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.

Subnanomolar Sensitive Stable Isotopic Determination in CO2 by Tunable Infrared Laser Absorption Spectroscopy.

Oxygen and carbon stable isotope ratios (18O/16O, 13C/12C, and 17O/16O) of CO2 have been crucial in helping us understand Earth and planetary systems. These ratios have also been used in medicine for the noninvasive diagnosis of diseases from exhaled breath and for quantifying biochemical or metabolic reactions and in determining the production area of agricultural products. The current method for measuring the stable isotope ratios of CO2 is primarily gas-source isotope ratio mass spectroscopy (IRMS). Due to the recent demand for isotopic microanalysis of carbonates and organic compounds, the sample size required for isotopic measurements has been reduced to approximately 2 nmol CO2 (equivalent to 0.2 µg CaCO3 and 24 ng carbon) by using high-precision IRMS. We report a novel method using tunable mid-infrared laser direct absorption spectroscopy (TILDAS) for sensitive measurements of 18O/16O and 13C/12C in subnanomolar CO2. This method can accurately measure 18O/16O and 13C/12C in CO2 with a repeatability of less than 0.03‰ (n = 28) in a range of 0.3 nmol (equivalent to 0.03 µg CaCO3 and 3.8 ng carbon) to 30 nmol. This is a sample size 1 order of magnitude smaller than currently available sensitive analytical techniques. In addition, the TILDAS system measures 17O/16O simultaneously with a repeatability of less than 0.06‰ (n = 28). Our method is a major advance in supersensitive CO2 stable isotopic analyses for various fields.

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.

Multicenter retrospective analysis of systemic chemotherapy for unresectable combined hepatocellular and cholangiocarcinoma.

We conducted a multicenter retrospective analysis to evaluate the efficacy of systemic chemotherapy for unresectable combined hepatocellular and cholangiocarcinoma. We enrolled 36 patients with pathologically proven, unresectable combined hepatocellular and cholangiocarcinoma treated with systemic chemotherapy. The log-rank test determined the significance of each prognostic factor. Elevated alpha-fetoprotein, carcinoembryonic antigen and carbohydrate antigen 19-9 levels were observed in 58.3%, 16.7% and 38.9% of patients, respectively. First-line chemotherapy included platinum-containing regimens consisting of gemcitabine/cisplatin (n = 12) and fluorouracil/cisplatin (n = 11), sorafenib (n = 5) and others (n = 8). The median overall and progression-free survival times were 8.9 and 2.8 months, respectively, with an overall response rate of 5.6%. Prognostic factors associated with negative outcomes included poor performance status, no prior primary tumor resection, a Child-Pugh class of B, and elevated carcinoembryonic antigen levels with a hazard ratio of 2.25, 2.48, 3.25 and 2.84 by univariate analysis, respectively. The median overall survival times of the gemcitabine/cisplatin, fluorouracil/cisplatin, sorafenib and other groups were 11.9, 10.2, 3.5 and 8.1 months, respectively. Multivariate analysis revealed that the overall survival of patients within the sorafenib monotherapy group was poor compared with platinum-containing regimens (HR: 15.83 [95% CI: 2.25-111.43], P = .006). All 7 patients in the sorafenib group had progressive disease, including 2 patients with second-line therapy. In conclusion, the platinum-containing regimens such as gemcitabine/cisplatin were associated with more favorable outcomes than sorafenib monotherapy for unresectable combined hepatocellular and cholangiocarcinoma.

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.

Phase I study of nintedanib in Japanese patients with advanced hepatocellular carcinoma and liver impairment.

This phase I, dose-escalation study evaluated the safety, preliminary efficacy and pharmacokinetics of nintedanib, a triple angiokinase inhibitor, in Japanese patients with advanced hepatocellular carcinoma and mild/moderate liver impairment. Thirty patients with unresectable hepatocellular carcinoma were enrolled to groups, depending on whether liver impairment was mild (group I, aspartate aminotransferase and alanine aminotransferase ≤2× upper limit of normal and Child-Pugh score 5 [n = 14] or 6 [n = 2]) or moderate (group II, Child-Pugh score 5-6 and aspartate aminotransferase or alanine aminotransferase >2× to ≤5× upper limit of normal [n = 7] or Child-Pugh score 7 [n = 7]); 22 patients had prior sorafenib treatment. Nintedanib was given twice daily in 28-day cycles until disease progression or unacceptable adverse events, starting at 150 mg (group I) or 100 mg (group II) and escalating to 200 mg. The primary objective was to define the maximum tolerated dose based on occurrence of dose-limiting toxicities during cycle 1 (grade ≥3 non-hematological and grade 4 hematological adverse events). No dose-limiting toxicities were reported during cycle 1 and the maximum tolerated dose for both groups was 200 mg twice daily. The most frequent adverse events were gastrointestinal (diarrhea, nausea, vomiting, and decreased appetite). No patients discontinued nintedanib due to adverse events; 31% of group I and 21% of group II had dose reductions. Median time to progression was 2.8 months (95% confidence interval, 1.05-5.52) for group I and 3.2 months (95% confidence interval, 0.95-6.70) for group II. Nintedanib showed a manageable safety profile and efficacy signals, including in patients previously treated with sorafenib. Clinical trial registration NCT01594125; 1199.120 (ClinicalTrials.gov).

