Treatment Of Advanced Pancreatic Cancer Research Articles

Apartinib in combination with S-1 for the second-line treatment of advanced pancreatic cancer (APC).

TPS781 Background: The prognosis for patients with advanced pancreatic cancer (APC) is extremely dismal. First-line treatment for APC is gemcitabine/5-FU-based chemotherapy with no standard second-line treatment. Anti-angiogenic therapy combined with chemotherapy have showed its effects in improving the outcomes in a variety of cancers. Apatinib is an oral tyrosine kinase inhibitor that selectively targets VEGFR2. Some preclinical studies and several case reports showed the anti-tumor effect of apatinib in pancreatic cancer, but there is no evidence from clinical trial to confirm it. This study aims to evaluate the efficacy and safety of apartinib in combination with S-1 as the second-line therapy for patients with APC. Methods: In this open-label, single-arm, randomized phase II study, we will recruit 30 patients with pathologically proven advanced pancreatic cancer after the failure of first-line chemotherapy. All patients are aged 18-70 years with ECOG PS 0-2 and will receive apatinib at an initial dose of 500mg/d on a continuous basis, and oral S-1 (60mg/d for BSA < 1.25m2, 80mg/d for 1.25<BSA < 1.5m2, and 100mg for BSA >1.5m2, orally) twice a day on days 1-14 of a 21-day cycle. Primary endpoint is PFS. Secondary endpoints include OS, duration of response, ORR and DCR. The safety of apartinib + S-1 will be evaluated by CTCAE v4.0. Translational research will be performed in blood (before and on-treatment): cytokine panel to explore predictive and prognostic biomarkers. Clinical trial information: NCT03662035.

First-line drug selection versus sequential treatment in advanced pancreatic cancer: Does it really matter? Multi-institutional Canadian perspective.

673 Background: Folfirinox (FFX) and Gemcitabine with nab-Paclitaxel (GN) are both proven to be superior to Gemcitabine (G) in the first line treatment (1LTx) for advanced pancreatic cancer (APC). Yet, the optimal 1LTx selection nor sequential Tx (ST) has not been fully established. Therefore, the best choice for 1LTx is a matter of debate often influenced by access to drugs. This analysis was conducted to compare outcomes based on 1Ltx selection and ST in APC. Methods: We assessed patients (pts) with APC who received either FFX or GN as 1LTx during 2010-2019 at three Canadian institutions. As well as the ST used. The main objective was to assess survival. Kaplan method and log-rank test were used for survival curves. Results: This retrospective study included 231 pts; 1LTx included 143 pts on FFX and 88 pts on GN. FFX pts were predominantly male; 89(62.2%) vs 46(52.3%) and slightly younger (median age 62 vs 66) than GN. WHO performance status (PS) of 0 were 38 (28.4%) vs 14 (16.5%) and 1 were 90 (67.2%) vs 65 (76.5%) respectively. There were more grade 3-4 toxicity in FFX vs GN group: GI 55 (38.5%) vs 15 (17%) and hematologic 51 (35.4%) vs 20 (22.7%) respectively. Grade 3-4 neutropenia rates were similar in both regimens. The median PFS of FFX was 5.5 months (95% CI: 5.0-6.7) vs 5.1 (95% CI: 3.8-7.1) with GN (p=0.37). The median OS with FFX was 9.3 months (95% CI: 7.5-11.1) vs 10.2 (95% CI: 6.8-11.3) with GN (p=0.81). There were not statically significant. Table shows Tx frequency across 4LTx. 2LTx and beyond regimens included G, GN, FFX, Capecitabine, Irinotecan liposome plus 5-FU, Irinotecan and clinical trials. Conclusions: Our results revealed that pts who received 1LTx FFX or GN had similar PFS and OS even though 1LTx FFX group was younger with better PS, allowing to continue 2-4LTx more frequently when compare with 1LTx GN group. Therefore, 1LTx selection appear to have more impact in our pts rather than ST, whereas GN is less toxic and seems a preferable 1LTx choice for most pts. FFX could be reserved for young high-performance pts. [Table: see text]

Efficacy and Safety of Pegylated Recombinant Human Granulocyte Stimulating Factor in Secondary Prevention of Albumin Paclitaxel Combined With S-1 in the First-line Treatment of Advanced Pancreatic Cancer

Efficacy and Safety of Pegylated Recombinant Human Granulocyte Stimulating Factor in Secondary Prevention of Albumin Paclitaxel Combined With S-1 in the First-line Treatment of Advanced Pancreatic Cancer

The Efficacy and Safety of K-001 in the Treatment of Advanced Pancreatic Cancer

The Efficacy and Safety of K-001 in the Treatment of Advanced Pancreatic Cancer

Recurrence in Patients Achieving Pathological Complete Response After Neoadjuvant Treatment for Advanced Pancreatic Cancer.

