Gemcitabine Plus Cisplatin Chemotherapy Research Articles

Cachexia Index Is a Prognostic Indicator in Patients With Metastatic Urothelial Carcinoma Treated With Systemic Chemotherapy.

Cancer cachexia is associated with poor prognosis in patients with metastatic urothelial carcinoma (mUC). The objective of the study was to assess the cachexia index (CXI), which is a new indicator assessing the status of cancer cachexia, as a prognostic indicator for mUC patients treated with gemcitabine plus cisplatin (GC) chemotherapy. The study included 55 patients with mUC who underwent GC chemotherapy between 2008 and 2022 as first-line chemotherapy. The CXI at the start of chemotherapy was determined as follows: CXI=(serum albumin × skeletal muscle mass index)/ (neutrophil count/lymphocyte count). Patients were categorized into two groups based on a median CXI value (CXI-high and CXI low). We used Kaplan-Meier curves and multivariate Cox proportional hazards regression models to assess the association between the CXI and overall survival (OS). At the start of GC chemotherapy, significant differences were not found in patients' characteristics. The median OS was significantly shorter in the CXI-low group [10.0 months (95% confidence interval (CI)=5.1-12.8)] than in the CXI-high group [22.3 months (95% CI=13.6-NA), p<0.05]. Multivariate analysis revealed that low CXI was a predictor of a poor prognosis [hazard ratio (HR)=2.25, 95% CI=1.12-4.52, p<0.05]. CXI might be useful as a prognostic indicator for patients with mUC undergoing first-line GC chemotherapy.

Cost-effectiveness of camrelizumab combined with chemotherapy in the first-line treatment of recurrent or metastatic nasopharyngeal carcinoma in China

ObjectiveThis study aimed to investigate the cost-effectiveness of adding Chinese-developed anti-PD-1 antibody camrelizumab to first-line platinum-doublet chemotherapy in patients with recurrent or metastatic nasopharyngeal carcinoma (L/M NPC) from the perspective...

Predicting response of gemcitabine plus cisplatin chemotherapy using RNA sequencing in patients with advanced urothelial carcinoma.

66 Background: Despite of advancement using new agents including ICIs in treatment of urothelial carcinoma (UC), cisplatin-based chemotherapy is still standard of care in both 1st line palliative setting and perioperative setting. Previous studies regarding response prediction of cisplatin-based chemotherapy are limited in selecting target molecule or gene, there have been no comprehensive study for whole genome information. This study aimed to identify key genes to predict response of gemcitabine plus cisplatin (GC) in advanced UC by mRNA sequencing (RNA-seq). Methods: Between JAN 2016 and DEC 2019, advanced UC patients treated with GC and underwent response evaluation were enrolled. Patients were divided into the responder group (CR or PR) and non-responder group (SD or PD). RNA was extracted from the formalin fixed embedded tissue (FFED) and RNA-seq was performed on the Illumina RNA-seq platform. Differentially expressed genes (DEGs) were identified between responder group and non-responder group. Marker selection was performed as following steps: (1) DESeq2 (Adjusted P-value &lt; 0.1) and Mann-Whitney U test (P-value &lt; 0.05), (2) random forest (RF) and logistic regression, and (3) assessments for relevant markers by analyzing RNA/Protein expression level, survival information, and antibody staining results using ProteinAtlas. Results: Twenty-nine patients received GC chemotherapy during study period. Among them, 10 patients who had available FFED specimens and clear response evaluation were enrolled and performed RNA-seq. Median age was 65.5 years (range, 62-76), and all were male. They were grouped of 7 patients in responder and 3 patients in non-responder. Among 13,773 genes based on RNAseq, we identified 37 DEGs candidate (Step 1), followed by 22 DEGs selected (Step 2), and finally 9 DEGs were identified (Step 3). Among the 9 DEGs, 3 genes (UPK2, PCGF3, and POFUT1) were consistently expressed with survival data of TCGA, the expression of 3 (ITGA3, HSPA1B, GSTM3) was the opposite of that of TCGA, and the remaining 3 genes (S100A2, TDRP, and RPS6KA2) were not relevant. Conclusions: We found 3 key genes (UPK2, PCGF3, and POFUT1) that related with favorable response of GC in our advanced UC cohort which were confirmed in TCGA data. Our study results should be further investigated in an expansion cohort using immunohistochemistry staining matched with key genes for convenient practical application.

The tumor immune microenvironment of nasopharyngeal carcinoma after gemcitabine plus cisplatin treatment.