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.

Pilot study of liraglutide effects in non-alcoholic steatohepatitis and non-alcoholic fatty liver disease with glucose intolerance in Japanese patients (LEAN-J).

AIM: Non-alcoholic fatty liver disease (NAFLD), a hepatic manifestation of metabolic syndrome, is associated with an increased risk of developing lifestyle-related diseases including type 2 diabetes, cardiovascular disease and cerebral vessel disease. No current drug therapy provides the ideal effects of decreasing hepatic inflammation while simultaneously improving liver fibrosis. Liraglutide is a glucagon-like peptide-1 receptor agonist that affects the histological findings in patients with non-alcoholic steatohepatitis (NASH). This study was conducted to evaluate the effect and action of liraglutide for biopsy-proven NASH. METHODS: After lifestyle modification intervention for 24 weeks, subjects whose hemoglobin A1c levels failed to improve to less than 6.0% and/or whose alanine aminotransferase levels were not lower than baseline, received liraglutide at 0.9 mg/body per day for 24 weeks. RESULTS: Of 27 subjects, 26 completed the lifestyle modification intervention. Nineteen subjects received liraglutide therapy for 24 weeks. Body mass index, visceral fat accumulation, aminotransferases and glucose abnormalities improved significantly. Repeated liver biopsy was performed in 10 subjects who continued liraglutide therapy for 96 weeks. Six subjects showed decreased histological inflammation as determined by NASH activity score and stage determined by Brunt classification. We saw no significant adverse events during therapy with liraglutide. CONCLUSION: Our pilot study demonstrated that treatment with liraglutide had a good safety profile and significantly improved liver function and histological features in NASH patients with glucose intolerance.

[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.

Nutritional Status Is Associated With Physical Improvement of Palliative Cancer Patients During Cancer Rehabilitation.

Background/Aim: Physical decline is accompanied with malnutrition in advanced cancer patients, thus nutritional care is often provided with cancer rehabilitation. However, a limited number of studies have focused on which nutritional index serves as an important marker to provide more intensive nutritional support for patients. Patients and Methods: We retrospectively reviewed advanced cancer patients who received chemotherapy and rehabilitation during hospitalization. In analysis 1, patients were divided into two groups: a Well group with caloric intake ≥ basal metabolism, calculated by the Harris-Benedict equation, and a Poor group with caloric intake less than their basal energy expenditure. The primary endpoint was the ratio of patients whose Eastern Cooperative Oncology Group Performance Status (ECOG PS) or Barthel index (BI) was maintained during rehabilitation. In analysis 2, the cohort was restratified into Responders, whose ECOG PS and BI improved, and Non-responders, comprising the remaining patients. Several nutritional indices were compared between the groups. Results: Eighty-four patients were evaluated in analysis 1, namely 51 Well patients and 33 Poor patients. The ECOG PS-maintained rate was 98% and 91% (p=0.29), and the BI-maintained rate was 100% and 88% (p=0.02) in the Well and Poor groups, respectively. In analysis 2, 72 patients were evaluated after excluding 12 patients who lacked nutritional data after rehabilitation. Compared with the Responders group, caloric intake appeared worse in the Non-responders group, although their nutritional background tended to be better. Conclusion: Insufficient caloric intake might be a predictive marker of poor outcomes after rehabilitation in advanced cancer patients.

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.

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.

Conversion Surgery for Unresectable Pancreatic Cancer Treated With FOLFIRINOX or Gemcitabine Plus Nab-paclitaxel.