The aim of this study was to characterize the patterns and treatment of disease recurrence in patients achieving a pathological complete response (pCR) following neoadjuvant chemoradiation for advanced pancreatic ductal adenocarcinoma (PDAC). A pCR is an independent predictor for improved survival in PDAC. However, disease recurrence is still observed in these patients. Patients with advanced PDAC who were treated with neoadjuvant therapy and had a pCR were identified between 2009 and 2017. Overall survival (OS) was determined from the initiation of neoadjuvant, disease-free survival (DFS) from the date of surgery, and post-recurrence survival (PRS) from the date of recurrence. Factors associated with recurrence were analyzed using a Cox-regression model. Of 331 patients with borderline resectable or locally advanced PDAC, 30 achieved a pCR following neoadjuvant treatment and pancreatectomy. The median DFS for pCR patients was 29 months and OS 76 months. Recurrence was observed in 14 patients. No clinicopathologic or treatment characteristics were associated with survival. The median PRS following recurrence was 25 months. Treatment following recurrence included chemotherapy, radiation or ablation, and surgical resection. Hepatectomy or completion pancreatectomy was accomplished in 2 patients that remain alive 13 and 62 months, respectively, following metastasectomy. A pCR following neoadjuvant therapy in patients with advanced PDAC is associated with remarkable survival, although recurrence occurs in about half of patients. Nevertheless, patients with pCR and recurrence respond well to treatment and survival remains encouraging. Advanced molecular characterization and longitudinal liquid biopsy may offer additional assistance with understanding tumor biologic behavior after achieving a pCR.

Erythrocyte-encapsulated asparaginase (eryaspase) combined with chemotherapy in second-line treatment of advanced pancreatic cancer: An open-label, randomized Phase IIb trial

PurposeThis Phase IIb (NCT02195180) open-label study evaluated erythrocyte-encapsulated asparaginase (eryaspase) in combination with chemotherapy in second-line advanced pancreatic adenocarcinoma. MethodsEligible patients were randomized 2:1 to either eryaspase in combination with gemcitabine or mFOLFOX6 (eryaspase arm), or to gemcitabine or mFOLFOX6 alone (control arm). Co-primary endpoints were overall survival (OS) and progression-free survival (PFS) in patients with low asparagine synthetase (ASNS) expression. Secondary endpoints included OS and PFS in the entire population. Results141 patients were randomized (eryaspase arm, n = 95; control arm, n = 46). Median OS and PFS in patients with low ASNS expression were 6.2 months (95% CI, 5.1–8.8) in the eryaspase arm versus 4.9 months (3.1–7.1) in the control arm (HR, 0.63; 95% CI, 0.39–1.01; P = 0.056) and 2.0 months (95% CI, 1.8–3.4) in the eryaspase arm versus 1.8 months (1.4–3.8) in the control arm (HR, 0.67; 95% CI, 0.40–1.12; P = 0.127), respectively. In the entire population, median OS and PFS for the eryaspase arm versus control were 6.0 months versus 4.4 months (HR, 0.60; P = 0.008) and 2.0 months versus 1.6 months (HR, 0.56; 95% CI, 0.37–0.84; P = 0.005), respectively. The combination of eryaspase and chemotherapy was well tolerated. The most frequent Grade 3/4 adverse events in the eryaspase arm (n = 93) were gamma-glutamyltransferase increase (16 [17.2%]), neutropenia (12 [12.9%]), and physical health deterioration (12 [12.9%]). ConclusionEryaspase in combination with chemotherapy is associated with improvements in OS and PFS, irrespective of ASNS expression in second-line advanced pancreatic adenocarcinoma. A Phase III trial is underway.

