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Background: Fluorouracil, leucovorin (5FU/LV), and nanoliposomal-irinotecan (nal-IRI) combination therapy has been established as the second-line treatment for advanced pancreatic ductal adenocarcinoma. Oxaliplatin with 5FU/LV (FOLFOX) is often used as a subsequent treatment, although its efficacy and safety are yet to be fully elucidated. We aimed to evaluate the efficacy and safety of FOLFOX as a third- or later-line treatment for patients with advanced pancreatic ductal adenocarcinoma. Methods: We conducted a single-centre, retrospective study that enrolled 43 patients who received FOLFOX after failure of gemcitabine-based regimen followed by 5FU/LV + nal-IRI therapy between October 2020 and January 2022. FOLFOX therapy consisted of oxaliplatin (85 mg/m2), levo-leucovorin calcium (200 mg/m2) and 5-FU (2400 mg/m2) every 2 weeks per cycle. Overall survival, progression-free survival, objective response, and adverse events were evaluated. Results: At the median follow-up time of 3.9 months in all patients, the median overall survival and progression-free survival were 3.9 months (95% confidence interval [CI], 3.1–4.8) and 1.3 months (95% CI, 1.0–1.5), respectively. Response and disease control rates were 0 and 25.6%, respectively. The most common adverse event was anaemia in all grades followed by anorexia; the incidence of anorexia and grades 3 and 4 was 21 and 4.7%, respectively. Notably, grades 3–4 peripheral sensory neuropathy was not observed. Multivariable analysis revealed that a C-reactive protein (CRP) level of > 1.0 mg/dL was a poor prognostic factor for both progression-free survival and overall survival: hazard ratios were 2.037 (95% CI, 1.010–4.107; p = 0.047) and 2.471 (95% CI, 1.063–5.745; p = 0.036), respectively. Conclusion: FOLFOX as a subsequent treatment after failure of second-line treatment with 5FU/LV + nal-IRI is tolerable, although its efficacy is limited, particularly in patients with high CRP levels. [ABSTRACT FROM AUTHOR]

Background: In the NAPOLI‐1 phase 3 trial, liposomal irinotecan (nal‐IRI) +5‐fluorouracil/leucovorin (5‐FU/LV) significantly increased mPFS versus 5‐FU/LV (3.1 vs. 1.5 months [unstratified HR = 0.56, p = 0.0001]) in patients with mPAC that progressed on prior gemcitabine‐based therapy. This randomized phase 2 trial evaluated nal‐IRI+5‐FU/LV tolerability (Part 1), safety, and efficacy (Part 2; outcomes reported here) in Japanese patients with mPAC that progressed on gemcitabine‐based therapy. Methods: Patients were randomized 1:1 and stratified by KPS (70 and 80 vs. ≥90) and baseline albumin (≥4.0 g/dl vs. <4.0 g/dl). Primary endpoint was PFS; secondary endpoints were ORR, DCR, OS, TTF, CA19‐9 response, and QoL. The ITT population comprised all randomized patients. Results: Patient characteristics differed between nal‐IRI+5‐FU/LV (n = 40) and 5‐FU/LV (n = 39) arms, including baseline hepatic lesions (63% vs. 51%), stage IV disease at diagnosis (78% vs. 51%), and post‐study anticancer therapy (55% vs. 72%). Investigator‐assessed mPFS increase with nal‐IRI+5‐FU/LV was clinically meaningful and statistically significant versus 5‐FU/LV (2.7 vs. 1.5 months, HR = 0.60). Independently assessed mPFS showed similar trends (1.7 vs. 1.6 months, HR = 0.79). mOS was 6.3 months with nal‐IRI+5‐FU/LV and not reached with 5‐FU/LV. ORR increased significantly with nal‐IRI+5‐FU/LV versus 5‐FU/LV (18% vs. 0, rate difference 17.5). Commonly reported grade ≥3 treatment‐emergent AEs were decreased neutrophil count (37% vs. 3%), decreased white blood cell count (20% vs. 0), and diarrhea (17% vs. 3%). Conclusions: In conclusion, clinically meaningful and statistically significant gains in investigator‐assessed PFS and ORR were observed with nal‐IRI+5‐FU/LV versus 5‐FU/LV in Japanese patients, with no new or unexpected safety signals. (Clinicaltrials.gov ID: NCT02697058). [ABSTRACT FROM AUTHOR]