BACKGROUND/AIM: Recent advances in chemotherapy have made significant progress in conversion surgery (CS) for unresectable pancreatic cancer (uPC). However, the success rate and efficacy of CS have not been fully demonstrated in patients with uPC treated with FOLFIRINOX (FFX) or gemcitabine plus nab-paclitaxel (GnP). PATIENTS AND METHODS: We retrospectively reviewed the records of 318 patients with uPC who received FFX or GnP as first-line chemotherapy. The efficacy in the CS group, defined as undergoing complete resection after chemotherapy, was analyzed, and compared with the non-CS group; then, contributing factors to achieving CS were extracted. We also analyzed differences in the efficacy of CS between locally advanced pancreatic cancer (LAPC) and metastatic pancreatic cancer (MPC). RESULTS: Overall, CS was achieved in 4.3% of cases, eight patients (13.3%) with LAPC and five (2.1%) with MPC. Contributing factors to CS were LAPC, no liver metastasis, CA19-9 ≤37, and chemotherapy response. After adjusting for these, overall survival was significantly better in the CS group than in the non-CS group [median of 32.9 vs. 11.3 months; adjusted hazard ratio (HR)=0.32; 95% confidence interval (CI)=0.14-0.70; p<0.01]. Median relapse-free survival duration after CS was 19.1 and 18.1 months in the LAPC-CS and MPC-CS group, respectively (p=0.84). The median post-conversion survival was 27.6 months in the entire CS group, 43.8 months in the LAPC-CS group and 21.3 months in the MPC-CS group. CONCLUSION: CS was achieved in 13.3% of LAPC and 2.1% of MPC cases. If possible, CS can markedly improve prognosis, even in MPC.

Efficacy of second-line chemotherapy after treatment with gemcitabine plus nab-paclitaxel or FOLFIRINOX in patients with metastatic pancreatic cancer.

First-line chemotherapy for patients with metastatic pancreatic cancer (MPC) includes gemcitabine plus nab-paclitaxel (GnP) and FOLFIRINOX (FFX). However, the efficacy of second-line chemotherapy and the role of combination chemotherapy in clinical practice is still unknown. Data was gathered from 14 hospitals in the Kyushu area of Japan from December 2013 to March 2017. The median overall survival (mOS) from second-line treatment was contrasted between patients who received second-line chemotherapy (CT group) and those who received the best supportive care (BSC group). Furthermore, the mOS of combination chemotherapy was compared to mono chemotherapy in the CT group. To control possible bias in the selection of treatment, we performed a propensity score-adjusted analysis. A total of 255 patients received GnP or FFX as first-line chemotherapy. There were 156 in the CT group and 77 in the BSC group of these. The CT group had a significantly longer mOS than the BSC group (5.2 vs. 2.6 months; adjusted hazard ratio (HR) 0.38; 95% CI 0.27-0.54). In the CT group, 89 patients received combination chemotherapy while 67 received mono chemotherapy. The mOS did not differ significantly between the combination and mono chemotherapy groups (5.5 vs. 4.8 months; adjusted HR 0.88; 95% CI 0.58-1.33). Among patients with MPC receiving second-line treatment, the CT group had a significantly longer mOS than the BSC group, but combination chemotherapy conferred no improvement in survival compared to mono chemotherapy.

Gemcitabine plus nab-paclitaxel in older patients with metastatic pancreatic cancer: A post-hoc analysis of the real-world data of a multicenter study (the NAPOLEON study).

OBJECTIVES: This study aimed to examine the efficacy and safety of gemcitabine plus nab-paclitaxel (GnP) in older patients with metastatic pancreatic cancer (MPC), especially those ≥75 years old. MATERIALS AND METHODS: This study retrospectively enrolled 153 patients with MPC who received GnP as first-line chemotherapy. Patients ≥75 years old were allocated to the older group, and those <75 years old were assigned to the non-older group. We compared safety, antitumor efficacy, and survival between the two groups. In the older group, prognostic indicators of survival were also assessed. RESULTS: The pretreatment characteristics of the two groups were not significantly different excluding age, history of malignancy, and C-reactive protein levels. The initial dose and relative dose intensities of GnP were significantly lower in the older group. There were no significant differences in the adverse event and antitumor response rates between the two groups. Median progression-free survival and overall survival were 5.5 and 12.0 months, respectively, in the older group, versus 6.0 and 11.1 months, respectively, in the non-older group. In the older group, a Geriatric Nutrition Risk Index (GNRI) of less than 86 was associated with poor prognosis. CONCLUSION: GnP exhibited acceptable efficacy and safety in patients ≥75 years old with MPC. GNRI might be helpful for identifying older individuals at higher risk of unfavorable outcomes.