181P - The emerging role of third-line gemcitabine plus nab-paclitaxel in advanced pancreatic adenocarcinoma

BackgroundThere are no standardised, recognised regimens for third line treatment of advanced pancreatic cancer, with most clinicians using best supportive care in this scenario. Gemcitabine plus nab-paclitaxel and FOLFIRINOX are non-cross resistant regimens. This generates the hypothesis that patients who responded well in the first line setting to gemcitabine and nab-paclitaxel could respond again if rechallenged in the third line setting, after second line FOLFIRINOX. MethodsA retrospective analysis was conducted via an electronic database from two of our institutions, of locally advanced or metastatic pancreatic adenocarcinoma patients who were treated with gemcitabine plus nab-paclitaxel both as a first line and third line chemotherapy regimen between January 2013 and July 2019. All patients had an ECOG performance status of 2 or less. Overall survival (OS) was estimated by the Kaplan-Meier method. ResultsWe identified 30 patients in our analysis. 63% of the patients were female, with the median age of all patients at diagnosis being 67 (range, 38 – 82). 60% of the studied patients had locally advanced disease at diagnosis. Median OS from diagnosis was 39.0 months (95% CI, 34.0 – 66.0). Median OS from third-line re-initiation of gemcitabine plus nab-paclitaxel was 29.0 months (95% CI, 9.0 – 36.0). ConclusionsPatient who maintain a good performance status after second line treatment present a management dilemma, as these patients are often reluctant to accept best supportive care when they feel well enough to tolerate another line of chemotherapy. The median OS (29 months) and age (67) is surprising, but probably represents the selection bias of patients who retain sufficient performance status to undergo third line therapy. Patients who have receive first line gemcitabine plus nab-paclitaxel, and second line FOLFIRINOX whilst maintaining good performance status, should be considered for re-treatment with gemcitabine plus nab-paclitaxel, as evidenced by our data from two of our institutions. Phase III studies would be highly beneficial to further investigate this as a potential standard of care for third-line treatment in this group. Legal entity responsible for the studySt John of God Hospital Subiaco. FundingHas not received any funding. DisclosureAll authors have declared no conflicts of interest.

705P - Multicenter retrospective study of gemcitabine plus nab-paclitaxel for elderly patients with advanced pancreatic cancer

