%-70% of patients have lost the chance of surgery at the time of diagnosis. Simple biliary stent or drainage tube placement may fail in a short time due to tumor invasion or overgrowth, bile accumulation, or biofilm formation. Effective palliative treatments to extend the effective drainage time are of great significance for improving the quality of life of patients and changing the prognosis of patients. AIM To investigate the clinical efficacy of gemcitabine and cisplatin-based transcatheter arterial chemoembolization (TACE) combined with radiotherapy in hilar cholangiocarcinoma.METHODS A retrospective analysis was conducted on patients clinically diagnosed with hilar cholangiocarcinoma from June 2014 to January 2017 at the Liaoning Provincial Cancer Hospital. Patients were evaluated by specialists, and those who were not suitable for surgery or unwilling to undergo surgery and met the inclusion criteria were included in the study. There were a total of 72 patients (34 males and 38 females) with an average age of 59.9 years (range, 40-72 years). According to percutaneous transhepatic biliary angiography and the patients’ wishes, stent implantation or biliary drainage tube implantation was used to relieve biliary obstruction. The patients were divided into either a control group or a combined treatment group according to their follow-up treatment. The control group consisted of a total of 35 patients who received simple biliary drainage tube placement and biliary stent implantation (7 patients with bilateral stents and 6 with a unilateral stent) and 22 patients receiving biliary drainage tube placement alone. The combined treatment group received TACE and extracorporeal radiotherapy after biliary drainage or biliary stent implantation and consisted of a total of 37 patients, including 21 patients receiving combined treatment after biliary stent placement (14 patients with bilateral stents and 7 with a unilateral stent) and 16 undergoing combined therapy after implanting the biliary drainage tube. In the combination treatment group, the TACE chemotherapy regimen employed gemcitabine and cisplatin, and the embolic agent was iodized oil. A particular dose was determined according to the patient's body surface area and the tumor staining indicated by DSA. In vitro radiotherapy was performed with intensity-modulated radiotherapy or threedimensional conformal radiotherapy at an average dose of 48.3 Gy. Both groups were followed from stent implantation or drainage tube implantation until the patient quitted or died. The median length of follow-up observation was 13 mo. The differences in overall survival time and the effect of different jaundice reducing methods (single stent, double stent, or biliary drainage) on the patency time and survival time of biliary stents were compared between the two groups;the related factors affecting overall survival time were analyzed. RESULTS The median survival time of the control group was 10.5 mo;the median survival time of patients with biliary stent implantation and those with percutaneous biliary drainage was 9.6 mo and 11.4 mo, respectively, and there was no statistically significant difference between them. The median survival time of the combined treatment group was 20.0 mo, which was significantly higher than that of the control group (P < 0.05). Among patients in the combined treatment group, the median survival time of patients who underwent biliary stent implantation and those who accepted percutaneous biliary drainage before the combination therapy was 19.5 mo and 20.1 mo, respectively, and there was no significant difference between them. In the combination treatment group, the mean time of median stent patency was 15.6 mo, which was significantly higher than that of the control group (7.0 mo;P < 0.05). The independent factors affecting survival time included age, whether to receive combination therapy, percutaneous biliary drainage tube implantation, and Bismuth-Corlette classification as type IV. CONCLUSION Gemcitabine and cisplatin-based TACE combined with radiotherapy can prolong the survival of patients with hilar cholangiocarcinoma. Independent predictors of survival include selection of combination therapy, Bismuth-Corlette classification as type IV, selection of percutaneous biliary drainage tube implantation, and age.

Improvement of Quality of Life with Shenfu Injection (参附注射液) in Non Small Cell Lung Cancer Patients Treated with Gemcitabine plus Cisplatin Regimen