The prognosis of patients with pancreatic cancer continues to remain dismal, even though numerous trials have been conducted to establish more effective therapies in Japan and throughout the world. Recent advances in treatment have been characterized by the use of novel combinations of conventional cytotoxic chemotherapies. Especially in Japan, S-1 has become one of the most widely used cytotoxic agents for the treatment of pancreatic cancer, after clinical evidence was established of the survival benefit offered by this drug for patients with resectable or unresectable pancreatic cancer. Unfortunately, with the exception of erlotinib, no targeted treatment strategies have been approved for pancreatic cancer. However, following an increase in interest in drug development in recent years, proactive attempts have been made to develop new therapeutic strategies, including neoadjuvant chemotherapy for patients with resectable or borderline resectable pancreatic cancer, multi-agent combination chemotherapy for patients with advanced pancreatic cancer, and therapies with new targeted agents or immuno-oncologic agents for patients with pancreatic cancer bearing specific gene mutations. [ABSTRACT FROM AUTHOR]

Abstract: While surgery currently remains the only potentially curative treatment available for pancreatic cancer, only 20% to 30% of patients have resectable disease at diagnosis. Recently, with the introduction of intensive chemotherapy regimens such as oxaliplatin, irinotecan, fluorouracil plus leucovorin (FOLFIRINOX) and gemcitabine plus nab‐paclitaxel, for the treatment of unresectable pancreatic cancer, the antitumor activity and overall survival in patients with pancreatic cancer have dramatically improved. These advances in intensive chemotherapy have led to the possibility of conversion of unresectable disease to resectable disease, and it has been reported that more than 20% of pancreatic cancer patients with unresectable locally advanced disease at diagnosis undergo successful conversion surgery after FOLFIRINOX therapy. In metastatic pancreatic cancer, resection for the primary lesion of pancreatic cancer may show some benefits for some patients with complete resolution of metastases by chemotherapy. Furthermore, surgical resection in some patients with only a few metastases, so‐called oligometastases, have also been reported. Conversion surgery is becoming increasingly possible with the introduction of intensive chemotherapies, however, the actual clinical benefits of resection in such cases has not yet been sufficiently investigated. The long‐term safety, feasibility and outcomes still need to be investigated in well‐designed, multi‐institutional studies on a large number of patients. [ABSTRACT FROM AUTHOR]

Background Pancreatic cancer is one of the most devastating diseases with an extremely high mortality. Medical organizations and scientific societies have published a number of guidelines to address active treatment of pancreatic cancer. The aim of this consensus review was to identify where there is agreement or disagreement among the existing guidelines and to help define the gaps for future studies. Methods A panel of expert pancreatologists gathered at the 46th European Pancreatic Club Meeting combined with the 18th International Association of Pancreatology Meeting and collaborated on critical reviews of eight English language guidelines for the clinical management of pancreatic cancer. Clinical questions (CQs) of interest were proposed by specialists in each of nine areas. The recommendations for the CQs in existing guidelines, as well as the evidence on which these were based, were reviewed and compared. The evidence was graded as sufficient, mediocre or poor/absent. Results Only 4 of the 36 CQs, had sufficient evidence for agreement. There was also agreement in five additional CQs despite the lack of sufficient evidence. In 22 CQs, there was disagreement regardless of the presence or absence of evidence. There were five CQs that were not addressed adequately by existing guidelines. Conclusion The existing guidelines provide both evidence- and consensus-based recommendations. There is also considerable disagreement about the recommendations in part due to the lack of high level evidence. Improving the clinical management of patients with pancreatic cancer, will require continuing efforts to undertake research that will provide sufficient evidence to allow agreement. [ABSTRACT FROM AUTHOR]