BackgroundAlthough gemcitabine plus nab–paclitaxel (GnP) is a standard treatment for advanced pancreatic cancer as the result of phase III trial ((MPACT), its therapeutic benefit for elderly patients is unclear. This study aimed to assess the effectiveness and safety of GnP for these patients. MethodsWe retrospectively enrolled patients aged>=75 years in whom GnP was initiated as first–line treatment for advanced pancreatic cancer between December 2014 and December 2016. Overall survival and progression–free survival according to disease status were calculated using Kaplan–Meier method. Objective response was estimated according to RECISTv1.1. Adverse events were evaluated according to based on the Common Terminology Criteria of Adverse Events version4.0. The incidence of adverse events and early discontinuation (i.e., treatment discontinuation due to adverse events within 2 months from initiation) was compared via Fishers’ exact test for univariate analysis and via logistic regression model with step wise method for multivariate analysis. ResultsThe cohort comprised 116 selected patients with a median age of 77 years (range: 75–84 years). Within a median follow-up of 13 months, the median overall survival and progression-free survival of locally advanced cancer patients were 21.8 and 12.1 months, respectively. In patients with metastasis, these were 13.3 and 5.9 months. The response rate was 31% and the disease control rate was 81%. Within the first 2 months of treatment, grade 4 hematological and grade 3–4 non-hematological toxicities were observed in 10 and 23 patients, respectively. Early treatment discontinuation of GnP occurred in 12 patients, and the associated risk factors were age>=80 years [odds ratio (OR), 9.43; 95% confidence interval (CI), 2.25–39.60] and serum albumin <35g/L (OR, 5.12; 95% CI, 1.11–23.61). ConclusionsGnP in selected patients aged>=75 years showed acceptable toxicities and comparable effectiveness to that in the previous studies of the non-elderly population, but patients aged>=80 years and with serum albumin <35 d/L should be carefully assessed for treatment eligibility. Legal entity responsible for the studySatoshi Kobayashi. FundingHas not received any funding. DisclosureM. Ozaka: Honoraria (self): Taiho Pharmaceutical; Honoraria (self): Pfizer; Honoraria (self): Novartis Pharma; Honoraria (self): Bayer Yakuhin; Honoraria (self): Yakult Honsha; Honoraria (self): Eisai; Honoraria (self): EA Pharma. S. Kobayashi: Honoraria (self), Research grant / Funding (institution): Taiho pharmaceutical; Honoraria (self): Boston Scientific; Honoraria (self), Speaker Bureau / Expert testimony: Kyowa Hakko Kirin; Honoraria (self), Research grant / Funding (institution): Daiichi Sankyo; Honoraria (self), Speaker Bureau / Expert testimony: Bayer Yakuhin; Honoraria (self): Teijin Pharma; Honoraria (self), Research grant / Funding (institution): Eisai; Research grant / Funding (institution): Eli Lilly; Research grant / Funding (institution): Dainippon Sumitomo Pharma; Research grant / Funding (institution): Chugai Pharma; Research grant / Funding (institution): Yakult Honsha; Research grant / Funding (institution): AstraZeneca; Research grant / Funding (institution): Takara Bio; Research grant / Funding (institution): Merck Serono; Research grant / Funding (institution): Ono Pharmaceutical; Research grant / Funding (institution): MSD Oncology; Research grant / Funding (institution): Boehringer Ingelheim; Research grant / Funding (institution): Beigene; Research grant / Funding (institution): Takeda. M. Ikeda: Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution): Novartis Pharma; Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution): Bayer Yakuhin; Honoraria (self), Research grant / Funding (institution): Bristol-Myers Squibb; Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution): Eisai; Honoraria (self), Research grant / Funding (institution): Taiho Pharmaceutical; Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution): Eli Lilly; Honoraria (self), Research grant / Funding (institution): Yakult; Honoraria (self): Otsuka Pharmaceutical; Honoraria (self): Nobel Pharma; Honoraria (self), Advisory / Consultancy: Daiichi-Sankyo; Honoraria (self): Sumitomo Dainippon Pharma; Honoraria (self): Teijin Pharma; Honoraria (self): EA Pharma; Honoraria (self): Kaken Pharmaceutical; Advisory / Consultancy: Shire; Advisory / Consultancy: MSD; Advisory / Consultancy, Research grant / Funding (institution): ASLAN Pharmaceutical; Advisory / Consultancy, Research grant / Funding (institution): Chugai Pharmaceutical; Research grant / Funding (institution): Kyowa Hakko Kirin; Research grant / Funding (institution): Ono Pharmaceutical; Research grant / Funding (institution): AstraZeneca; Research grant / Funding (institution): Baxalta Japan Limited; Research grant / Funding (institution): Merck Serono; Research grant / Funding (institution): Nano Carrier; Research grant / Funding (institution): Takara-Bio. M. Ueno: Honoraria (self), Research grant / Funding (institution): Yakult Honsha; Honoraria (self), Research grant / Funding (institution): Taiho Pharmaceutical; Honoraria (self), Research grant / Funding (institution): AstraZeneca; Research grant / Funding (institution): ASLAN; Research grant / Funding (institution): Ono pharmaceutical; Research grant / Funding (institution): Daiichi Sankyo; Research grant / Funding (institution): MSD; Research grant / Funding (institution): Merck Serono; Research grant / Funding (institution): Eli Lilly; Research grant / Funding (institution): Boehringer Ingelheim; Research grant / Funding (institution): Beigene; Research grant / Funding (institution): Bayer; Research grant / Funding (institution): Eisai; Honoraria (self): Novel pharma; Honoraria (self): Novartis; Honoraria (self): Teijin Pharma; Research grant / Funding (institution): Takara Bio.

701P - Outcomes of first-line FOLFIRINOX (FFX) versus gemcitabine and nab-paclitaxel (GN) in patients with advanced pancreatic cancer: Multi-Institutional Canadian sites experience

