Multicenter Retrospective Analysis of Original versus Modified FOLFIRINOX in Metastatic Pancreatic Cancer: Results of the NAPOLEON Study.

INTRODUCTION: Original FOLFIRINOX (oFFX) is more toxic than other regimens for patients with metastatic pancreatic cancer (mPC); therefore, a modified FFX (mFFX) regimen with a reduced dosage has been used in Japanese clinical practice. However, very few studies have compared these two regimens. METHODS: This study was conducted as part of a multicenter retrospective study of 318 patients with mPC across 14 centers in Japan (NAPOLEON study). To control for potential bias and confounders, we conducted a propensity score-adjusted analysis of patient characteristics and clinical outcomes. RESULTS: oFFX and mFFX were administered to 48 and 54 patients. More patients with younger age and poorer performance status were included in the oFFX group. The overall survival (OS; median, 11.6 vs. 11.3 months; hazard ratio [HR], 0.91; 95% confidence interval [CI], 0.60-1.40; p = 0.67), progression-free survival (PFS) (median, 6.3 vs. 5.7 months; HR, 0.85; 95% CI, 0.56-1.28; p = 0.44), and overall response rate (29 vs. 26%, p = 0.71) were not significantly different for the oFFX and mFFX groups. Thrombopenia and liver dysfunction were significantly more frequent with oFFX than with mFFX. The median received dose intensity of CPT-11 was higher with oFFX than with mFFX (299 vs. 270 mg/m2/week, p < 0.01). The propensity score-adjusted analysis revealed no statistically significant differences in OS and PFS between the two groups. CONCLUSION: In our data, there was no significant difference in efficacy between mFFX and oFFX, and mFFX has fewer adverse events.

Scoring model with serum albumin and CA19-9 for metastatic pancreatic cancer in second-line treatment: results from the NAPOLEON study.

BACKGROUND: Patients with metastatic pancreatic cancer refractory to first-line chemotherapy (CTx) have few treatment options. It is unclear what kind of patients could be brought about survival benefit by 2nd-line CTx after refractory to gemcitabine + nab-PTX (GnP) or FOLFIRINOX. METHODS: This analysis was conducted as part of a multicenter retrospective study of GnP or FOLFIRINOX in patients with metastatic pancreatic cancer. Excluding censored cases, 156 and 77 patients, respectively, received second-line chemotherapy (CTx) and best supportive care (BSC). Using prognostic factors for post-discontinuation survivals (PDSs) at the first-line determination in multivariate analysis, we developed a scoring system to demonstrate the benefit of second-line CTx. RESULTS: The second-line CTx group had a median PDS of 5.2 months, whereas the BSC group had a median PDS of 2.7 months (hazard ratio 0.42; 95% confidence interval [CI] 0.31-0.57; p < 0.01). According to the Cox regression model, serum albumin levels below 3.5 g/dL, and CA19-9 levels above 1000 U/mL were independent prognostic factors (p < 0.01). Serum albumin (≥ and < 3.5 g/dL allotted to scores 0 and 1) and CA19-9 (< and ≥ 1000 U/mL allotted to scores 0 and 1) at first-line determination were used to develop the scoring system. The PDSs of patients with scores of 0 and 1 were significantly better than those of the BSC group; however, there was no significant difference between the PDSs of patients with score 2 and the BSC group. CONCLUSION: The survival advantage of second-line CTx, was observed in patients with scores of 0 and 1 but not in those with score 2.

Prognostic nomogram for patients with unresectable pancreatic cancer treated with gemcitabine plus nab-paclitaxel or FOLFIRINOX: A post-hoc analysis of a multicenter retrospective study in Japan (NAPOLEON study).