Gemcitabine plus cisplatin (GP) chemotherapy is the standard of care for nasopharyngeal carcinoma (NPC). However, the mechanisms underpinning its clinical activity are unclear. Here, using single-cell RNA sequencing and T cell and B cell receptor sequencing of matched, treatment-naive and post-GP chemotherapy NPC samples (n = 15 pairs), we show that GP chemotherapy activated an innate-like B cell (ILB)-dominant antitumor immune response. DNA fragments induced by chemotherapy activated the STING type-I-interferon-dependent pathway to increase major histocompatibility complex class I expression in cancer cells, and simultaneously induced ILB via Toll-like receptor 9 signaling. ILB further expanded follicular helper and helper type 1 T cells via the ICOSL-ICOS axis and subsequently enhanced cytotoxic T cells in tertiary lymphoid organ-like structures after chemotherapy that were deficient for germinal centers. ILB frequency was positively associated with overall and disease-free survival in a phase 3 trial of patients with NPC receiving GP chemotherapy ( NCT01872962 , n = 139). It also served as a predictor for favorable outcomes in patients with NPC treated with GP and immunotherapy combined treatment (n = 380). Collectively, our study provides a high-resolution map of the tumor immune microenvironment after GP chemotherapy and uncovers a role for B cell-centered antitumor immunity. We also identify and validate ILB as a potential biomarker for GP-based treatment in NPC, which could improve patient management.

Phase 1b clinical trial of pucotenlimab (HX008), a novel anti-PD-1 monoclonal antibody, combined with gemcitabine and cisplatin in the first-line treatment of metastatic triple-negative breast cancer.

BackgroundPucotenlimab, also called HX008, is a humanized anti-PD-1 antagonist IgG4 mAb. It blocks programmed cell death protein 1 (PD-1), programmed-death ligand 1 (PD-L1), and programmed death ligand-2 (PD-L2). In the CBCSG 006 trial, gemcitabine plus cisplatin (GP) has shown impressive antitumor activity as first-line therapy for metastatic triple-negative breast cancer (mTNBC). The phase 1b study was conducted to assess the safety and preliminary antitumor activity of pucotenlimab when combined with GP in patients with mTNBC in the first-line setting.MethodsEligible patients with mTNBC with ≥6 months of DFI (disease-free interval) who have never received antitumor therapy for metastatic disease were screened. Participants received pucotenlimab at 3 mg/kg (d1, q3w) plus gemcitabine at 1,250 mg/m2 (d1, 8, q3w) and cisplatin at 75 mg/m2 (d1, q3w). Eligible patients received up to six cycles of pucotenlimab along with GP chemotherapy, while pucotenlimab could be maintained until disease progression or unacceptable toxicity occurred or withdrawal of informed consent. This study was registered in China under registration number CTR20191353.ResultsBetween July 2019 and March 2020, 31 patients were enrolled in this study. The median age was 50 (range 28–68) years. Among 31 patients who were evaluated, 25 (80.6%) experienced objective response and the other six (19.4%) experienced stable disease (SD). As of 4 August, the median progression-free survival (PFS) was 9.0 months (95% CI, 6.2–9.2). The most common grade 3 or 4 treatment-related adverse events included neutropenia (74.1%), anemia (35.5%), thrombocytopenia (32.3%), hypocalcemia (9.7%), hypokalemia (9.7%), and alanine aminotransferase increased (6.5%). There were no treatment-related deaths.ConclusionPucotenlimab plus GP demonstrated promising activity and a manageable safety profile in patients with mTNBC in the first-line setting.

Response to Pembrolizumab After Dose-Reduced Cisplatin Plus Gemcitabine Chemotherapy Is Inferior to That After Carboplatin Plus Gemcitabine Chemotherapy in Cisplatin-Unfit Patients With Advanced Urothelial Carcinoma.

Response to pembrolizumab after first-line chemotherapy is vital to prolonged survival in advanced, unresectable, and/or metastatic urothelial carcinoma (aUC). However, there are sparse clinical data on host-tumor immune modification by first-line platinum-based chemotherapy. This study investigated the association between response to first-line gemcitabine plus cisplatin (GC) or carboplatin (GCarbo) chemotherapy and response to subsequent pembrolizumab treatment. A multicenter-derived database registered 454 patients diagnosed with aUC between 2008 and 2020. Of these, 108 patients who received first-line GC or GCarbo followed by second-line or later pembrolizumab were eligible for investigation and were classified into 3 groups: 48 receiving full-dose GC, 21 receiving dose-reduced GC, and 39 receiving GCarbo. Overall survival (OS) was calculated using the Kaplan-Meier method and compared using the log-rank test. Possible factors associated with the response to pembrolizumab were evaluated using binary logistic regression methods. The rate of patients undergoing surgical removal of the primary organ was higher and creatinine clearance was lower in the dose-reduced GC and GCarbo groups than in the full-dose GC groups. Pembrolizumab responders had significantly better survival benefits than nonresponders. The rate of pembrolizumab responders was much higher in first-line chemotherapy responders than in first-line chemotherapy nonresponders. In contrast to the full-dose GC and GCarbo groups, the pembrolizumab responder rate was lower, and no association was observed between response to first-line chemotherapy and response to pembrolizumab in the dose-reduced GC group. Cisplatin and carboplatin may play an important role in the antitumor immune response, which could impact the outcome of subsequent pembrolizumab treatment. Given that the rate of response to pembrolizumab after dose-reduced GC chemotherapy was relatively low, this regimen is not recommended for cis-unfit patients with aUC. Further studies are required to understand the mechanisms responsible for the cross-reactivity of platinum and immune checkpoint inhibitors.