The FOLFIRINOX combination of chemotherapy drugs had not been fully evaluated for Japanese pancreatic cancer patients. Therefore, we carried out a phase II study to examine the efficacy and safety of FOLFIRINOX in chemotherapy-naïve Japanese patients with metastatic pancreatic cancer. FOLFIRINOX (i.v. infusion of 85 mg/m2 oxaliplatin, 180 mg/m2 irinotecan, and 200 mg/m2 l-leucovorin, followed by a bolus of 400 mg/m2 fluorouracil and a 46-h continuous infusion of 2400 mg/m2 fluorouracil) was given every 2 weeks. The primary endpoint was the response rate. The 36 enrolled patients received a median of eight (range, 1-25) treatment cycles. The response rate was 38.9% (95% confidence interval [ CI], 23.1-56.5); median overall survival, 10.7 months (95% CI, 6.9-13.2); and median progression-free survival, 5.6 months (95% CI, 3.0-7.8). Major grade 3 or 4 toxicities included neutropenia (77.8%), febrile neutropenia (22.2%), thrombocytopenia (11.1%), anemia (11.1%), anorexia (11.1%), diarrhea (8.3%), nausea (8.3%), elevated alanine aminotransferase levels (8.3%), and peripheral sensory neuropathy (5.6%). Febrile neutropenia occurred only during the first cycle. There were no treatment-related deaths. FOLFIRINOX can be a standard regimen showing favorable efficacy and acceptable toxicity profile in chemotherapy-naïve Japanese patients with metastatic pancreatic cancer. [ABSTRACT FROM AUTHOR]

The aim of this study was to investigate the feasibility and efficacy of induction chemotherapy with gemcitabine and S-1 followed by chemoradiotherapy for locally advanced pancreatic cancer. Patients with locally advanced unresectable pancreatic cancer received four cycles of induction chemotherapy consisting of 30-min intravenous infusions of gemcitabine 1,000 mg/m2 on days 1 and 8 and oral S-1 40 mg/m2 twice daily on days 1–14 of a 21-day cycle. Those without disease progression received chemoradiotherapy of 30 Gy in ten fractions with 250 mg/m2 of gemcitabine on days 1 and 8. A total of 20 patients were treated. Median follow-up time was 431 days (range 133–1,014 days). Four cycles of induction chemotherapy were completed in 18 patients, and 16 patients received chemoradiotherapy, which was completed without delay in all. Grade 3–4 toxicities associated with induction chemotherapy were neutropenia (50%); anemia (20%); thrombocytopenia (10%); febrile neutropenia (5%); nausea (10%); anorexia (10%); and vomiting, fatigue, dehydration, stomatitis, and rash (5%). Grade 3–4 toxicities among those receiving chemoradiotherapy were neutropenia (13%) and anemia (6%). Median progression-free survival was 8.1 months. Median overall survival was 14.4 months, with a 1-year survival rate of 54.2%. The regimen of induction chemotherapy with gemcitabine and S-1 followed by chemoradiotherapy used in the present study demonstrated promising activity in locally advanced pancreatic cancer. Further consideration of radiation schedule and duration of induction chemotherapy is required to enhance the efficacy of this strategy. [ABSTRACT FROM AUTHOR]