Objective： To observe the effect of Shenfu injection （参附注射液, SFI） in treating non small cell lung cancer （NSCLC） patients on quality of life with gemcitabine （GEM） plus cisplatin （GP） regimen. Methods： Thirty-four patients were ready to receive GP regimen chemotherapy for treating NSCLC disease, according to lot-drawing, they were divided into SFI pre-treatment group （18 cases） and SFI post-treatment group （ 16 cases）. SFI pre-treatment group： During the first treatment course, chemotherapy was begun with SFI 60 ml, intravenous dripping on the 3rd day, once daily, consecutively for 10 days; on the 1st day, GP regimen （GEM 1250 mg/m^2 , intravenous dripping, on the 1st and 8th day; cisplatin 70 mg/m^2 on the 2nd day; 21 days as one cycle） was carried out; in the second treatment course GP regimen was merely given to serve as the self-control. SFI post-treatment group： the medicament sequence order was reversed from that of pre-treatment group. Using dual international quality of life （QOL） scores, the effect of SFI on the patients＂ QOL was observed through randomized self pre- and post- crossover control. Results： The QOL in the 34 patients after being treated by SFI in combination with GP chemotherapy regimen in one group, and GP chemotherapy regimen alone in the other, was improved in different degrees, with significant difference （P〈0.01）; comparision of SFI combined with GP chemotherapy regimen with GP chemotherapy alone showed that QOL in patients was significantly different （P〈0.01）. Conclusion： SFI could improve QOL in patients with NSCLC who were treated with GP regimen.

Experience with gemcitabine and cisplatin in the therapy of inoperable and metastatic cholangiocarcinoma

AIM： To study the activity of gemcitabine and cisplatin in a cohort of patients with inoperable or metastatic cholangiocarcinoma.METHODS： Chemotherapy-naive patients with pathologically proven cholangiocarcinoma, receiving treatment that consisted of gemcitabine at 1250 mg/m^2 in a 30-rain infusion on d 1 and 8, and cisplatin at 75 mg/m^2 at every 21-d cycle, were retrospectively analyzed.RESULTS： From .lune 2003 to December 2005, 42 patients were evaluated. Twelve patients （28%） had unresectable disease and 30 （72%） had metastatic disease. There were 28 males and 14 females with a median age of 51 years （range 33-67） and median ECOG PS of 1 （range 0-2）. A total of 171 cycles were given with a median number of cycles of 4 （range 1-6）. There were 0 CR, 9 PR, 11 SD and 13 PD （response rate 21%）. Grade 3-4 hematologic toxicities were： anemia in 33%, neutropenia in 22% and thrombocytopenia in 5%. Non-hematologic toxicity was generally mild. No cases of febrile neutropenia or treatment-related death were noted. The median survival was 10.8 mo （range 8.4-13 mo） and progression free survival was 8.5 mo. One-year survival rate was 40%.CONCLUSION： Our results indicate that the combination of gemcitabine and cisplatin had consistent efficacy in patients with unresectable or metastatic cholangiocarcinoma.

Feasibility and efficacy evaluation of metallic biliary stents eluting gemcitabine and cisplatin for extrahepatic cholangiocarcinoma

BACKGROUND Effective endoscopic management is fundamental for the treatment of extrahepatic cholangiocarcinoma(ECC).However,current biliary stents that are widely used in clinical practice showed no antitumor effect.Drug-eluting stents(DESs)may achieve a combination of local chemotherapy and biliary drainage to prolong stent patency and improve prognosis.AIM To develop novel DESs coated with gemcitabine(GEM)and cisplatin(CIS)-coloaded nanofilms that can maintain the continuous and long-term release of antitumor agents in the bile duct to inhibit tumor growth and reduce systemic toxicity.METHODS Stents coated with different drug-eluting components were prepared by the mixed electrospinning method,with poly-L-lactide-caprolactone(PLCL)as the drug-loaded nanofiber membrane and GEM and/or CIS as the antitumor agents.Four different DESs were manufactured with four drug-loading ratios(5%,10%,15%,and 20%),including bare-loaded(PLCL-0),single-drug-loaded(PLCL-GEM and PLCL-CIS),and dual-drug-loaded(PLCL-GC)stents.The drug release property,antitumor activity,and biocompatibility were evaluated in vitro and in vivo to confirm the feasibility and efficacy of this novel DES for ECC.RESULTS The in vitro drug release study showed the stable,continuous release of both GEM and CIS,which was sustained for over 30 d without an obvious initial burst,and a higher drug-loaded content induced a lower release rate.The drug-loading ratio of 10%was used for further experiments due to its ideal inhibitory efficiency and relatively low toxicity.All drug-loaded nanofilms effectively inhibited the growth of EGI-1 cells in vitro and the tumor xenografts of nude mice in vivo;in addition,the dual-loaded nanofilm(PLCL-GC)had a significantly better effect than the single-drug-loaded nanofilms(P<0.05).No significant differences in the serological analysis(P>0.05)or histopathological changes were observed between the single-loaded and drug-loaded nanofilms after stent placement in the normal porcine biliary tract.CONCLUSION This novel PLCL-GEM and CIS-eluting stent maintains continuous,stable drug release locally and inhibits tumor growth effectively in vitro and in vivo.It can also be used safely in normal porcine bile ducts.We anticipate that it might be considered an alternative strategy for the palliative therapy of ECC patients.