RRM1 Expression as a Prognostic Biomarker for Unresectable or Recurrent Biliary Tract Cancer Treated with Gemcitabine plus Cisplatin.

The combination of gemcitabine plus cisplatin (GP) is regarded as a first-line treatment for patients with unresectable or recurrent biliary tract cancer (BTC). Several proteins including human equilibrative nucleoside transporter-1 (hENT1), deoxycytidine kinase (DCK), cytidine deaminase (CDA), and ribonucleotide reductase subunit 1 (RRM1) are known to be involved in gemcitabine uptake and metabolism. This study was aimed to identify the predictive and prognostic values of these biomarkers in patients who treated with GP for advanced BTC. Tumor samples were obtained from 34 patients with unresectable or recurrent BTC who were treated with GP between August 2015 and February 2018. Intratumoral expression of hENT1, DCK, CDA and RRM1 was determined by immunohistochemistry and analyzed for association with chemotherapy response, progression-free survival (PFS) and overall survival (OS). Median OS was significantly longer in the RRM1-negative group than in the RRM1-positive (9.9 months vs. 5.9 months, p = 0.037). Multivariate adjustment analyses also demonstrated RRM1 expression as an independent prognostic factor for OS in patients treated with GP chemotherapy. Increased intratumoral expression of RRM1 on immunohistochemical staining may be a biomarker predicting poor survival in patients with GP chemotherapy for advanced BTC. Large-scale well-predefined prospective research is needed to validate the utility of biomarkers in clinical practice.

Abstract PS12-11: Phase 1b clinical trial of HX008, a novel anti-PD-1 monoclonal antibody, Combined with gemcitabine and cisplatin in the first-line treatment of metastatic triple-negative breast cancer

Abstract Background HX008 is a humanized IgG4S228P anti-PD-1 monoclonal antibody with an engineered Fc domain. Gemcitabine plus cisplatin (GP) has shown satisfying antitumor activity as first-line therapy for metastatic triple-negative breast cancer (mTNBC) in CBCSG 006 trial (ClinicalTrials.gov, NCT01287624). The phase 1b study was conducted to assess the safety and preliminary antitumor activity of HX008, combined with GP in patients with mTNBC in first-line setting. Methods Eligible patients are mTNBC with ≥6 months DFI who never receive antitumor therapy for metastatic disease. Participants received HX008 at 3mg/kg (d1, q3w) plus gemcitabine at 1250mg/m2 (d1, 8, q3w) and cisplatin 75mg/m2 (d1, q3w). At most 6 cycles of GP chemotherapy were given, while HX 008 could be maintained until disease progression or unacceptable toxicity occurred. Results Between July 2019 and March 2020, a total of 31 patients were enrolled in this study. Median (range) age was 50 (29-69) years. Among 31 patients who were evaluated, 25 (80.6%) experienced objective response and the other 6 (19.4%) experienced stable disease (SD). The median progression free survival (PFS) was 9.07 months (95%CI,7.29m-13.01m). The PFS data was not yet mature, for nearly half of the intent-to-treat population has not progressed by October 9, 2020. The most common treatment-related adverse events of grade 3 or 4 included neutropenia (71.0%), anemia (55.5%), thrombocytopenia (32.3%), hypocalcemia (9.68%), hypokalemia (6.45%), and Alanine aminotransferase increased (6.45%). There were no treatment-related deaths. Conclusion HX008 plus GP demonstrated promising activity and manageable safety in patients with mTNBC in first-line setting. Clinical trial information: CHINADRUGTRIALS.ORG, CTR 20191353. Citation Format: Xichun Hu, Jun Cao, Biyun Wang, Jian Zhang, Leiping Wang, Zhonghua Tao, Ting Li. Phase 1b clinical trial of HX008, a novel anti-PD-1 monoclonal antibody, Combined with gemcitabine and cisplatin in the first-line treatment of metastatic triple-negative breast cancer [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PS12-11.