Background and Objective: Gemcitabine (2′,2′-difluorodeoxycytidine) is an anticancer drug, which is effective against solid tumours, including non-small-cell lung cancer and pancreatic cancer. After gemcitabine is transported into cells by equilibrative and concentrative nucleoside transporters, it is phosphorylated by deoxycytidine kinase (DCK) and further phosphorylated to its active diphosphorylated and triphosphorylated forms. Gemcitabine is rapidly metabolized by cytidine deaminase (CDA) to an inactive metabolite, 2′,2′-difluorodeoxyuridine (dFdU), which is excreted into the urine. Toxicities of gemcitabine are generally mild, but unpredictable severe toxicities such as myelosuppression and interstitial pneumonia are occasionally encountered. The aim of this study was to determine the factors, including genetic polymorphisms of CDA, DCK and solute carrier family 29A1 (SLC29A1 [hENT1]), that alter the pharmacokinetics of gemcitabine in Japanese cancer patients. Patients and Methods: 250 Japanese cancer patients who received 30-minute intravenous infusions of gemcitabine at 800 or 1000 mg/m2 in the period between September 2002 and July 2004 were recruited for this study. However, four patients were excluded from the final model built in this study because they showed bimodal concentration-time curves. Two patients who experienced gemcitabine-derived life-threatening toxicities in October 2006 and January 2008 were added to this analysis. One of these patients received 30-minute intravenous infusions of gemcitabine at 454 mg/m2 instead of the usual dose (1000 mg/m2). Plasma concentrations of gemcitabine and dFdU were measured by high-performance liquid chromatography-photodiode array/mass spectrometry. In total, 1973 and 1975 plasma concentrations of gemcitabine and dFdU, respectively, were used to build population pharmacokinetic models using nonlinear mixed-effects modelling software (NONMEM® version V level 1.1). Results and Discussion: Two-compartment models fitted well to plasma concentration-time curves for both gemcitabine and dFdU. Major contributing factors for gemcitabine clearance were genetic polymorphisms of CDA, including homozygous CDA*3 [208G>A (Ala70Thr)] (64% decrease), heterozygous *3 (17% decrease) and CDA -31delC (an approximate 7% increase per deletion), which has a strong association with CDA*2 [79A>C (Lys27Gln)], and coadministered S-1, an oral, multicomponent anti-cancer drug mixture consisting of tegafur, gimeracil and oteracil (an approximate 19% increase). The estimated contribution of homozygous CDA*3 to gemcitabine clearance provides an explanation for the life-threatening severe adverse reactions, including grade 4 neutropenia observed in three Japanese patients with homozygous CDA*3. Genetic polymorphisms of DCK and SLC29A1 (hENT1) had no significant correlation with gemcitabine pharmacokinetic parameters. Aging and increased serum creatinine levels correlated with decreased dFdU clearance. Conclusion: A population pharmacokinetic model that included CDA genotypes as a covariate for gemcitabine and dFdU in Japanese cancer patients was successfully constructed. The model confirms the clinical importance of the CDA*3 genotype. [ABSTRACT FROM AUTHOR]

Gemcitabine monotherapy or gemcitabine-containing combination chemotherapy is the standard first-line therapy for advanced pancreatic cancer. After disease progression, there is no standard regimen available. In a previous phase II trial, S-1 has been reported to show considerable efficacy, achieving a response rate of 37.5% in chemo-naïve patients with pancreatic cancer. This study evaluated the efficacy and toxicity of S-1 in patients with gemcitabine-refractory metastatic pancreatic cancer. Eligibility criteria were histologically proven pancreatic adenocarcinoma with confirmation of progressive disease while receiving gemcitabine-based first-line chemotherapy, 20–74 years of age, Karnofsky performance status of 80–100 points, with measurable metastatic lesions, adequate hematological, renal and liver functions, and written informed consent. S-1 was administered orally at 40 mg/m2 twice daily for 28 days with a rest period of 14 days as one course. Administration was repeated until the appearance of disease progression or unacceptable toxicity. The primary endpoint of this study was an objective response, and secondary endpoints included toxicity, progression-free survival (PFS) and overall survival, as well as clinical benefit response in symptomatic patients. Forty patients from two institutions were enrolled between September 2004 and November 2005. The most common adverse reactions were fatigue and anorexia, although most of those adverse reactions were tolerable and reversible. One patient developed grade 3 pneumonitis without neutropenia and recovered with appropriate antibiotic treatment. Although no complete response was seen, partial response was obtained in six patients (15, 95% confidence interval, 3.9–26%). Stable disease was noted in 17 patients (43%), and progressive disease in 15 patients (38%). Out of 19 evaluable patients, a clinical benefit response was observed in four patients (21%). The median PFS was 2.0 months, and the median survival time was 4.5 months with a 1-year survival rate of 14.1%. S-1 as monotherapy had marginal anti-tumor activity with tolerable toxicity in patients with gemcitabine refractory metastatic pancreatic cancer. [ABSTRACT FROM AUTHOR]

