Background: There is no established second-line treatment after failure of gemcitabine plus nab-paclitaxel (GnP) therapy for metastatic pancreatic cancer (MPC). The purpose of this study was to evaluate the efficacy and tolerability of the modified FOLFIRINOX (mFFX) as a second-line therapy for MPC and to investigate prognostic factors for survival. Methods: From 2015 to 2019, we retrospectively reviewed the medical records of consecutive patients receiving mFFX for MPC after failure of GnP therapy. Patients were treated every 2 weeks with mFFX (intravenous oxaliplatin 85 mg/m 2 , intravenous irinotecan 150 mg/m 2 , and continuous infusion of 5-fluorouracil 2400 mg/m 2 for 46 h without bolus infusion). Results: In total, 104 patients received mFFX. The median overall survival (OS) was 7.0 months (95% confidence interval [CI]: 6.2-9.8) and the progression-free survival (PFS) 3.9 months (95% CI 2.8-5.0). The objective response rate was 10.6% and the disease control rate 56.7%. The median relative dose intensities of oxaliplatin, irinotecan, and infusional 5-FU were 80.0% (range 21.5-100%), 77.2% (range 38.1-100%), and 85.9% (range 36.9-100%), respectively. Grade 3-4 toxicities were reported in 57 patients (54.8%), including neutropenia, leukopenia, anemia, febrile neutropenia, and peripheral sensory neuropathy. Glasgow prognostic score and carcinoembryonic antigen level were independently associated with survival. Our prognostic model using these parameters could classify the patients into good (n = 38), intermediate (n = 47), and poor (n = 19) prognostic groups. The median OS and PFS time was 14.7 (95% CI 7.6-16.3) and 7.6 months (95% CI 4.1-10.5) for the good prognostic factors, 6.5 (95% CI 5.5-10.0) and 3.6 months (95% CI 2.7-4.8) for the intermediate prognostic factors and 5.0 (95% CI 2.9-6.6) and 1.7 months (95% CI 0.9-4.3) for the poor prognostic factors, respectively.

No abstract

Background There is no established second-line treatment after failure of gemcitabine plus nab-paclitaxel (GnP) therapy for metastatic pancreatic cancer (MPC). This study aimed to evaluate the efficacy and tolerability of the modified FOLFIRINOX (mFFX) as a second-line therapy for MPC and investigate prognostic factors for survival. Methods From 2015–2019, we retrospectively reviewed the medical records of patients receiving mFFX for MPC after failure of GnP therapy. Patients were treated every 2 weeks with mFFX (intravenous oxaliplatin 85 mg/m 2 , intravenous irinotecan 150 mg/m 2 , and continuous infusion of 5-fluorouracil 2,400 mg/m 2 for 46 hours without bolus infusion) until disease progression, patient refusal, or unacceptable toxicity. Results In total, 104 patients received mFFX. The median overall survival (OS) was 7.0 months (95% confidence interval [CI]: 6.2-9.8) and the progression-free survival (PFS) 3.9 months (95% CI 2.8-5.0). The objective response rate was 10.6% and the disease control rate 56.7%. The median relative dose intensities of oxaliplatin, irinotecan, and infusional 5-FU were 80.0% (range 21.5-100%), 77.2% (range 38.1-100%), and 85.9% (range 36.9-100%), respectively. Grade 3-4 toxicities were reported in 57 patients (54.8%), including neutropenia, leukopenia, anemia, febrile neutropenia, and peripheral sensory neuropathy. Glasgow prognostic score and carcinoembryonic antigen level were independently associated with survival. Our prognostic model using these parameters could classify the patients into good (n = 38), intermediate (n = 47), and poor (n = 19) prognostic groups. The median OS and PFS time was 14.7 (95% CI 7.6-16.3) and 7.6 months (95% CI 4.1-10.5) for the good prognostic factors, 6.5 (95% CI 5.5-10.0) and 3.6 months (95% CI 2.7-4.8) for the intermediate prognostic factors and 5.0 (95% CI 2.9-6.6) and 1.7 months (95% CI 0.9-4.3) for the poor prognostic factors, respectively. Conclusions The mFFX showed to be a tolerable second-line treatment for MPC after GnP failure. Our prognostic model might be useful for deciding whether mFFX is indicated in this setting.

Objectives: To compare the treatment outcomes of gemcitabine with nab-paclitaxel (GnP) and modified FOLFIRINOX (mFFX; a combination of fluorouracil, leucovorin, irinotecan, and oxaliplatin) for metastatic pancreatic cancer. Methods:We retrospectively analyzed consecutive patients with metastatic or recurrent pancreatic cancer treated with GnP or mFFX as the first-line chemotherapy between March 2014 and December 2019 in our hospital. Treatment outcomes were compared using propensity score matching to adjust for age, sex, performance status, carcinoembryonic antigen levels, carbohydrate antigen 19-9 levels, and disease status (metastatic or recurrent).Results: Five hundred sixty-eight patients were included (GnP/mFFX, 456/112). After propensity score matching, 218 patients were extracted. The median age was around 61 years, and the proportion of performance status 0 was approximately 90%. The median overall survival values were 14.6 and 15.5 months (P = 0.45), and the median progression-free survival was 7.4 months (P = 0.53) for GnP and mFFX, respectively. The disease control rates were higher in the GnP group (82.6% vs 67.9%, P = 0.02). In nonhematologic adverse events, grade 3/4 anorexia and diarrhea occurred significantly more frequently in the mFFX group.Conclusions: Gemcitabine with nab-paclitaxel had a higher disease control rate and lower rates of severe anorexia and diarrhea in our propensity-matched population.

Neuroendocrine neoplasms (NENs), which are characterized by neuroendocrine differentiation, can arise in various organs. NENs have been divided into well-differentiated neuroendocrine tumors (NETs) and poorly differentiated neuroendocrine carcinomas (NECs) based on morphological differentiation, each of which has a distinct etiology, molecular profile, and clinicopathological features. While the majority of NECs originate in the pulmonary organs, extrapulmonary NECs occur most predominantly in the gastro-entero-pancreatic (GEP) system. Although platinum-based chemotherapy is the main therapeutic option for recurrent or metastatic GEP-NEC patients, the clinical benefits are limited and associated with a poor prognosis, indicating the clinically urgent need for effective therapeutic agents. The clinical development of molecular-targeted therapies has been hampered due to the rarity of GEP-NECs and the paucity of knowledge on their biology. In this review, we summarize the biology, current treatments, and molecular profiles of GEP-NECs based on the findings of pivotal comprehensive molecular analyses; we also highlight potent therapeutic targets for future precision medicine based on the most recent results of clinical trials.