Systemic gemcitabine combined with intra-arterial low-dose cisplatin and 5-fluorouracil for advanced hepatocellular carcinoma: Seven cases

The combination of intra-arterial low-dose cisplatin and 5-fluorouracil (5-FU) is effective against advanced hepatocellular carcinoma (HCC). Systemic gemcitabine chemotherapy seems effective in many cancers. We report the results of combination therapy with systemic gemcitabine, intra-arterial low-dose cisplatin and 5-FU (GEMFP). Seven patients with non-resectable advanced HCC were treated with GEMFP. One course of chemotherapy consisted of daily intra-arterial cisplatin (20 mg/body weight/hour on d 1, 10 mg/body weight per 0.5 h on d 2-5 and 8-12), followed by 5-FU (250 mg/body weight per 5 h on d 1-5 and 8-12) via an injection port. Gemcitabine at 1000 mg/m2 was administered intravenously at 0.5 h on d 1 and 8. The objective response was 57%. The response to GEMFP was as follows: complete response (no patients), partial response (four patients), stable disease (three patients), and progressive disease (no patients). The median survival period was 8 mo (range, 5-55). With regard to the National Cancer Institute Common Toxicity Criteria (NCI-CTC) grade 3 or 4 adverse reactions, seven (100%), seven, six (86%) and one (14%) patients developed leukopenia, neutropenia, thrombocytopenia and anemia, respectively. GEMFP may potentially be effective for non- resectable advanced HCC, but it has severe hematologic toxicity.

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.

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.

Comparison of efficacy and toxicity between gemcitabine plus cisplatin and plus carboplatin in first-line treatment of advanced non-small cell lung cancer

Objective: To compare the efficacy and toxicity between gemcitabine plus cisplatin and plus carboplatin in first-line treatment of advanced non-small cell lung cancer (NSCLC). Methods: Gemcitabine 1000 mg/m2 iv, d1, 8; cisplatin 75 mg/m2 iv, d1, or 25 mg/m2 iv, d1-3; carboplatin AUC = 5 iv, d1; repeated every 21 days. Results: All 76 cases were available for objective response. Gemcitabine + cisplatin (GCis) group: among 33 cases, CR 1 case, PR 13 cases, MR 3 cases, SD 7 cases, PD 9 cases, response rate, disease control rate, time to progress (TTP), median survival time (MST) and 1-, 2-year survival rates were 42.42% (14/33), 72.73% (24/33), 5 months, 14 months and 66.67% (22/33), 12.12% (4/33), respectively; Gemcitabine + carboplatin (GCarb) group: among 43 cases, PR 13 cases, MR 11 cases, SD 7 cases, PD 12 cases, the results while comparing with those of GCis group were 30.23% (13/43), 72.09% (31/43), 4 months, 11 months and 48.84% (21/43), 2.33% (1/43), respectively. Among them, only MST between the two groups had significant statistic difference (χ2 = 2.45, P = 0.017). Mild to modest myelo-suppression as well as nausea and vomiting were observed. Conclusion: Both GCis and GCarb regimens had active and well-tolerated toxicity for advanced NSCLC. Cisplatin-based chemotherapy yields a substantial effective advantage over carboplatin-based regimens. Therefore, carboplatin and cisplatin are not equal-active and that cisplatin-based doublet regimens should remain the standard first-line therapy for patients with advanced NSCLC with good performance status.