BackgroundFOLFIRINOX (FFX) and Gemcitabine with nab-Paclitaxel (GN) are both proven to be superior to Gemcitabine in first line treatment for advanced pancreatic cancer (APC). However, there has been no phase 3 randomized controlled trials to prove FFX is superior to GN in APC. This population-based cohort study was conducted to compare efficacy and safety profiles of the two standard regimens in APC. MethodsIn this retrospective cohort study, we evaluated all newly diagnosed patients (pts) with APC who received either FFX or GN as first line therapy during 2010-2018 at three Canadian institutions. The primary objective was to assess survival. Secondary objective was to compare safety profile of the two regimens. Kaplan Meier method and log-rank test were used for survival curves. ResultsThere were 231 eligible pts identified: 143 received FFX and 88 received GN. FFX pts were slightly younger than GN (median age: 62 (IQR: 56-67) vs 66 (IQR: 58-73) respectively). There were predominantly more males: FFX 89 (62.2%) vs GN 46 (52.3%). WHO performance status (PS) of 0 were 38 (28.4%) vs 14 (16.5%) and 1 were 90 (67.2%) vs 65 (76.5%) respectively. The median progression-free survival (PFS) of FFX was 5.5 months (mts) (95% CI: 5.0-6.7) vs 5.1 mts (95% CI: 3.8-7.1) with GN (p=0.37). The median overall survival (OS) with FFX was 9.3 mts (95% CI: 7.5 – 11.1) vs. 10.2 mts (95% CI: 6.8-11.3) with GN (p=0.81). On multivariate analysis chemotherapy regimen was not correlated with PFS or OS. There were more grade 3-4 toxicity in FFX vs GN group: diarrhea – 22 (15.4%) vs 3 (3.4%) (p=0.004), nausea – 20 (14%) vs 6 (6.8%), vomiting – 13 (9.1%) vs 6 (6.8%), peripheral sensory neuropathy (PSN) – 8 (5.6%) vs 3 (3.4%), thrombocytopenia – 28 (19.6%) vs 5 (5.7%) (p=0.003) respectively. Gr 3-4 neutropenia rates were similar in both regimens: 23 (16%) in FFX vs 15 (17%) in GN. ConclusionsOur results revealed that FFX or GN had comparable survival and safety profiles. Given lower Gr 3-4 toxicity profile of GN regimen, GN is likely preferable choice for majority of pts. FFX could be reserved for young high performance pts. Legal entity responsible for the studySegal Cancer Centre Jewish General Hospital. FundingHas not received any funding. DisclosureAll authors have declared no conflicts of interest.

Efficacy and safety of Kanglaite injection combined with radiochemotherapy in the treatment of advanced pancreatic cancer

Kanglaite (KLT) injection, a kind of Chinese medicine, is considered a promising complementary therapeutic option for malignant cancer treatment. This study aimed to systematically investigate the efficacy and safety of the combination of KLT injection and radiochemotherapy for the treatment of advanced pancreatic cancer (PC). Studies were identified by searching Cochrane Library, Web of Science, PubMed, Embase, China National Knowledge Infrastructure (CNKI), Chinese Biological Medicine Database (CBM), Wanfang database and Chinese Scientific Journal Database (VIP) before October 2018. The primary reported outcomes including efficacy, quality of life (QoL), and adverse events were systematically evaluated. Data from 16 trials with 960 patients with advanced PC were included. Compared with radiochemotherapy alone, the combination of KLT injection and radiochemotherapy significantly improved the 1-year overall survival (OS, odds ratio [OR] = 2.58 95% CI: 1.12-5.93 P = .03), overall response (ORR, OR = 2.16 95% CI: 1.58-2.94 P <.00001) and disease control rates (DCR, OR = 2.50 95% CI: 1.84-3.38 P <.00001). The QoL of patients, who received a combination of radiochemotherapy and KLT injection, also improved compared with radiochemotherapy treatment alone as indicated by the increased quality of life improved rate (QIR, OR = 3.68 95%CI: 2.36-5.75 P <.00001), pain relief rate (PRR, OR = 3.70 95% CI: 2.23-6.14 P <.00001) and weight gain rate (WGR, OR = 3.69 95% CI: 2.22-6.13 P <.00001). Adverse events related to radiochemotherapy including gastrointestinal side effects, nephrotoxicity, leukopenia, thrombocytopenia, and myelosuppression were alleviated (P <.05) when KLT was injected to patients with PC. Evidence from the Meta-analysis suggested that the combinational treatment of radiochemotherapy and KLT injection is more effective in advanced PC treatment than radiochemotherapy alone. Additionally, the combination therapy improved QoL of the patients. KLT injection can alleviate the adverse effects associated with the radiochemotherapy.

Establishment and characterization of the gemcitabine-resistant human pancreatic cancer cell line SW1990/gemcitabine.