High platelet-to-lymphocyte ratio is associated with poor prognosis in patients with unresectable intrahepatic cholangiocarcinoma receiving gemcitabine plus cisplatin

BackgroundSeveral systemic inflammatory response (SIR) markers, including platelet-to-lymphocyte ratio (PLR), neutrophil-to-lymphocyte ratio (NLR), lymphocyte-to-monocyte ratio (LMR), and albumin-to-globulin ratio (AGR), have emerged as prognostic markers in various cancers. The aim of this study was to explore the impact of SIR markers on the survival outcomes of unresectable intrahepatic cholangiocarcinoma (IHC) patients.MethodsPatients with histologically confirmed, unresectable IHC treated with gemcitabine plus cisplatin (GP) chemotherapy in a single tertiary hospital from 2012 to 2016 were retrospectively reviewed. Progression-free survival (PFS) and overall survival (OS) were determined using unadjusted Kaplan-Meier and adjusted Cox-proportional-hazards analysis. Time-dependent receiver operating characteristic (ROC) analysis was performed to compare the performance of the SIR markers in predicting OS.ResultsA total of 137 patients received a median of six cycles (interquartile range [IQR], 3–11) of GP chemotherapy with a median observation time of 9.9 months (range, 1.8–54.7 months). The median PFS and OS of all patients were 7.8 months and 9.9 months, respectively. Among the SIR markers, high PLR (> 148) and high NLR (> 5) were associated with a short PFS (Hazard ratio [HR] 1.828, P = 0.006; HR 1.738, P = 0.030, respectively) and short OS (HR 2.332, P < 0.001; HR 2.273, P < 0.001, respectively). Low LMR (< 3.5) and low AGR (< 1.2) were associated with a short OS (HR 2.423, P < 0.001; HR 1.768, P = 0.002, respectively). In multivariable cox-regression analysis, high PLR (HR 1.766, P = 0.009) and distant lymph node (LN) metastasis (HR 2.085, P = 0.001) were associated with a short PFS. High PLR (HR 1.856, P = 0.002) was an independent predictor of a short OS, along with distant LN metastasis (HR 1.929; P < 0.001), low LMR (HR 1.691; P = 0.041), and low level of serum albumin (< 3.5 g/dL) (HR 1.632; P = 0.043). Time-dependent ROC analysis revealed that the area under the curve of PLR for predicting overall survival was greater than that of NLR, LMR, and AGR at most time points.ConclusionsHigh PLR was an independent prognostic factor of a short PFS and OS in patients with unresectable IHC receiving GP chemotherapy.

Gemcitabine Plus Cisplatin Chemotherapy Prolongs the Survival in Advanced Hilar Cholangiocarcinoma: A Large Multicenter Study.

Gemcitabine plus cisplatin (GC) is recommended as first-line treatment for advanced cholangiocarcinoma. We investigated the impact of GC in patients with unresectable hilar cholangiocarcinoma (HC) based on the time taken for effective biliary drainage (EBD). We retrospectively enrolled 113 patients with unresectable HC. Thirty-nine and 74 patients received GC chemotherapy and best supportive care (BSC), respectively. EBD was defined as a reduction in total bilirubin >50% or to a value <2 mg/dL after the drainage procedure. Early EBD (eEBD) and delayed EBD (dEBD) were separated by 2 weeks. Overall survival (OS) was estimated. The GC group showed a significantly longer median OS than the BSC group (12.8 vs. 6.1 mo; P<0.001). Moreover, the eEBD group experienced a significantly longer OS than the dEBD group (8.2 vs. 4.3 mo; P<0.001). GC led to improved OS in the eEBD (12.8 vs. 6.8 mo; P=0.003) and dEBD (12.2 vs. 3.4 mo; P=0.009) groups. In multivariate analysis, dEBD (adjusted hazard ratio [aHR], 1.785; 95% confidence interval [CI], 1.183-2.691; P=0.006), BSC (aHR, 2.409; 95% CI, 1.579-3.675; P<0.001), and an ECOG status ≥2 (aHR, 3.721; 95% CI, 2.093-6.615; P<0.001) were associated with poor prognosis. In GC group, the older (70 y and above) patients did not have a higher risk of death than younger patients. GC prolongs the survival of patients with unresectable HC, even those with dEBD or elderly.