BACKGROUND: No reliable nomogram has been developed until date for predicting the survival in patients with unresectable pancreatic cancer undergoing treatment with gemcitabine plus nab-paclitaxel (GnP) or FOLFIRINOX. METHODS: This analysis was conducted using clinical data of Japanese patients with unresectable pancreatic cancer undergoing GnP or FOLFIRINOX treatment obtained from a multicenter study (NAPOLEON study). A Cox proportional hazards model was used to identify the independent prognostic factors. A nomogram to predict 6-, 12-, and 18-month survival probabilities was generated, validated by using the concordance index (C-index), and calibrated by the bootstrapping method. And then, we attempted risk stratification for survival by classifying the patients according to the sum of the scores on the nomogram (total nomogram points). RESULTS: A total of 318 patients were enrolled. A prognostic nomogram was generated using data on the Eastern Cooperative Oncology Group performance status, liver metastasis, serum LDH, serum CRP, and serum CA19-9. The C-indexes of the nomogram were 0.77, 0.72 and 0.70 for 6-, 12-, and 18-month survival, respectively. The calibration plot showed optimal agreement at all points. Risk stratification based on tertiles of the total nomogram points yielded clear separations of the survival curves. The median survival times in the low-, moderate-, and high-risk groups were 15.8, 12.8 and 7.8 months (P<0.05), respectively. CONCLUSIONS: Our nomogram might be a convenient and inexpensive tool to accurately predict survival in Japanese patients with unresectable pancreatic cancer undergoing treatment with GnP or FOLFIRINOX, and will help clinicians in selecting appropriate therapeutic strategies for individualized management.

A multicenter propensity score analysis of FOLFIRINOX vs gemcitabine plus nab-paclitaxel administered to patients with metastatic pancreatic cancer: results from the NAPOLEON study.

PURPOSE: Fluorouracil, leucovorin, irinotecan, and oxaliplatin (FOLFIRINOX, FFX) and gemcitabine plus nab-paclitaxel (GnP) are considered standard treatments for patients with metastatic pancreatic cancer. Direct comparisons are not available that establish which is optimal. METHODS: We conducted a propensity score-adjusted analysis of patients with metastatic pancreatic cancer to identify the therapeutic advantages of these standard therapies. We used clinical data as part of a multicenter retrospective study of patients with unresectable or recurrent pancreatic cancer treated with FFX or GnP (NAPOLEON study). RESULTS: FFX and GnP were initially administered to 102 and 153 patients, respectively. The GnP group comprised more patients of advanced age, worse performance status, lower body mass index, recurrence, and lower albumin concentrations. Median overall survival (OS) and progression-free survival (PFS) were 11.5 months and 5.8 months in the FFX group and 11.1 months and 5.9 months in the GnP group, respectively. Propensity score-adjusted analysis indicated that the administration of FFX or GnP was not independently associated with OS (adjusted hazard ratio [HR] 1.06; 95% confidence interval [CI] 0.76-1.47; P = 0.73). Similarly, the difference in PFS was not significant between groups (adjusted HR 0.93; 95% CI 0.68-1.26; P = 0.62). Gastrointestinal disorders were more common in the FFX group, whereas the frequencies of hematological, nervous system, and skin disorders were higher in the GnP group. CONCLUSION: The efficacies of FFX and GnP were comparable, although safety profiles differed and should be considered in selecting treatment.

Mechanisms of PKC-Mediated Enhancement of HIF-1α Activity and its Inhibition by Vitamin K2 in Hepatocellular Carcinoma Cells.

Hypoxia-inducible factor 1 (HIF-1) plays important roles in cancer cell biology. HIF-1α is reportedly activated by several factors, including protein kinase C (PKC), in addition to hypoxia. We investigated the role of PKC isoforms and the effects of vitamin K2 (VK2) in the activation process of HIF-1α. Human hepatocellular carcinoma (HCC)-derived Huh7 cells were cultured under normoxic and hypoxic (1% O2) conditions with or without the PKC stimulator TPA. The expression, transcriptional activity and nuclear translocation of HIF-1α were examined under treatment with PKC inhibitors, siRNAs against each PKC isoform and VK2. Hypoxia increased the expression and activity of HIF-1α. TPA increased the HIF-1α activity several times under both normoxic and hypoxic conditions. PKC-δ siRNA-mediated knockdown, PKC-δ inhibitor (rottlerin) and pan-PKC inhibitor (Ro-31-8425) suppressed the expression and transcriptional activity of HIF-1α. VK2 significantly inhibited the TPA-induced HIF-1α transcriptional activity and suppressed the expression and nuclear translocation of HIF-1α induced by TPA without altering the HIF-1α mRNA levels. These data indicate that PKC-δ enhances the HIF-1α transcriptional activity by increasing the nuclear translocation, and that VK2 might suppress the HIF-1α activation through the inhibition of PKC in HCC cells.

Effects of home-based exercise and branched-chain amino acid supplementation on aerobic capacity and glycemic control in patients with cirrhosis.