Due to its rapid progression, metastasis and resistance to chemotherapy, pancreatic cancer is one of the most malignant tumor types to affect the digestive system. Gemcitabine chemotherapy is typically the first choice of treatment for advanced pancreatic cancer; however, chemoresistance is a major obstacle to successful treatment. In order to elucidate the underlying mechanisms of gemcitabine resistance in pancreatic cancer, the drug-resistant cell line SW1990-gemcitabine (SW1990-GZ) was established using the human pancreatic cancer cell line SW1990. The IC50, resistance index and growth of SW1990 and SW1990-GZ cells were also assessed using 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide (MTT) assays. The cellular uptake of gemcitabine in SW1990 and SW1990-GZ was measured using high performance liquid chromatography (HPLC). The protein expression of p53 was also assessed by western blot analysis. The results demonstrated that the IC50 of SW1990 and SW1990-Gz was 0.07±0.0021 and 87.5±3.24 µg/ml, respectively, and that the resistance index ratio of SW1990-Gz was 1,250. The growth rate of SW1990-GZ cells was low compared with that of SW1990 cells. The HPLC results indicated that gemcitabine uptake was markedly reduced in SW1990-GZ cells compared with in SW1990 cells at different time points. The protein expression of p53 was significantly higher in GEM-resistant SW1990-GZ cells compared with that in SW1990 cells (P<0.01). These results suggest that a human gemcitabine-resistant pancreatic cancer cell line was successfully established, with stable and significant drug resistance. The results of the present study suggest that the decreased cellular uptake of gemcitabine may serve an important role in gemcitabine chemoresistance in SW1990-GZ cells; thus, this cell line may be used as an effective in vitro model to improve our understanding of gemcitabine-resistance in pancreatic cancer.

Abstract 2188: Comparing effects of small molecular weight compounds on proliferation and chemotaxis of pancreatic cancer cells

Abstract Background &amp; Aims: The new therapy for pancreatic cancer which has the poorest prognosis among malignant tumors is high demand nowadays. The overall 5-year survival rate in all stages of this type of cancer is less than 5%, even with the multimodality therapy, including surgery, chemotherapy and radiotherapy. Although gemcitabine (GEM) is a key drug in the treatment of advanced pancreatic cancer, the therapeutic effect is limited because of drug resistance. Heat shock protein 90 (HSP90) is known to be overexpressed in several types of cancer cells, and its inhibition has shown promise in the treatment of solid malignancies. Src kinases work as a signal switch for multiple molecular signal transduction pathways. The objective of this study is to evaluate an antitumor effect of three kinds of small molecular weight compounds (antimetabolite Gemcitabine, HSP90 inhibitor NVP-AUY922, and Src kinase inhibitor Dasatinib) on tumor growth and chemotaxis in pancreatic cancer cell lines. Methods: Pancreatic cancer cell lines were treated with each of the 3 compounds to examine the effect on proliferation assay, apoptosis assay, Western blotting, and chemotaxis assay. Results: Of these compounds, HSP90 inhibitor inhibited cell proliferation in pancreatic cancer cells best in a dose- and time-dependent manner. Growth inhibitory effect of HSP90 inhibitor for pancreatic cancer cells were highest of the three. Further, HSP90 inhibitor inhibited the growth of gemcitabine sensitive and resistant pancreatic cancer cell lines. With flowcytometry and immunostaining, HSP90 inhibitor had higher apoptosis-inducing effect than gemcitabine. In the chemotaxis assay, HSP90 inhibitor inhibited the migration of pancreatic cancer cell best in the three compounds. In western blotting, HSP90 inhibitor suppressed the expression of multiple receptor tyrosine kinase proteins as well as the signal transduction in PI3K-Akt and RAS-MAPK pathways. Conclusion: In this study, HSP90 inhibitor was the best of 3 small molecular compounds and has proven effective in gemcitabine sensitive and resistant pancreatic cancer. The HSP90 inhibitor is useful as an antitumor drug by inhibiting proliferation and chemotaxis of pancreatic cancer cells through multiple kinase pathways. Citation Format: Masahiro Yamamura, Akira Yamauchi, Naoki Katase, Masakiyo Sakaguchi, Yosuke Katata, Hiroaki Tanioka, Makoto Okawaki, Takeshi Nagasaka, Yoshiyuki Yamaguchi. Comparing effects of small molecular weight compounds on proliferation and chemotaxis of pancreatic cancer cells [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 2188.

Alpha Radiation Emitters Device for the Treatment of Advanced Pancreatic Cancer

Alpha Radiation Emitters Device for the Treatment of Advanced Pancreatic Cancer

Oral chemotherapy as second-line treatment option for gemcitabine-refractory advanced pancreatic cancer with poor performance status.