Fixed Dose Rate versus Standard Dose Rate Infusion of Gemcitabine and Cisplatin in Advanced Stage Non-Small Cell Lung Cancer

Background: Comparing the efficacy and safety of gemcitabine at a fixed-dose rate (FDR) infusion (10 mg/m2/min) with the standard dose rate infusion in patients with locally advanced and metastatic non-small squamous cell carcinoma (NSCLC). Methods: The study randomized 60 patients with confirmed diagnosis of NSCLC to receive gemcitabine at a dose of 1000 mg/m2 on days 1 and 8 given as a 30-min infusion (Arm A) or at a rate of 10 mg/m2/min (Arm B). Cisplatin 75 mg/m2 was administered intravenously on day 2 in both arms. Results: No difference in overall response rate (46.6% versus 43.3%). Median time to progression for Arm A was 7 months (95% CI, 6.207 - 7.793 months), versus 6 months for Arm B (95% CI, 4.990 - 7.010 months). Median survival time was comparable [12 months (95% CI, 8.588 - 15.412 months) versus 11 months (95% CI, 9.066 - 12.934 months)] respectively. Two-year survival (18% versus 11%, p = 0.38) was detected. No treatment related deaths occurred. Main hematological toxicities were grade I and II neutropenia, in 36.7% and 53.3% respectively (p = 0.044). Grade III anemia was observed in 10% and 6.7% in both arms respectively (p = 0.024). Grade I and II nausea and vomiting was observed in 50% and 46.7%. Conclusions: FDR gemcitabine in combination with cisplatin had equivalent efficacy and more severe hematologic toxicities compared to the standard 30-min gemcitabine infusion with cisplatin in patients with advanced NSCLC.

Concurrent gemcitabine and cisplatin combined with 3D conformal radiotherapy for stage III non-small cell lung cancer

Objective： To study the toxicities and efficacy of concurrent gemcitabine plus cisplatin combined with three-dimensional conformal radiotherapy for stage Ⅲ non-small cell lung cancer （NSCLC）. Methods： Thirty-six patients with pathologically diagnosed NSCLC received radiotherapy and concurrent chemotherapy. There were 22 patients with stage Ilia and 14 patients with IIIb. Radiotherapy was given a total of 60-70 Gy in conventional fractionation. Chemotherapy included gemcitabine （600 mg/m^2） and cisplatin （20 mg/m^2）, once per week. Results： Thirty-two patients received a total dose of 60-72 Gy. Two patients received 56 Gy and another two patients received 58 Gy. Thirty-four patients received 4-6 weeks of chemotherapy, while two patients received only 2 weeks of chemotherapy. The overall response rate （CR ＋ PR）, complete response rate （CR）, partially response rate （PR） were 83.3% （30/36）, 11.1% （4/36） and 72.2% （26/36） respectively. The median follow-up duration was 18.4 months. The 1- and 2-year overall survival rates were 77.8% （28/36） and 55.6% （20/36）, respectively. Conclusion： Concurrent gemcitabine and cisplatin combined with three-dimensional conformal radiotherapy for stage III non-small cell lung cancer is effective and well tolerated. Lone-term results need further study.

Practical Use of Gemcitabine and Cisplatin Combination Therapy as First-Line Treatment for Japanese Patients with Advanced Biliary Tract Cancer

Gemcitabine and cisplatin combination therapy (GC) is accepted as a standard treatment for advanced biliary tract cancer (BTC). However, little information is available regarding such treatment in the clinical practice setting in Japan. We retrospectively examined the clinical data of patients with unresectable or recurrent BTC who received GC as first-line treatment. The regimen consisted of cisplatin (25 mg/m2) and gemcitabine (1000 mg/m2) administered intravenously on days 1 and 8 of repeated 3-week cycles. Twenty patients were analyzed. A total of 148 cycles of GC was administered, with a median of 8 and a range of 1 to 18 cycles. Treatment delay and dose reduction were noted in 35 (24%) and 41 (28%) of the 148 cycles, respectively. The major adverse events of grade 3 or 4 included neutropenia (50%), leukopenia (45%), anemia (30%), and thrombocytopenia (15%). Nonhematologic toxicities included nausea (10%), appetite loss (10%), and fatigue (10%). Median progression-free and overall survival times were 6.9 and 12.3 months, respectively. Gallbladder cancer showed a significantly higher response rate than did other types of BTC (chi-squaretest, P = 0.002). GC was thus effective and well tolerated as first-line chemotherapy for Japanese patients with advanced BTC in the clinical practice setting.