AIM: The aim of the current study is to examine whether home-based step exercise at anaerobic threshold (AT) and branched-chain amino acid (BCAA) supplementation improve aerobic capacity, ectopic fat in liver and muscle, and glycemic control in patients with liver cirrhosis. METHODS: Six female patients with compensated liver cirrhosis received oral BCAA and were instructed to undertake bench step exercises at an intensity that corresponded to AT, with a goal of performing 140 min of exercise per week at home for 12 months. Fat deposition in liver (liver to spleen ratio) and intramuscular adipose tissue content were assessed at baseline and after 6 and 12 months by computed tomography. Glycemic control indices (homeostasis model assessment of insulin resistance, hemoglobin A1c [HbA1c ], glycated albumin [GA] and chronic liver disease [CLD]-HbA1c [average of HbA1c and GA/3]) were also measured. RESULTS: Twelve months of moderate training significantly increased AT, which is an index of aerobic capacity, but no changes were observed in body weight, liver to spleen ratio, or intramuscular adipose tissue content. Glycated albumin significantly decreased (P < 0.05) and there tended to be a similar decrease in CLD-HbA1c (P < 0.1) after the exercise. The baseline serum triglyceride level correlated with changes in GA (P < 0.01) and CLD-HbA1c (P < 0.1). CONCLUSION: The current results suggest that the combination of home-based step exercise at AT and BCAA supplementation enhances aerobic capacity and potentially improves glycemic control in patients with cirrhosis without changes in body weight. The baseline serum serum triglyceride may partially explain the degree of improvement in glycemic control with exercise and BCAA intervention.

Seropositivity and Titers of Anti-Smooth Muscle Actin Antibody Are Associated with Relapse of Type 1 Autoimmune Hepatitis.

BACKGROUND It is important to avoid relapse in autoimmune hepatitis (AIH) because repeated multiple relapses have been associated with a worse prognosis. However, risk factors for relapse before initiation of treatment are not fully understood. The aim of this study was to find predictive markers for relapse of type 1 AIH. MATERIAL AND METHODS We reviewed the records of 53 patients diagnosed with type 1 AIH based on the revised scoring system proposed by the International Autoimmune Hepatitis Group (IAIHG) between 2009 and 2014 at 4 hospitals belonging to the Saga Study Group of Liver Diseases (SASLD). We analyzed the differences in background characteristics between patients with or without relapse. RESULTS All patients achieved remission after treatment, and 9 (17%) subsequently relapsed. The relapsed patients were significantly younger and had a higher positive rate of anti-smooth muscle antibody (ASMA) than the non-relapsed patients (100% vs. 25%, P=0.0012). Moreover, relapse rate increased with titer of ASMA, while titer of antinuclear antibody was not associated with relapse rate. CONCLUSIONS ASMA is a useful predictive marker for relapse of type 1 AIH during or after withdrawal of medical therapy. More careful attention should be paid to immunosuppressive therapy in patients with high titers of ASMA.

Sarcopenia is a risk factor for the recurrence of hepatocellular carcinoma after curative treatment.

BACKGROUND AND AIM: Sarcopenia, initially proposed as decreased of muscle mass and strength, is associated with aging and malignant diseases. The aim of the present study was to determine whether there is a correlation between sarcopenia and the recurrence of hepatocellular carcinoma (HCC) after curative treatment. METHODS: We conducted a retrospective analysis of consecutive naive patients with HCC who underwent curative resection or radiofrequency ablation. To eliminate the influence of cause or the severity of liver damage, subjects were limited to those with HCC with hepatitis C-related cirrhosis and Child-Pugh class A liver function. Patients were assessed using computed tomographic measurement of muscle mass at the level of the third lumbar (L3) vertebrae, the L3 skeletal muscle index (L3 SMI). Sarcopenia was defined by using previously published, sex-specific cut-off value. RESULTS: Sarcopenia was present in 61 of 92 patients. Patients' median age was 71.5 years (range, 47-84), and the baseline characteristics of patients were comparable between patients with and without sarcopenia except for sex, serum albumin level, prothrombin time, diabetes mellitus and body mass index. Recurrence rates at 1, 3 and 5 years were 39.1%,77.1%,81.7% for patients with sarcopenia and 23.5%,59.5% and 75.7% for patients without sarcopenia, respectively (P = 0.03). Multivariate Cox analysis revealed that sarcopenia and preoperative α-fetoprotein of more than 40 ng/mL were significant independent factors for recurrence. CONCLUSION: Sarcopenia is a risk factor for recurrence in patients with HCC who were treated with curative treatment.

Evidence-based clinical practice guidelines for nonalcoholic fatty liver disease/nonalcoholic steatohepatitis.