Objective: The aim of this study was to determine the maximum-tolerated dose and dose-limiting toxicity (DLT) of combination therapy with gemcitabine and S-1 in patients with advanced pancreatic cancer. Methods: Chemotherapy-naive patients with histologically or cytologically proven unresectable or metastatic pancreatic cancer were enrolled. The patients received gemcitabine intravenously over 30 min on days 1 and 8 and S-1 orally twice daily from days 1 to 14. Cycles were repeated every 21 days until disease progression. Patients were scheduled to receive gemcitabine (mg/m2/week) and S-1 (mg/m2/day) at four dose levels: 800/60 (level 1), 1,000/60 (level 2), 1,000/70 (level 3) and 1,000/80 (level 4). Results: Eighteen patients were enrolled in this study. The maximum-tolerated dose was not reached even at the highest dose level (level 4) because only 2 of the 6 patients at this level experienced DLT. The DLTs were neutropenia and rash. Six (33%) of the 18 patients achieved a partial response and median overall survival time was 7.6 months. Conclusions: Combination chemotherapy with gemcitabine and S-1 was well tolerated and showed good antitumor activity in the treatment of pancreatic cancer. We recommend a gemcitabine dose of 1,000 mg/m2/week and an S-1 dose of 80 mg/m2/day in further studies with this schedule. Copyright © 2005 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Systemic chemotherapy plays an important role in the treatment of pancreatic cancer, to improve the survival of patients with pancreatic cancer. Unresectable pancreatic cancer can be classified into three categories: metastatic, locally advanced, and hereditary pancreatic cancers. Furthermore, the second-line chemotherapy is required to prolong the survival. The combined regimens of oxaliplatin, irinotecan, fluorouracil and leucovorin (FOLFIRINOX) and gemcitabine plus nab-paclitaxel (GEM plus nab-PTX) have been recognized as the standard of care for advanced pancreatic cancer. However, the consensus of selection of the first-line chemotherapy still remains. Randomized controlled trials (RCTs) between FOLFIRINOX and GEM plus nab-PTX are ongoing for locally advanced and metastatic disease in Japan, respectively. Hereditary pancreatic cancer, especially associated with BRCA mutations, is responsive to platinum-containing regimens and/or poly (ADP-ribose) polymerase (PARP) inhibitors. It is becoming more important to examine the presence/absence of BRCA mutations to select the appropriate treatment strategy for individual patients. Although some S-1-based regimens have been investigated in the second-line treatment after GEM-based chemotherapy in Japan, no regime demonstrated survival benefit. Nanoliposomal irinotecan (nal-IRI) plus FF has been established as the standard of care in the second-line treatment in a global phase III trial (NAPOLI-1). A randomized phase II trial comparing FF plus nal-IRI with FF alone was also conducted in Japan to examine the efficacy and safety of the FF plus nal-IRI in Japanese patients. [ABSTRACT FROM AUTHOR]