405 Background: There is few data for effective second-line treatment in advanced pancreatic cancer, and most patients have poor performance status after progressive disease. We evaluated the efficacy, toxicity, and median dose intensity of oral chemotherapy, capecitabine, or TS-1 in gemcitabine-refractory advanced pancreatic cancer for second-line treatment. Methods: Patients who have progressive disease after first-line gemcitabine-based chemotherapy were retrospectively analyzed between Jan. 2011 and Nov. 2017. These patients were treated with capecitabine or TS-1 as second-line treatment. Capecitabine were administered as 2,500 mg/m2 divided dose on day 1-14, followed by one week rest. In TS-1 group, TS-1 was taken orally based on patient’s BSA (60mg twice daily in BSA &gt; 1.5, 50mg twice daily in BSA 1.25-1.5, and 40mg twice daily in BSA &lt; 1.25) through 28 days, by two week rest. Median dose intensity was compared by calculating a percent of target dose achieved in the average cycle for each patient. Results: Of the total 62 patients, 41 patients were treated with capecitabine and 21 patients were treated with TS-1. The median age was 61 years for the capecitabine group compared with 62 years for the TS-1 group. In capecitabine group, males were 56%, and in TS-1 group, males were 66%. 29% of capecitabine group received prior fluorouracil base therapy, and 47% of TS-1 group were receiving such therapy. The objective response rate was similar in the two groups: 12.2% with capecitabine and 4.8% with TS-1 (p = 0.358). There was no difference in median progression free survival between capecitabine and TS-1 (2.1 months vs. 2.7 months, p = 0.102), however, TS-1 group showed better median overall survival time than capecitabine group (6.9 months vs. 4.6 months, p = 0.048). Most of the adverse events were similar in both group, except that grade 3 or 4 mucositis was more common in TS-1 group. There was no significant difference in median dose intensity between two groups. (Capecitabine 91.5% vs. TS-1 90.1%, p = 0.216). Conclusions: Oral agents such as TS-1 or capecitabine can be second-line treatment for advanced pancreatic cancer patients with poor performance status after progression to gemcitabine-based regimen.

Clinical status of high-intensity focused ultrasound in the treatment of advanced pancreatic cancer

Pancreatic cancer is a common malignancy of the digestive system, which is difficult for early diagnosis and surgical resection. Currently, the main clinical treatment strategies are not effective. High-intensity focused ultrasound (HIFU), for its non-invasive characteristic, with combination therapy, such as chemotherapy, radiotherapy and traditional Chinese medicine, has made great progress in the clinical treatment of advanced pancreatic cancer. This literature will review the clinical status of HIFU in in the treatment of advanced pancreatic cancer, in order to provide references for the study of pancreatic cancer. Key words: Pancreatic neoplasms; High-intensity focused ultrasound ablation; Combined modality therapy; Clinical medicine

Nab-paclitaxel plus gemcitabine as first-line treatment for advanced pancreatic cancer: a systematic review and meta-analysis.

To evaluate the effectiveness of nab-paclitaxel plus gemcitabine (NG) as a first-line treatment for advanced pancreatic cancer. A meta-analysis was performed to assess the impact on the objective response rate (ORR), survival rate and grade 3/4 adverse events. Of the 2,056 patients included from 26 studies, the median overall survival ranged from 6.9 months to 24.7 months, with a 1-year survival rate of 45.2% (95%CI: 35.8% -54.5%). The 6-month progression-free survival rate was 41.0% (95%CI: 30.5% - 51.4%), and the ORR was 31.6% (95%CI: 26.7% - 36.6%). Fifty locally advanced pancreatic cancer (LAPC) patients underwent surgery and had an R0 resection rate of 52.0%. No death was caused by toxicity, and 1,329 grade 3/4 adverse events were reported in 1,353 patients. NG has been proven to reduce tumours with an acceptable toxicity profile in metastatic pancreatic cancer. This analysis further demonstrates the efficacy and safety of NG for treating LAPC.

High-intensity focused ultrasound ablation for advanced pancreatic cancer.