Nonalcoholic fatty liver disease (NAFLD) is currently the most common cause of chronic liver disease in industrialized countries worldwide, and has become a serious public health issue not only in Western countries but also in many Asian countries including Japan. Within the wide spectrum of NAFLD, non-alcoholic steatohepatitis (NASH) is a progressive form of disease, which often develops into liver cirrhosis and increases the risk of hepatocellular carcinoma. In turn, a large proportion of NAFLD/NASH is the liver manifestation of metabolic syndrome, suggesting that NAFLD/NASH plays a key role in the pathogenesis of systemic atherosclerotic diseases. Currently, a definite diagnosis of NASH requires liver biopsy, though various non-invasive measures are under development. The mainstays of prevention and treatment of NAFLD/NASH include dietary restriction and exercise; however, pharmacological approaches are often necessary. Currently, vitamin E and thiazolidinedione derivatives are the most evidence-based therapeutic options, although the clinical evidence for long-term efficacy and safety is limited. This practice guideline for NAFLD/NASH, established by the Japanese Society of Gastroenterology in cooperation with The Japan Society of Hepatology, covers lines of clinical evidence reported internationally in the period starting from 1983 through January 2012, and each clinical question was evaluated using the GRADE system. Based on the primary release of the full version in Japanese, this English summary provides the core essentials of this clinical practice guideline comprising the definition, diagnosis, and current therapeutic recommendations for NAFLD/NASH in Japan.

[Hepatocellular carcinoma and vitamin K2].

Despite recent progress in diagnosis and therapy, hepatocellular carcinoma(HCC)remains among the cancers with the poorest prognoses. Vitamin Ks(VKs)have been shown to suppress the growth of HCC cells. Long-term administration of VK2 has established its clinical safety, but it does not appear to exhibit marked anti-tumor effects when administered alone. For more effective use of VK2 against HCC, co-administration of VK2 with other proven anticancer agents or development of a new VK preparation with a modified side-chain should be investigated in the future.

Efficacy of ezetimibe for reducing serum low-density lipoprotein cholesterol levels resistant to lifestyle intervention in patients with non-alcoholic fatty liver disease.

AIM: To investigate the efficacy of ezetimibe and lifestyle intervention for treating patients with non-alcoholic fatty liver disease (NAFLD) and residual dyslipidemia via a combination of ezetimibe and lifestyle intervention. METHODS: Patients with NAFLD with residual dyslipidemia after a 6-month lifestyle intervention program were included. After completion of the 6-month program, the patients received p.o. administration of ezetimibe at 10 mg/day, in addition to lifestyle intervention, for 6 months. RESULTS: Of the 59 patients with NAFLD who had participated in the 6-month lifestyle intervention program between 2007 and 2012, 21 with residual dyslipidemia (10 males and 11 females) were enrolled. Median age was 58 years (range, 27-75), median bodyweight was 63.0 kg (range, 39.4-109.0), median body mass index was 25.4 kg/m2 (range, 18.2-37.1), median alanine aminotransferase was 23 IU/L (14-73), median high-density lipoprotein (HDL) was 58 mg/dL (range, 37-93), median triglycerides (TG) was 105 mg/dL (range, 42-216) and median low-density lipoprotein (LDL) was 153 (66-209) mg/dL. After 6 months of treatment with ezetimibe, serum LDL levels were improved in 15 of 20 (75%) patients (P = 0.0015), while no improvements were observed in the remaining five patient (25%). Ezetimibe was discontinued in one patient who developed skin rash. CONCLUSION: Ezetimibe is effective for treating residual dyslipidemia after lifestyle intervention in patients with NAFLD.

[A case of multiple liver abscesses associated with Streptococcus salivarius in a patient with chronic periodontitis].

Streptococcus salivarius is an oral commensal bacterium that rarely causes disease in humans. Here, we report a case of liver abscess associated with S. salivarius in a 41-year-old woman who presented with continuous abdominal discomfort, fatigue, and fever. She was diagnosed with multiple liver abscesses; she underwent percutaneous transhepatic abscess drainage. Thereafter, S. salivarius was isolated in all bacterial cultures of the drained abscesses, and it was sensitive to penicillins. She made a good recovery after treatment. In the absence of an infective source other than chronic periodontitis, the cause of liver abscesses was attributed to oral S. salivarius. S. salivarius is a normal oral commensal, and oral commensals must be considered if the infective origin of liver abscess cannot be determined.