Background: Long-term survival after resection of metastases from pancreatic ductal adenocarcinoma is rare.Case presentation: A 54-year-old man underwent pancreaticoduodenectomy (PD) for pancreatic ductal adenocarcinoma (PDAC) with UICC staging pT3N1M0 followed by adjuvant chemotherapy with gemcitabine (GEM). Three years after radical resection of the primary tumor, a tiny nodule was found in the lower lobe of the left lung. Despite treatment with GEM, it increased gradually, but no other metastases were found. Eighteen months after the first indication of the nodule, wedge resection was performed. Pathological examination of the nodule indicated a metastatic tumor from PDAC. Pulmonary metastasectomy was again performed for lung oligometastases at 77 and 101 months after PD. The patient has been asymptomatic without tumor recurrence for 4 years since the last pulmonary resection.Conclusions: In PDAC, the treatment strategy for oligometastasis is controversial. However, a few cases of long-term survival after pulmonary metastasectomy for oligometastasis of PDAC have been reported. More such cases need to be studied to address this issue effectively. [ABSTRACT FROM AUTHOR]

This phase 1b trial evaluated the toxicity and efficacy of S-1, irinotecan, and oxaliplatin combination therapy (S-IROX) as first-line chemotherapy in patients with advanced pancreatic cancer (APC). Patients aged 20–75 years with APC and an Eastern Cooperative Oncology Group performance status of 0 or 1 were eligible to receive escalating doses of S-1 (60 or 80 mg m2·day) on days 1–7, fixed doses of oxaliplatin (85 mg/m2) biweekly, and escalating doses of irinotecan (150, 165, or 180 mg/m2) once every 2 weeks. In the dose-escalation cohort, a 3 + 3 design was used to determine the maximum-tolerated dose (MTD) and explore the recommended dose (RD). A dose-expansion cohort was added to further evaluate the safety and efficacy of the combination. This trial was registered at UMIN-CTR (UMIN000012054). Approximately 47 patients were enrolled, of whom 45 were eligible for the analysis. The MTD was not determined, but the RD was determined to be dose level 1 based on a review of data from each level. Among the 45 patients, the ORR was 51.1% [95% confidence interval (CI), 35.8–66.3%]. The median progression-free survival and median overall survival was 6.9 months (95% CI, 5.1–8.8 months) and 15.8 months (95% CI, 9.8–20.8 months), respectively. Common adverse events included neutropenia, elevated liver enzyme levels, diarrhoea, and nausea. The S-IROX regimen showed promising efficacy with manageable toxicities in Japanese patients with APC. A randomised phase 2/3 trial comparing S-IROX, mFOLFIRINOX, and gemcitabine plus nab-paclitaxel is currently ongoing (jRCTs031190009). • Phase 1b trial of S-1, irinotecan, and oxaliplatin in pancreatic cancer. • The RD was S-1 80 mg/m2, irinotecan 150 mg/m2, and oxaliplatin 85 mg/m2. • The ORR was 51.1%, and PFS and OS were better than those of the historical FOLFIRINOX. [ABSTRACT FROM AUTHOR]

Abstract Background In our previous randomised phase 2 study for patients with gemcitabine-refractory advanced pancreatic cancer, S-1 plus leucovorin improved progression-free survival compared with S-1 alone. Here, we evaluated the efficacy of TAS-118 (S-1 plus leucovorin) versus S-1 in overall survival (OS). Patients and methods This randomised, open-label, phase 3 study was conducted at 58 centres in Japan and Korea. Patients with metastatic pancreatic cancer that progressed during first-line gemcitabine-based chemotherapy or recurred during or after post-operative gemcitabine-based adjuvant treatment were randomly assigned (1:1) to receive either S-1 (40–60 mg, twice daily for 4 weeks in a 6-week cycle) or TAS-118 (S-1 40–60 mg plus leucovorin 25 mg, twice daily for 1 week in a 2-week cycle). The primary end-point was OS. Results A total of 603 patients were randomised, and 300 and 301 patients received TAS-118 and S-1, respectively. There was no difference in OS between groups (median OS for TAS-118 versus S-1, 7.6 months versus 7.9 months; hazard ratio [HR], 0.98 [95% confidence interval (CI), 0.82–1.16]; P = 0.756). Progression-free survival was significantly longer with TAS-118 than S-1 (median, 3.9 months versus 2.8 months; HR, 0.80 [95% CI, 0.67–0.95]; P = 0.009). There were interactions between Japan and Korea (P = 0.004) and between unresectable and recurrent disease (P = 0.025) in OS. Incidence, profile and severity of adverse events were similar between groups. Conclusion TAS-118 did not improve OS in patients with gemcitabine-refractory advanced pancreatic cancer compared to S-1. Further studies are needed to find patients who have benefit from adding leucovorin to S-1. Highlights • TAS-118 did not improve overall survival for gemcitabine-refractory advanced pancreatic cancer. • TAS-118 improved progression-free survival compared with S-1 monotherapy. • TAS-118 might be more effective than S-1 in some populations of patients. [ABSTRACT FROM AUTHOR]