Role of gemcitabine and cisplatin as neoadjuvant chemotherapy in muscle invasive bladder cancer: Experience over the last decade

Objective:Neoadjuvant chemotherapy followed by radical cystectomy is considered the standard of care for patients with muscle invasive bladder cancer.In the last decade,interest in neoadjuvant chemotherapy has slowly shifted from methotrexate,vinblastine,doxorubicin and cisplatin regime to gemcitabine and cisplatin regime.There are many publications on gemcitabine and cisplatin regime in literature which cover different aspects of treatment.This review aims to summarise the findings published so far on gemcitabine and cisplatin regime and present it in a concise manner.Methods:A systematic literature review was conducted searching the PubMed
database in December 2016 using the medical subject heading(MeSH)with the terms gemcitabine,cisplatin,chemotherapy,muscle invasive bladder cancer,and neoadjuvant.All relevant studies were included and results were analysed.Results:A total of 13 studies were included which published between 2007 and 2015.These 13 studies comprised of 754 subjects suffering from muscle invasive bladder cancer.The proportion of male patients ranged from 60%to 86.4%and the median age ranged from 54.2 to 77.3 years in various studies.Complete pathological response(pT0)was seen in 30.0%of patients and pathological downstaging(<pT2)was seen in 48.67%of patients.Conclusion:As per latest guidelines,neoadjuvant chemotherapy is recommended for patients with muscle invasive bladder cancer.There is substantial pathological downstaging with low toxicity in patients of muscle invasive bladder cancer who receive neoadjuvant gemcitabine and cisplatin regime.

Assessment of maintenance oral Etoposide following induction chemotherapy with gemcitabine and cisplating in chemonaive extensive small cell lung cancer

Objective： The aim of our study was to evaluate the response and tolerability to treatment when using gemcitabine-cisplatin combination （GC）, followed by maintenance therapy of oral etoposide for non-progressive patients in trial to improve progression free survival and overall survival. Methods： Thirty nine patients with extensive small cell lung cancer （SCLC） and ECOG ≤ 2 received 4 cycles of chemotherapy consisting of gemcitabine 1000 mg/m^2 （day 1 and 8） cisplating 75 mgim2 （day 1） every three weeks. Twenty seven non-progressive patients after 4 cycles of chemotherapy were randomized either to receive oral etoposide 50 mg/m^2 for consecutive 15 days every 3 weeks vs no therapy for three months or progression. Results： Thirty nine eligible patients treated with GC, 27 non progressive patients were subsequently randomized to oral etoposide or observation. Median follow-up was 18 months. The overall response rate to GC was 59% and toxicity to oral etoposide was mild. There was improvement in median progression-free survival （PFS） favoring the maintenance arm of 10.5 months vs 7 months （P 〈 0.05）. Median overall survival （OS） had improved towards the maintenance arm （13 vs 11.5 months）. One year survival （60% vs 24%）, 18 months survival （20% vs 5%） favoring the maintenance. Multivariate analysis revealed that age, performance status, maintenance therapy, and response to treatment were independent prognostic factors for OS. Age, maintenance therapy, and response to treatment were highly significant factors for PFS. Conclusion： Gemcitabine-cisplatin is an effective and tolerable regiment for extensive disease of SCLC. The addition of 3 months of oral etoposide in non progressing patients was associated with a significant improvement of PFS and longer OS.

Clinical observation of docetaxel plus cisplatin versus gemcitabine plus cisplatin in the treatment of patients with advanced non-small-cell lung cancer

Objective： The aim of this study was to evaluate the clinical efficacy and side effects of docetaxel/cisplatin regiment and gemcitabine/cisplatin regiment in the patients with advanced non-small-cell lung cancer （NSCLC）. Methods： Seventy-six patients with advanced NSCLC who were chemotherapy-naive were enrolled in two groups. In docetaxel group （DP group） the patients received docataxel 75 mg/m^2 and cisplatin 60 mg/m^2 on day 1. In gemcitabine group （GP group） the patients received gemcitabine 1000 mg/m^2 on day 1 and day 8. The dosage of cisplatin was the same as DP group. The two regiments were administrated intravenously every 21 days as a cycle, each patient received 2-4 cycles. All patients were followed up until disease progressed or patients died. Results： The overall response rates were 43.5% in DP group and 45.9% in GP group. The response rate was significantly different between the initial treated group and retreated group in both two groups （53.8% vs 23.0% in DP group and 56% vs 25% in GP group, P 〈 0.05, respectively）. The main side effects were bone marrow suppression and thrombocytopenia. Conclusion： Docetaxel/cisplatin regiment and gemcitabine/cisplatin regiment for the patients with advanced NSCLC were efficient and well-tolerated chemotherapeutic approachs with low toxicity levels. The efficacy and major toxicity in two groups were similar.