A multicenter retrospective observational NAPOLEON2 study of nanoliposomal irinotecan with fluorouracil and folinic acid in patients with unresectable pancreatic cancer.

Nanoliposomal irinotecan with fluorouracil and folinic acid (NFF) is a standard regimen after gemcitabine-based therapy for patients with unresectable or recurrent pancreatic cancer. However, there are limited clinical data on its efficacy and safety in the real-world. We therefore initiated a retrospective and prospective observational study (NAPOLEON-2). The results of the retrospective part were reported herein. In this retrospective study, we evaluated 161 consecutive patients who received NFF as second-or-later-line regimen. The main endpoint was overall survival (OS), and the other endpoints were response rate, disease control rate, progression-free survival (PFS), dose intensity, and adverse events (AEs). The median age was 67 years (range, 38-85 years). The median OS and PFS were 8.1 and 3.4 months, respectively. The objective response and disease control rates were 5% and 52%, respectively. The median relative dose intensity was 81.6% for nanoliposomal irinotecan and 82.9% for fluorouracil. Grade 3 or 4 hematological and nonhematological AEs occurred in 47 and 42 patients, respectively. Common grade 3 or 4 AEs included neutropenia (24%), anorexia (12%), and leukocytopenia (12%). Subanalysis of patients treated with second-line and third-or-later-line demonstrated no statistical significant difference in OS (7.6 months vs. 9.1 months, respectively; hazard ratio, 0.92; 95% confidence interval, 0.64-1.35; p = 0.68). In conclusion, NFF has acceptable efficacy and safety profile even in real-world clinical settings. The prospective study is in progress to validate these findings.

Nutritional status and quality of life in current patients with liver cirrhosis as assessed in 2007-2011.

AIM: Current guidelines recommended adequate nutritional support for patients with liver cirrhosis to improve clinical outcome and quality of life (QOL). However, these evidences were obtained more than 10 years ago when malnutrition prevailed. In recent years, the impact of obesity on liver damage and carcinogenesis has grown. We attempted to elucidate the nutritional state and QOL in present cirrhotics. METHODS: A research group supported by the Ministry of Health, Labor and Welfare of Japan recruited 294 cirrhotics between 2007 and 2011. Subjects comprised 171 males and 123 females, 158 of whom had hepatocellular carcinoma (HCC) and Child-Pugh grades A : B : C were 154:91:49. Anthropometry, blood biochemistry and indirect calorimetry were conducted, and QOL was measured using Short Form-8. RESULTS: The mean body mass index (BMI) of all patients was 23.1 ± 3.4 kg/m(2) , and 31% showed obesity (BMI ≥ 25.0). In subjects without ascites, edema or HCC, mean BMI was 23.6 ± 3.6, and 34% had obesity. Protein malnutrition defined as serum albumin of less than 3.5 g/dL and energy malnutrition as respiratory quotient of less than 0.85 appeared in 61% and 43%, respectively, and protein-energy malnutrition (PEM) in 27% of all subjects. Among subjects without HCC, each proportion was 67%, 48% and 30%, respectively. QOL was significantly lower on all subscales than Japanese national standard values, but was similar regardless the presence or absence of HCC. CONCLUSION: While PEM is still present in liver cirrhosis, an equal proportion has obesity in recent patients. Thus, in addition to guidelines for PEM, establishment of nutrition and exercise guidelines seems essential for obese patients with liver cirrhosis.

Severity of non-alcoholic steatohepatitis is associated with substitution of adipose tissue in skeletal muscle.

BACKGROUND AND AIMS: The pathogenesis of non-alcoholic fatty liver disease (NAFLD) is now focusing on its organ cross-talk with not only adipose tissue but also systemic skeletal muscle. Cross-sectional and longitudinal studies were conducted to determine the role of intramuscular adipose tissue content (IMAC) measured by computed tomography on the severity of NAFLD/non-alcoholic steatohepatitis (NASH). METHODS: Two hundred eight Japanese patients with NAFLD/NASH diagnosed by liver biopsy were enrolled into a cross-sectional study. Twenty-one patients were enrolled in a longitudinal study and received a programmed diet and exercise intervention, in some cases the combination of pharmacotherapy. We measured IMAC in the multifidus muscle and biochemical parameters, and conducted liver histology to assess NAFLD/NASH status. RESULTS: Histopathological stage in terms of simple steatosis and Brunt's classification was significantly correlated with IMAC (P < 0.01). Multivariate logistic regression analysis indicated that risk factors associated with the severity of NASH were IMAC and aging (IMAC: odds ratio = 2.444, P < 0.05; Age: odds ratio = 2.355, P < 0.05). The interventions improved histopathological changes in 11 patients with NASH as well as IMAC. CONCLUSION: These results suggest that skeletal muscle fat accumulation may have been linked to the pathogenesis and severity of NASH.