Abstract: Background: Secondary depression is common in the clinical oncology setting after pancreatic cancer diagnosis, following which the patients have to face the fact that they have a cancer with an extremely poor prognosis. However, the specific pathophysiology remains unclear. The present study examined the regional cerebral glucose metabolism using F18-fluorodeoxyglucose (F18-FDG) positron emission tomography (PET) in antidepressant-naïve pancreatic cancer patients with a depressive episode after their cancer diagnosis and before their cancer treatment. Methods: Regional cerebral glucose metabolism in pancreatic cancer patients without any antidepressant medication after the cancer diagnosis was measured with F18-FDG PET. A depressive episode after the cancer diagnosis was defined as including major and minor depressive episodes, and was diagnosed using the Diagnostic and Statistical Manual, Fourth Edition (DSM-IV). The prefrontal and limbic regions were the primary regions-of-interest, and an uncorrected value of p <0.005 was used as significant. Results: Six of 21 pancreatic cancer patients were diagnosed as having a depressive episode. Significantly higher glucose metabolism in depressed patients was found in the subgenual anterior cingulate cortex (sACC) (uncorrected p =0.002). Limitations: There was a small number of subjects, and there were no healthy controls. Conclusions: The higher metabolism in the sACC may be associated with the pathophysiology of secondary depressive episodes in patients following pancreatic cancer diagnosis. [Copyright &y& Elsevier]

Background A family and personal history of breast (B), ovarian(O), and pancreatic(P) cancer was reported to be a predictive marker in patients with pancreatic adenocarcinoma (PA) treated with platinum-based chemotherapy. We planned a prospective phase II trial to evaluate the efficacy and safety of platinum-based chemotherapy in this population. Method Eligible patients had chemotherapy-naïve metastatic PA, had one or more of the followings: 1) at least one family history of P/B/O/prostate (PR) cancer in a first-degree relative, 2) at least two family members with history of P/B/O/PR cancer within third-degree relatives, and 3) at least one personal history of B/O/PR cancer.Patient suitable for FOLFIRINOX or gemcitabine plus nab-paclitaxel were ineligible unless patient refuse those regimens. Patients received gemcitabine 1000mg/m2and oxaliplatin 100 mg/m2 every two weeks (GEMOX). The primary endpoint was the one-year survival rate and 44% were desired. The sample size was calculated to be 43 pts, with a one-sided alpha of 5% and a power of 80%. Results A total of 45 pts were enrolled. First 43 pts were included in primary analysis. One-year survival rate was 27.9 [90%CI;17.0-41.3]% and didn't met pre-planned boundary. Response rate was 27.9%. Tendency of prolonged survival was observed in patients with two or more family histories of P/B/O/PR cancer (HR 0.65, 95%CI [0.34-1.23]). Family history or personal history with B/O/PR cancer tended to be associate with better response and prolonged survival. In this study, patient with family history of pancreatic cancer seemed to be associate with poor response. The most common adverse events of grade 3 or higher were neutropenia (36%), leukopenia (27%), thrombocytopenia (23%) and elevated level of ALT (20%). Treatment related death was not observed. Conclusion GEMOX did not show expected efficacy in patients with metastatic PA with family history or personal history of P/B/O/PR cancer. [ABSTRACT FROM AUTHOR]