Impact on gemcitabine plus cisplatin in unresectable hilar cholangiocarcinoma patients according to effective biliary drainage: A multicenter study.

e15658 Background: Hilar cholangiocarcinoma (HC) is known to have a poor prognosis due to cholangitis and lack of effective chemotherapeutic regimen. Since 2010, gemcitabine plus cisplatin (GP) is recommended as first-line chemotherapy in cholangiocarcinoma. However, it is still unclear whether GP is effective on HC. We aimed to evaluate the impact on GP in unresectable HC patients according to effective biliary drainage (EBD). Methods: From 2010 to 2016, 112 patients with unresectable HC confirmed by biopsy at three tertiary referral hospitals in Korea were enrolled. 38 patients received GP [cisplatin (25 mg per square meter of body-surface area) followed by gemcitabine (1000 mg per square meter), each administered on days 1 and 8, every 3 weeks]. 74 patients received best supportive care (BSC). The EBD group was defined as a total bilirubin decrease of less than 2 mg/dl within 2 weeks after the first drainage procedure or 50% reduction than pre-procedure total bilirubin. Overall survival (OS) was evaluated in GP group and BSC group according to EBD achieved using the Kaplan–Meier survival curve and the log-rank test. Results: When compared with the BSC group (n = 74), the GP group (n = 38) obtained a benefit in OS (median OS, 6.14 vs 12.7 months, p &lt; 0.001). Moreover, patients with EBD experienced significantly longer OS compared with ineffective biliary drainage (IEBD) patients (median OS, 8.03 vs 5.01 months, p &lt; 0.005). GP chemotherapy was beneficial for OS in IEBD group (p &lt; 0.001) as well as in EBD group (p &lt; 0.005). In the multivariate analysis, GP chemotherapy (HR 0.33, 95% CI 0.21–0.52, p &lt; 0.001), EBD (HR 0.60, 95% CI 0.40–0.91, p &lt; 0.001) and 2 more metastatic site (HR 3.21, 95% CI 1.66–6.18, p &lt; 0.001) were significant prognostic factors. Conclusions: GP chemotherapy provides longer survival in HC, regardless of effective or ineffective biliary drainage.

Clinical efficacy and mechanism of Pralatrexate combined with Palbociclib Isethionate in treatment of bladder cancer patients.

The clinical efficacy and mechanism of Pralatrexate (PTX) combined with Palbociclib Isethionate (PAL) in the treatment of bladder cancer patients was investigated. A retrospective analysis of medical records of 82 bladder cancer patients admitted to Shengjing Hospital of China Medical University from February 2015 to February 2018 was performed. Patients treated with PTX combined with PAL served as study group (42 cases) and patients with conventional GC (gemcitabine plus cisplatin) chemotherapy regimen were the control group (40 cases). Changes in liver function indexes before and after treatment were observed, including alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), and total bilirubin (TBil). RT-qPCR was used for detection of relative expression levels of serum dihydrofolate reductase (DHFR) and vascular endothelial growth factor (VEGF) before and after treatment in the two groups. The clinical efficacy after treatment and adverse reactions during treatment were observed in the two groups. There was no significant difference in the clinical remission rate (RR) nor in the serum ALT, AST, ALP and TBil levels between the study and the control groups (P>0.05). Concentrations of serum ALT, AST, ALP and TBil were significantly higher than those before treatment in both groups (P<0.05). Serum ALT, AST, ALP and TBil concentrations in study group were significantly lower than those in control group (P<0.05). There was no significant difference in the incidence of thrombocytopenia and leukopenia between the two groups (P>0.05). There was no significant difference in relative expression levels of serum DHFR mRNA and VEGF mRNA before treatment between the study and control groups (P>0.05). Those after treatment were significantly lower than those before treatment in both groups (P<0.05), and those after treatment in study group were significantly lower than those in control group (P<0.05). PTX combined with PAL can reduce adverse reactions of nausea and vomiting and liver function impairment during treatment and suppress tumor neovascularization. This is achieved possibly by inhibiting expression levels of DHFR and VEGF, thereby killing cancer cells. PTX combined with PAL may become a new method for the treatment of bladder cancer patients. DHFR and VEGF are expected to become novel therapeutic targets for the treatment of bladder cancer.

The impact of a solitary kidney on tolerability to gemcitabine plus cisplatin chemotherapy in urothelial carcinoma patients: a retrospective study

There is little information on tolerability to cisplatin-based chemotherapies in patients with a solitary kidney after nephroureterectomy. We evaluated the impact of having a solitary kidney on tolerability to gemcitabine plus cisplatin (GC) chemotherapy in urothelial carcinoma patients. We retrospectively reviewed medical records of patients treated between August 2007 and November 2015. Eligible patients had received GC as first-line chemotherapy, including as neoadjuvant and adjuvant treatment. Patients who commenced GC chemotherapy after nephroureterectomy comprised the solitary kidney (SK) group; the remaining patients (i.e., those with both kidneys) comprised the BK group. Incidences of hematologic toxicities and renal insufficiency were examined and compared between two groups. There were 16 patients in the SK group and 31 in the BK group. The incidence of hematologic toxicity (grade 3/4) was not significantly different between the two groups (neutropenia: 68.8 vs. 74.2%, respectively (P = 0.959); thrombocytopenia: 31.2 vs. 51.6%, respectively (P = 0.307); and anemia: 12.5 vs. 38.7%, respectively (P = 0.094)). Multivariate analysis revealed no statistically significant association between having a SK and severe hematologic toxicities. Moreover, no significant differences were observed in the incidence of acute kidney injury. The mean differences in serum creatinine and estimated glomerular filtration rate between baseline and each post-chemotherapy cycle were similar when comparing the SK and BK groups. There is no evidence that tolerability to GC chemotherapy is inferior in patients with a solitary kidney. Therefore, there may be no need to avoid administering CDDP-based chemotherapy to such patients.