Survival advantage of radiofrequency ablation for hepatocellular carcinoma: comparison with ethanol injection.

BACKGROUND/AIMS: The aims of this study were to compare long-term prognosis of patients with hepatocellular carcinoma (HCC) treated with radiofrequency ablation (RFA) and percutaneous ethanol injection (PEI). METHODOLOGY: Two hundred and thirteen patients with HCC were initially treated with PEI or RFA at Saga University Hospital between 1990 and 2004. The present study included 190 patients: 98 treated with PEI from 1990 to 1999, and 92 with RFA from 2000 to 2004. The association of treatment method with survival prognosis was evaluated by multivariate analysis. RESULTS: There were no significant differences in gender, etiology, and tumor stage between the two groups. Five-year survival rate in the PEI group was 40% and 51% in the RFA group. According to tumor stage, there were no differences in 5-year survival rate between the two groups for tumor stage I and III. For stage II patients, RFA had better survival than PEI (48% vs. 28%, p = 0.03). Multivariate analysis indicated that RFA was more effective for long-term survival than PEI in patients with tumor stage II (p = 0.04). CONCLUSIONS: Compared to PEI, RFA improved survival in patients with stage II HCC, indicating a therapeutic advantage of RFA.

Evaluation narcotic analgesic use and survival time in terminal stage liver diseases compared with lung cancer: a retrospective chart review.

Hepatocellular carcinoma (HCC) and liver cirrhosis are fatal diseases. This study aimed to investigate survival time and palliative care in terminal HCC and/or liver cirrhosis compared with lung cancer. Between January 2004 and December 2010, we enrolled 116 patients with terminal cirrhosis and/or HCC or lung cancer admitted to a municipal hospital in Japan; 48 had liver cirrhosis, 35 HCC and 33 lung cancer. By retrospective chart review, we evaluated: (i) rate of usage of narcotic analgesics and (ii) survival time from onset of coma (Glasgow Coma Scale less than 8). Time between coma and death was significantly shorter in the liver disease patients (cirrhosis and/or HCC: 7.0 h) than in lung cancer (44.0 h, p = 0.045). Total bilirubin was higher in HCC compared with cirrhosis (p<0.01). Rate of usage of narcotic analgesics was higher in lung cancer (20/33: 60.6%) than in liver disease (17/83: 20.5%, p<0.01); analgesics were used more frequently in HCC than in liver cirrhosis (p<0.01). These results suggest that liver cirrhosis and HCC patients do not always require palliative care and that survival time from onset of coma due to liver disease was not prolonged compared with lung cancer.

C-reactive protein/albumin ratio is the most significant inflammatory marker in unresectable pancreatic cancer treated with FOLFIRINOX or gemcitabine plus nab-paclitaxel.

There are limited absolute biomarkers for determining the prognosis before first- and second-line palliative chemotherapy in unresectable pancreatic cancer (urPC) patients. To find the best prognostic inflammatory marker, we investigated relationships between overall survival (OS) and six inflammatory markers; C-reactive protein/albumin ratio (CAR), neutrophil-lymphocyte ratio (NLR), prognostic nutrition index (PNI), platelet-lymphocyte ratio (PLR), Glasgow prognostic score (GPS), and prognostic index (PI). We examined 255 patients who received gemcitabine + nab-paclitaxel or FOLFIRINOX as first-line chemotherapy and 159 patients who subsequently underwent second-line chemotherapy. First-line patients with lower CAR had better OS compared to those with a higher CAR (hazard ratio 0.57; 95% confidential index 0.42-77; P < 0.01). Similarly, lower NLR (P = 0.01), higher PNI (P = 0.04), lower PLR (P = 0.03), GPS score of 0 (P < 0.01) and PI score of 0 (P < 0.01) were all associated with better OS. CAR demonstrated the best superiority for determining survival prognosis through the use of area under the curve of time-dependent receiver-operating characteristic curves. Furthermore, a lower CAR before second-line therapy exhibited better OS versus higher CAR (P < 0.01). Therefore, CAR might be a useful biomarker for predicting urPC patient prognosis in both first- and second-line chemotherapy.