The aim of this study was to evaluate the efficacy, safety, and survival factors of high-intensity focused ultrasound (HIFU) ablation in the treatment of advanced pancreatic cancer. A retrospective analysis was conducted between September 2010 and March 2016. Advanced pancreatic cancer patients with HIFU treatment were enrolled in the analysis to evaluate the efficacy of local ablation, pain relief, and relative complications of HIFU therapy. The main factors that affected Overall survival rate (OSR) and median survival time (MST) were also analyzed. Eighty-six patients received HIFU treatment, with a total of 93 treatments performed, and 83 cases were evaluated. Complete response rate (RR) was 3.6% (3/83) and partial RR was 79.5% (66/83). After HIFU treatment, pain reduction was observed in 74 patients, and the total remission rate was 97.6% (74/76). The total MST was 9.9 months (2-58.7 months), the total OSR in 1 and 2 years was 41.5% and 9.6%, respectively. Minor complications occurred in 97.7% (42/43) patients, including transient fever, abdominal pain, skin burn, and amylase elevation. The univariate analysis showed that the clinical stage, treatment method, ablation efficacy, and combined treatment were significant prognostic factors. HIFU can significantly alleviate cancer-related pain and prolong the survival time of patients with pancreatic cancer.

Modulated Electro-Hyperthermia as Palliative Treatment for Pancreatic Cancer: A Retrospective Observational Study on 106 Patients

Background: Pancreatic adenocarcinoma has a poor prognosis, resulting in a <10% survival rate at 5 years. Modulated electro-hyperthermia (mEHT) has been increasingly used for pancreatic cancer palliative care and therapy. Objective: To monitor the efficacy and safety of mEHT for the treatment of advanced pancreatic cancer. Methods: We collected data retrospectively on 106 patients affected by stage III-IV pancreatic adenocarcinoma. They were divided into 2 groups: patients who did not receive mEHT (no-mEHT) and patients who were treated with mEHT. We performed mEHT applying a power of 60 to 150 W for 40 to 90 minutes. The mEHT treatment was associated with chemotherapy and/or radiotherapy for 33 (84.6%) patients, whereas 6 (15.4%) patients received mEHT alone. The patients of the no-mEHT group received chemotherapy and/or radiotherapy in 55.2% of cases. Results: Median age of the sample was 65.3 years (range = 31-80 years). After 3 months of therapy, the mEHT group had partial response in 22/34 patients (64.7%), stable disease in 10/34 patients (29.4%), and progressive disease in 2/34 patients (8.3%). The no-mEHT group had partial response in 3/36 patients (8.3%), stable disease in 10/36 patients (27.8%), and progressive disease in 23/36 patients (34.3%). The median overall survival of the mEHT group was 18.0 months (range = 1.5-68.0 months) and 10.9 months (range = 0.4-55.4 months) for the non-mEHT group. Conclusions: mEHT may improve tumor response and survival of pancreatic cancer patients.

Meta‑analysis of current chemotherapy regimens in advanced pancreatic cancer to prolong survival and reduce treatment‑associated toxicities.

Unresectable advanced pancreatic cancer (APC) is a highly lethal malignancy. Although numerous chemotherapeutic regimens are available, evidence regarding the survival extension, the life quality improvement, the associated risks and occurrence rates of adverse effects, is required. The effects of 19 chemotherapy regimens on survival and treatment-associated toxicities in the context of APC treatment were comparatively assessed. A total of 23 randomized controlled trials were included in this network meta-analysis. For overall survival, five regimens, Gemcitabine (Gem)+radiotherapy (Radio), Gem+cisplatin (Cis), Gem+erlotinib (Erl)+bevacizumab (Bev), Gem+capecitabine (Cap)+Erl, and Gem+exatecan, were the most effective treatments, according to their respective high surface under the cumulative ranking (SUCRA) probabilities. Regarding the progression-free survival, five regimens, including Gem+Radio, Gem+Erl+Bev, Gem+Cis, Gem+Cap+Erl and Gem+pemetrexed, were the most effective treatments based on their SUCRA probabilities. Each regimen exhibited advantages and disadvantages, and 14 common treatment-associated toxicities were present in different proportions. The three principal toxic effects included haematological, gastrointestinal and constitutional symptoms. To improve survival, chemotherapy regimens with high SUCRA probabilities require prioritizing. Although treatment-associated toxicities are unavoidable, the regimens presented toxicities in distinct proportions. Therefore, clinicians should assess the disease status of the patients, and balance the benefits and risks of the selected treatment.

738P - Antibiotics may enhance the efficacy of gemcitabine treatment for advanced pancreatic cancer

738P - Antibiotics may enhance the efficacy of gemcitabine treatment for advanced pancreatic cancer