MP27-06 DEVELOPMENT OF A NEW PROGNOSTIC MODEL TO PREDICT SURVIVAL OF PATIENTS WITH METASTATIC UROTHELIAL CARCINOMA RECEIVING FIRST-LINE GEMCITABINE PLUS CISPLATIN CHEMOTHERAPY: MULTICENTER RETROSPECTIVE STUDY BY THE SAPPORO MEDICAL UNIVERSITY UROLOGIC ONCOLOGY CONSORTIUM (SUOC)

You have accessJournal of UrologyBladder Cancer: Upper Tract Transitional Cell Carcinoma II1 Apr 2016MP27-06 DEVELOPMENT OF A NEW PROGNOSTIC MODEL TO PREDICT SURVIVAL OF PATIENTS WITH METASTATIC UROTHELIAL CARCINOMA RECEIVING FIRST-LINE GEMCITABINE PLUS CISPLATIN CHEMOTHERAPY: MULTICENTER RETROSPECTIVE STUDY BY THE SAPPORO MEDICAL UNIVERSITY UROLOGIC ONCOLOGY CONSORTIUM (SUOC) Takeshi Maehana, Toshiaki Tanaka, Tetsuya Shindo, Atsushi Takahashi, Naoki Ito, Keisuke Taguchi, Hiroshi Hotta, and Naoya Masumori Takeshi MaehanaTakeshi Maehana More articles by this author , Toshiaki TanakaToshiaki Tanaka More articles by this author , Tetsuya ShindoTetsuya Shindo More articles by this author , Atsushi TakahashiAtsushi Takahashi More articles by this author , Naoki ItoNaoki Ito More articles by this author , Keisuke TaguchiKeisuke Taguchi More articles by this author , Hiroshi HottaHiroshi Hotta More articles by this author , and Naoya MasumoriNaoya Masumori More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2016.02.1037AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Several studies have shown the impact of systemic inflammation on the prognosis in patients with various types of cancers, including urothelial carcinoma (UC). The aim of this study was to evaluate the prognostic significance of pretreatment inflammatory markers in patients with metastatic UC who underwent first-line gemcitabine plus cisplatin (GC) chemotherapy. METHODS We reviewed the medical records of 214 metastatic UC patients who received first-line GC at 14 institutions between 2005 and 2014. The associations of pretreatment clinical factors, including the neutrophil-to-lymphocyte ratio (NLR), derived NLR, platelet-to-lymphocyte ratio, Onodera's prognostic nutritional index and C-reactive protein (CRP), with progression-free survival (PFS) and overall survival (OS) were assessed. The Cox proportional hazards model was used for multivariate analysis. RESULTS After excluding 27 patients with missing data, 187 patients were finally enrolled. The median PFS and OS were 7.5 months (IQR 3.6-11.9) and 11.7 months (IQR 7.3-19.9), respectively. Multivariate analysis showed that pretreatment CRP ≥ 1.0 mg/dL and liver or bone metastasis were independent poor prognostic factors for PFS and OS (Table). A prognostic model predicting OS was constructed based on the number of these three variables present (0, 1 and 2). The classified patients showed significantly different OS (p < 0.0001, log-rank test, Figure) and Harrell's concordance index was 0.66 (95%CI 0.58 - 0.74). CONCLUSIONS Pretreatment CRP elevation is an independent poor prognostic factor for mUC in patients undergoing first-line GC chemotherapy. Our newly developed prognostic model using the pretreatment CRP is a good discriminator of OS in metastatic UC patients. © 2016FiguresReferencesRelatedDetails Volume 195Issue 4SApril 2016Page: e364 Advertisement Copyright & Permissions© 2016MetricsAuthor Information Takeshi Maehana More articles by this author Toshiaki Tanaka More articles by this author Tetsuya Shindo More articles by this author Atsushi Takahashi More articles by this author Naoki Ito More articles by this author Keisuke Taguchi More articles by this author Hiroshi Hotta More articles by this author Naoya Masumori More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...