Triplet chemotherapy with paclitaxel, gemcitabine, and cisplatin as second-line therapy for advanced urothelial carcinoma

Background: Methotrexate, vinblastine, doxorubicin, and cisplatin regimen, and gemcitabine and cisplatin regimen are widely used for advanced or metastatic urothelial carcinomas (UCs). However, a standard treatment for patients who fail these firstline chemotherapies is unavailable. We examined the efficacy and safety of secondline paclitaxel, gemcitabine, and cisplatin (PCG) chemotherapy in Japanese patients. Methods: Between 2004 and 2010, 25 patients with metastatic UCs who failed to respond to platinumbased regimens were treated with PCG. They received intravenous paclitaxel (60 mg/m2) and gemcitabine (1000 mg/m2) on days 1 and 8, and cisplatin (70 mg/m2) on day 2 of every 21 day course. We retrospectively collected patients’ clinical and pathological data and evaluated adverse effects and survivals. Results: Patients underwent 95 PCG cycles in all (average, 3.8 cycles per patient). One patient (4%) achieved complete response, 5 (20%) showed partial response, 8 (42%) had disease stabilization, and 5 (26%) had disease progression. Median overall survival was 8.5 months. Neutropenia and thrombocytopenia of grade ≥ 3 were observed in 68% and 56% of patients, respectively. No treatment related death occurred. Multivariate analysis revealed that hemoglobin levels 1.73 m2) were significant risk factors for overall survival. Conclusion: PCG chemotherapy in the secondline setting potentially contributed to good prognosis in selected patients with relatively significant but tolerable toxicity.

Clinical analysis of preoperative induction chemotherapy with gemcitabine combined with cisplatin for locally advanced non-small cell lung cancer

Objective:The purpose of this study was to assess the curative effect and adverse reaction of preoperative induction chemotherapy with gemcitabine combined with cisplatin for locally advanced non-small cell lung cancer(NSCLC).Methods:This prospective randomized controlled trial included 115 patients with locally advanced NSCLC were randomly divided into experimental and control groups and were treated from January 2007 to January 2010.The experimental group of 63 cases was treated with two cycles of induction chemotherapy before operation,radical surgery had been performed about three weeks after completion of chemotherapy,followed by received two cycles of chemotherapy.And the control group(52 cases) was treated at first with radical surgery,then treated with four cycles of chemotherapy.Two groups of the cases received routine thoracic radiotherapy with a total dose of 45 Gy.One cycle of gemcitabine combined with cisplatin regimen included gemcitabine 1000 mg/m2 on day 1 and day 8 and cisplatin 25 mg/m2 on day 1,day 2 and day 3 by intravenous infusion,with 21 days as one cycle.The tumor recurrence was evaluated by chest CT and abdominal B-ultrasound.Efficacy and toxicity results were compared by two groups.Results:All patients were followed up for three months to two years.The surgical stage of the experimental group reduced,two-years disease-free survival and postoperative recovery in the experimental group were better than in the control group,the difference was statistical significant.Toxicity and side effect after chemotherapy were mainly bone marrow suppression and gastrointestinal reactions,other complications included thrombocytopenia,leukopenia,anemia,liver and kidney dysfunction were no significant difference in two groups.Conclusion:Preoperative induction chemotherapy with gemcitabine combined with cisplatin for locally advanced lung cancer can reduce the surgical staging and extend the postoperative disease-free survival.

