Gallbladder neuroendocrine carcinoma (NEC) is a rare gallbladder tumor. The current report is a case of a patient preoperatively diagnosed with gallbladder NEC using somatostatin receptor scintigraphy (SRS). A 63‑year‑old man was admitted to our hospital by a family doctor after abdominal ultrasonography revealed thickened walls of the neck of his gallbladder. At Kagoshima University Hospital, CT and MRI of the abdomen and endoscopic ultrasonography confirmed the thickening of the walls of the neck of the gallbladder. However, it did not resemble a typical gallbladder cancer or tumor, such as a neuroendocrine tumor or malignant lymphoma. Positron emission tomography and SRS showed abnormal accumulation at the tumor site. Endoscopic retrograde cholangiopancreatography was performed, adenocarcinoma was suspected based on intra‑gallbladder bile cytology, and a cholecystectomy with lymphadenectomy was performed. The postoperative pathological diagnosis was small cell NEC (pT3a, N0, M0, stage II). Immunohistochemistry indicated that the gallbladder tumor cells were positive for synaptophysin, chromogranin A, and cluster of differentiation (CD) 56, and negative for somatostatin receptors (SSTR) 2 and 5. Gene expression assays revealed the expression of all SSTR subtypes (SSTR1‑5) in the tumor. Generally, NECs exhibit poor accumulation in SRS, however, the results of the current case suggest that SRS may be useful in the preoperative diagnosis of NEC.
FOLFIRINOX (FFX, a combination of oxaliplatin, irinotecan, fluorouracil, and leucovorin) and gemcitabine plus nab-paclitaxel (GnP) have been used as standard, first-line treatments for advanced pancreatic cancer. However, no study has compared the efficacy of the 2 regimens. This study retrospectively compared the efficacy and safety of the 2 regimens in patients with locally advanced pancreatic cancer.We reviewed the records of patients with locally advanced pancreatic cancer who started FFX or GnP as first-line chemotherapy as part of a multicenter retrospective study in patients with unresectable pancreatic cancer treated with FFX or GnP (NAPOLEON study).Sixteen of the 63 patients were treated with FFX, and the other 47 patients were treated with GnP between December 2013 and March 2017. There were no significant differences in median overall survival rate between the GnP (15.5 months) and FFX (14.3 months, P = 0.60) groups or median progression-free survival rate between the GnP (8.8 months) and FFX (8.1 months, P = 0.51) groups. Both treatments were generally well tolerated, although anorexia was more severe in the FFX group than in the GnP group.The effects of FFX and GnP were similar but resulted in different toxicities, which could guide agent choice.
Abstract The relationship between nanoliposomal irinotecan/fluorouracil/leucovorin (NFF) treatment outcomes and neutropenia in patients with pancreatic cancer has not been thoroughly examined. Thus, we conducted a retrospective analysis of data from patients with pancreatic cancer who were treated with NFF to investigate this relationship. Neutropenia was assessed according to the Common Terminology Criteria for Adverse Events across three cutoffs: A (grade 0 versus grade 1–4), B (grades 0–1 versus 2–4), and C (grades 0–2 versus 3–4). The primary endpoint was overall survival (OS), and the secondary endpoints were overall response rate, progression-free survival (PFS), and relative dose intensity. Of the 161 patients, 93, 8, 22, 30, and 8 patients had neutropenia of grades 0, 1, 2, 3, and 4, respectively. The overall response rates differed significantly at cutoff C ( p = 0.02), with the odds ratio for cutoff C being the highest, followed by cutoffs B and A. Significant differences in OS were observed at cutoffs A (hazard ratio [HR], 0.65; 95% confidence interval [CI], 0.44–0.94; p = 0.02) and B (HR, 0.63; 95% CI, 0.43–0.92, p = 0.02). Similarly, PFS showed significant differences at cutoffs A and B ( p < 0.01). NFF-induced neutropenia can be a useful prognostic factor for patients with pancreatic cancer.
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.
Abstract 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.
Abstract Background: Few standard second-line treatment options have been established yet for the treatment of patients with unresectable pancreatic cancer refractory to first-line gemcitabine plus nab–paclitaxel (GnP) therapy. The aim of this study was to compare the outcomes of treatment with nanoliposomal irinotecan + 5-fluorouracil/folinic acid (Nal-IRI + 5-FU/LV), S-1, and FOLFIRINOX as second-line regimens in unresectable pancreatic cancer patients previously treated with first-line GnP therapy. Methods: This was a pooled analysis of two multicenter retrospective studies; the NAPOLEON-1 study, in which unresectable pancreatic cancer patients who had received FOLFIRINOX or GnP as first-line treatment were enrolled, and the NAPOLEON-1 study (retrospective part), in which unresectable pancreatic cancer patients who had received Nal-IRI + 5-FU/LV as second-line treatment were enrolled. The treatment efficacies of the second-line regimens were evaluated by determination of the overall survival (OS) and progression-free survival (PFS) of the patients. Results: Data of a total of 318 patients who had received Nal-IRI + 5-FU/LV (n = 102), S-1 (n = 57), or FOLFIRINOX (n = 14) as second-line treatment were included in this analysis. The median OS in the Nal-IRI + 5-FU/LV group was 9.08 months, while it was significantly worse, at 4.90 months (P = 0.002), in the S-1 group. The median OS in the FOLFIRINOX group was 4.77 months (P = 0.484), and the difference between FOLFIRINOX and Nal-IRI + 5-FU/LV was not statistically significant. Subgroup analyses revealed that in most subgroups, the median OS was better in the patients treated with Nal-IRI + 5-FU/LV than in those treated with S-1. However, a statistical interaction was observed between the treatment regimen and serum Alb < 3.5 g/dL (P = 0.042) and serum CRP ≥ 0.3 mg/dL (P = 0.006). In terms of the PFS, the median PFS was 2.93 months in the Nal-IRI + 5-FU/LV group and significantly worse, at 2.53 months (P = 0.024), in the S-1 group; the FOLFIRINOX group showed a comparable median PFS of 3.04 months (P = 0.948) to that in the Nal-IRI + 5-FU/LV group. Multivariate analysis identified the serum CRP, serum CA19-9, duration of first-line GnP therapy, and use (yes/no) of S-1 for second-line treatment as independent predictors of the OS. Conclusions: Second-line Nal-IRI + 5-FU/LV therapy yielded a more favorable OS than second-line S-1 therapy, however, it is still important to consider the patient background characteristics while selecting the most appropriate treatment.