MP27-07 APPARENT DIFFUSION COEFFICIENT AS A PROGNOSTIC BIOMARKER OF UPPER URINARY TRACT CANCER

INTRODUCTION AND OBJECTIVES: Several studies have shown the impact of systemic inflammation on the prognosis in patients with various types of cancers, including urothelial carcinoma (UC). The aim of this study was to evaluate the prognostic significance of pretreatment inflammatory markers in patients with metastatic UC who underwent first-line gemcitabine plus cisplatin (GC) chemotherapy. METHODS: We reviewed the medical records of 214 metastatic UC patients who received first-line GC at 14 institutions between 2005 and 2014. The associations of pretreatment clinical factors, including the neutrophil-to-lymphocyte ratio (NLR), derived NLR, platelet-tolymphocyte ratio, Onodera’s prognostic nutritional index and C-reactive protein (CRP), with progression-free survival (PFS) and overall survival (OS) were assessed. The Cox proportional hazards model was used for multivariate analysis. RESULTS: After excluding 27 patients with missing data, 187 patients were finally enrolled. The median PFS and OS were 7.5 months (IQR 3.6-11.9) and 11.7 months (IQR 7.3-19.9), respectively. Multivariate analysis showed that pretreatment CRP 1.0 mg/dL and liver or bone metastasis were independent poor prognostic factors for PFS and OS (Table). A prognostic model predicting OS was constructed based on the number of these three variables present (0, 1 and 2). The classified patients showed significantly different OS (p < 0.0001, log-rank test, Figure) and Harrell’s concordance index was 0.66 (95%CI 0.58 0.74). CONCLUSIONS: Pretreatment CRP elevation is an independent poor prognostic factor for mUC in patients undergoing first-line GC chemotherapy. Our newly developed prognostic model using the pretreatment CRP is a good discriminator of OS in metastatic UC patients. Source of Funding: none

Adjuvant effects of fermented red ginseng extract on advanced non-small cell lung cancer patients treated with chemotherapy.

To investigate the adjuvant therapeutic effects of fermented red ginseng (FRG) extract on non-small cell lung cancer (NSCLC) patients treated with chemotherapy. A total of 60 patients with advanced NSCLC were divided into two groups using a random number table, i.e., the gemcitabine plus cisplatin (GP) chemotherapy alone group (26 patients) and the FRG + GP chemotherapy group (34 patients), for 60-day treatment. Patients were then assessed according to the Fatigue Symptom Inventory, Chinese medicine symptoms score, Self-Rating Anxiety Scale, Self-Rating Depression Scale, Karnofsky Performance Status Scale, and Functional Assessment of Cancer Therapy-Lung. In addition, chemotherapy toxicity and tumor biomarkers were measured. For NSCLC patients after chemotherapy, FRG extract significantly improved the FSI score, CM symptoms score, psychological status, physical conditions, and quality of life and reduced chemotherapy toxicity, but the expression levels of carcinoembryonic antigen, cytokeratin-19 fragments, and neuron-specific enolase were not significantly different between the chemotherapy alone and the FRG + chemotherapy groups or between pre- and post-treatments. This study demonstrated that FRG extract had an adjuvant effect on advanced NSCLC patients treated with chemotherapy. Further studies with a larger sample size will verify the current findings.

Sequential Cytokine-Induced Killer Cell Immunotherapy Enhances the Efficacy of the Gemcitabine Plus Cisplatin Chemotherapy Regimen for Metastatic Nasopharyngeal Carcinoma

In this study, we investigated the efficacy of sequential cytokine-induced killer cell (CIK) immunotherapy with gemcitabine plus cisplatin (GC) regimen chemotherapy in metastatic nasopharyngeal carcinoma (NPC) patients. Between September 2006 and April 2010, 222 NPC patients with distant metastasis after radiotherapy completion were retrospectively analyzed: 112 patients received 4–6 cycles of GC chemotherapy at 4-week intervals, followed by at least 4 cycles of CIK immunotherapy at 2-week intervals (GC+CIK group); the remaining 110 patients received 4–6 cycles of GC chemotherapy alone (GC group). The evaluation of long-term efficacy showed that the progression-free survival (PFS) rate was significantly higher in the GC+CIK group (log-rank test; p = 0.009), as was the overall survival (OS) rate (p = 0.006). In conclusion, sequential CIK treatment may be effective in enhancing the therapeutic efficacy of GC chemotherapy for metastatic NPC patients. This study provides a basis for alternative therapeutic strategies for metastatic NPC.