Effects of gemcitabine and cisplatin chemotherapy in advanced non-small cell lung cancer patients with RRM1 low protein expression

Objective： The aim of this study was to observe the efficacy of gemcitabine combined with cisplatin （GP） in advanced non-smaU cell lung cancer （NSCLC） patients with low expression of ribonucleotide reductase 1 （RRM1） protein using immunohistochemistry. Methods： RRM1 protein expression in tumor tissue was detected by streptavidin-peroxidase （SP） method of immunohistochemistry. GP regimen （gemcitabine 1000-1250 mg d1, d8, cisplatin 75 mg/m2） was given to advanced NSCLC patients with low expression of RRM1 protein. Results： In the total of 40 patients, these patients with RRM1 low expression performing GP chemotherapy had a good response rate, the objective response rate （ORR） was 47.5% （95% CI, 32.02%- 62.98%）, and the disease control rate （DCR） was 72.5% （95 % CI, 65.44%-79.56%）. ORR is 45.45% （5/11） in the squamous cell carcinoma patients while 48.15% （13/27） in the adenocarcinoma patients. Conclusion： Supedor ORR and DCR were found in advanced NSCLC patients with low expression of RRM1 protein expression performing GP regimen.

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.

Gemcitabine combined with cisplatin in the treatment of advanced malignant pleural mesothelioma (MPM): Institutional experience

Objective： The aim of our study was to evaluate the efficacy and safety of gemcitabine and cisplatin in patients with previously untreated advanced malignant pleural mesothelioma （MPM）. Methods： Thirty-three eligible patients with histologically proven advanced MPM with ECOG PS of 〈 2 and had adequate liver and kidney functions received gemcitabine （1000 mg/m2） on days 1 and 8 combined with cisplatin （80 mg/m^2） on day 1. Results： The majority of the study group were males and constituted 87.9% （n = 29）, while females constituted 12.1% （n = 4）. The median age was 52 years and ranged from 37 to 69 years. Regarding SWOG performance status, 5 patients were PS 0, 21 patients were PS 1 and 7 patients were PS 2. Regarding pathological subtypes, epithelial histology represented 84.8% of the study （n = 28） while sarcomatoid type represented 6% （n = 2） and biphasic type accounted for 9% （n = 3）. Regarding staging according to IMIG staging system, 12.1% of patients were stage Ⅱ, 54.5% were stage Ⅲand 33.3% were stage Ⅳ. Only one patient （3%） had attained a complete response, 18 patients （54.5%） showed partial response, 12 patients （36.4%） showed stationary disease, while 2 patients （6.1%） showed progressive disease. The correlation between response rate obtained and PS was statistically significant （P = 0.029）. After a median follow-up of 14.4 months, the median survival time was 20.3 months （95% Cl： 14.58-26.01 months） and the progression free survival time was 11.8 months （95% CI： 10.76-12.83 months） Conclusion： The combination of gemcitabine and cisplatin is an active and safe treatment in patients with MPM. Further larger comparative studies are warranted to document this finding.

Human bone marrow mesenchymal stem cell-derived exosomes loaded with gemcitabine inhibit pancreatic cancer cell proliferation by enhancing apoptosis

BACKGROUND Pancreatic cancer remains one of the most lethal malignancies,and has limited effective treatment.Gemcitabine(GEM),a chemotherapeutic agent,is commonly used for clinical treatment of pancreatic cancer,but it has characteristics of low drug delivery efficiency and significant side effects.The study tested the hypothesis that human bone marrow mesenchymal stem cell(MSC)-derived exosomes loaded with GEM(Exo-GEM)would have a higher cytotoxicity against human pancreatic cancer cells by enhancing their apoptosis.AIM To investigate the cytotoxicity of MSC-derived Exo-GEM against pancreatic cancer cells in vitro.METHODS Exosomes were isolated from MSCs and characterized by transmission electron microscopy and nanoparticle tracking analysis.Exo-GEM through electroporation,sonication,or incubation,and the loading efficiency was evaluated.The cytotoxicity of Exo-GEM or GEM alone against human pancreatic cancer Panc-1 and MiaPaca-2 cells was assessed by MTT and flow cytometry assays.RESULTS The isolated exosomes had an average size of 76.7 nm.The encapsulation efficacy and loading efficiency of GEM by electroporation and sonication were similar and significantly better than incubation.The cytotoxicity of Exo-GEM against pancreatic cancer cells was stronger than free GEM and treatment with 0.02μM Exo-GEM significantly reduced the viability of both Panc-1 and MiaPaca-2 cells.Moreover,Exo-GEM enhanced the frequency of GEMinduced apoptosis in both cell lines.CONCLUSION Human bone marrow MSC-derived Exo-GEM have a potent cytotoxicity against human pancreatic cancer cells by enhancing their apoptosis,offering a promising drug delivery system for improving therapeutic outcomes.