Gemcitabine plus Cisplatin versus Capecitabine plus Cisplatin as First-Line Chemotherapy for Advanced Biliary Tract Cancer: A Retrospective Cohort Study

Background and Aim: Gemcitabine plus cisplatin (GP) is a standard chemotherapy option for patients with advanced biliary tract cancer (BTC). We compared the efficacy and safety of capecitabine plus cisplatin (XP) versus GP in advanced BTC. Methods: The records of all patients treated with GP or XP chemotherapy for unresectable, metastatic, or recurrent BTC at the National Cancer Center between December 2001 and August 2012 were reviewed retrospectively. Patients with histologically confirmed intrahepatic cholangiocarcinoma, gallbladder cancer, or extrahepatic cholangiocarcinoma were enrolled. Results: Of the 344 patients enrolled, 127 received GP and 217 received XP. At a median follow-up time of 8.9 months, the median time to progression was longer in the GP group than in the XP group (5.6 vs. 4.7 months), but the difference was not statistically significant (p = 0.081). The median overall survival (OS) was 8.4 months (95% CI 6.2-10.7) in the GP group and 7.6 months (95% CI 6.8-8.7) in the XP group (p = 0.024), with statistical significance retained following multivariate analysis (HR 0.72; 95% CI 0.527-0.987; p = 0.004). Grade 3/4 toxicities were significantly more frequent in the GP group than in the XP group (40.9 vs. 24.9%, p = 0.002). Conclusions: GP was superior to XP in prolonging OS, despite increasing the rate of grade 3/4 adverse events.

Comparison between neoadjuvant and adjuvant gemcitabine plus cisplatin chemotherapy for muscle‐invasive bladder cancer

Aim: Radical cystectomy plus platinum-based perioperative chemotherapy is a standard treatment for patients with clinically localized muscle-invasive bladder cancer. The standard perioperative chemotherapy is methotrexate, vinblastine, doxorubicin and cisplatin (MVAC). However, no prospective randomized trial has been published that compares neoadjuvant and adjuvant chemotherapy for bladder cancer. Moreover, the efficacy of perioperative chemotherapy with gemcitabine plus cisplatin (GC) has not been clarified. In this study we have compared the clinical outcomes between neoadjuvant and adjuvant chemotherapy in patients receiving GC.Methods: We retrospectively reviewed the records of patients who were scheduled to be treated with a radical cystectomy plus perioperative chemotherapy with GC from 2005 to 2010 at our institution. The primary outcome measure was recurrence-free survival (RFS).Results: A total of 42 patients received perioperative chemotherapy with GC (25 neoadjuvant, 17 adjuvant). The median number of cycles of GC administered to the two groups was not significantly different. The median duration of follow up was 28.6 months. During the follow-up period, recurrence was observed in nine and three patients in the neoadjuvant and adjuvant groups, respectively. The RFS rate at median follow up was 67 and 76% in the neoadjuvant and adjuvant groups, respectively. No significant difference in RFS at median follow up was observed between the two groups (P = 0.124).Conclusion: Our results showed no statistically significant difference in RFS between neoadjuvant and adjuvant GC chemotherapy for muscle-invasive bladder cancer. We expect to validate these findings in a prospective randomized trial.

Thermo-chemotherapy of GP or TP for advanced non-small cell lung cancer: a systematic review

背景与目的中晚期非小细胞肺癌（non-small cell lung cancer, NSCLC）的治疗效果较差，生存期也较短，临床研究显示化疗与热疗的联合疗法效果较好。本研究通过系统评价吉西他滨联合铂类（Gemcitabine and Cisplatin, GP）或紫杉醇联合铂类（Paclitaxel and Cisplatin, TP）方案化疗联合热疗治疗NSCLC的疗效及安全性，为临床实践与研究提供参考。方法计算机检索Cochrane Library、PubMed、EMBASE和中国生物医学文献数据库、中国期刊全文数据库、中文科技期刊数据库、数字化期刊全文数据库，同时辅以其它检索。收集所有比较GP或TP化疗联合热疗与单纯GP或TP化疗的随机对照试验（randomized controlled trial, RCT）。选择适当的质量评价标准对纳入文献进行质量评价，使用RevMan 5.1软件进行meta分析。结果共纳入15篇RCT，共952例NSCLC。Meta分析结果显示，化疗联合热疗组的生活质量改善率（OR=3.84, 95%CI: 2.61-5.64）、1年生存率（HR=1.94, 95%CI: 1.21-3.12）和2年生存率（HR=2.05, 95%CI: 1.18-3.58）均好于单纯化疗组，差异均有统计学意义（P < 0.05）；热化组与单化组的骨髓抑制、胃肠反应、肝肾损害以及腹泻发生率的差异均无统计学意义（P > 0.05）。结论相较于单纯化疗，GP或TP方案化疗联合热疗能提高中晚期NSCLC患者生存率和近期疗效，改善症状，提高患者的生活质量，且并不增加毒副反应，但本文结论尚需大样本高质量RCT进一步验证。