bluuebunny/crossref_metadata_2025_split huggingface dataset:
Liver enzymes elevation due to concurrent dexamethasone and lapatinib: Clinical and in vitro evidence.
Authors: Teo Yi Ling , Saetaew Manit , Chanthawong Suthan , Yap Yoon Sim , Chan Eric Chun Yong , Ho Han Kiat , Chan Alexandre 
Published: March 2020

e13023 Background: Concomitant usage of lapatinib (L) and dexamethasone (D), which are cytochrome P450 (CYP) 3A4 substrate and inducer respectively, may increase the formation of potentially hepatotoxic reactive L metabolites. This study aims to evaluate the effect of D on the occurrence of liver enzyme elevation and to ascertain its role using a parallel in vitro experiment. Methods: Clinical effects of D on L-induced liver enzyme elevation were evaluated in a nested case-control study. Liver enzyme elevation is defined as the first clinically significant change (from baseline) of either total bilirubin (TB), alanine aminotransferase (ALT) or aspartate aminotransferase (AST) by at least 1 grade, based on the Common Terminology Criteria for Adverse Events (CTCAE) version 4.02. In the in vitro study, metabolically-competent transforming growth factor α mouse hepatocytes (TAMH) cells were treated with L and viabilities were compared in the presence or absence of D. Results: Among 97 patients, liver enzyme elevation episodes (87.5% vs. 60.3%, p=0.01) and ALT elevation (41.7% vs. 19.2%, p=0.03) occurred more frequently among patients receiving concomitant L+D comparing to L only. After adjusting for confounders (age, liver and brain metastasis, baseline liver function test (TB, AST, ALT, alkaline phosphatase), underlying liver disease, concurrent use of hepatotoxic medications), patients receiving concomitant L+D were 3.48 times (95% CI 1.24-9.80, p=0.02) and 4.57 times (95% CI 1.23-16.88, p=0.02) more likely to develop a change in ALT and among all liver enzymes respectively. Parallel to our clinical findings, treatment of TAMH cells with L reduced viability in a concentration-dependent manner. The introduction of D further reduced the viability. At 5 µM of L, the introduction of 10 µM and 20 µM of D resulted in a 19% and 59% decrease in viability respectively. Conclusions: The concomitant usage of L+D was associated with an increased occurrence of liver enzyme elevation. The in vitro findings have provided commensurating evidence on the role of D that increases the formation of L-derived hepatotoxic metabolites.
Impact of weight and creatinine measurements in carboplatin dosing.
Authors: Boumedien Feriel , Arsenault Youri , LeTarte Nathalie 
Published: March 2020

e13027 Background: Controversy surrounding weight in Carboplatin dosing is still current. Also, new methods of measuring serum creatinine have raised more questions regarding the precision of Carboplatin dose calculations. The two objectives of this study were to evaluate the impact of alternative weight indicators (actual and adjusted body weight) in the Cockcroft–Gault equation and the use of different creatinine measurements (standard and IDMS) in order to accurately predict Carboplatin dose. Methods: We performed a retrospective chart review on all patients who received at least one dose of Carboplatin between March 7th and May 8th 2010. The patients were divided into two groups according to their body mass index (BMI): 20 < BMI < 27 and BMI ≥ 27. The differential creatinine clearance and Carboplatin dose were assessed in each group using the actual body weight and the adjusted body weight with IDMS creatinine. Moreover, for patients who had their creatinine measurement at the CHUM hospital, we calculate the difference in Carboplatin dose by using the standard creatinine (SC) measurement and IDMS creatinine with the same weight. Results: A total of 95 patients, representing 119 Carboplatin doses, were included in the analysis. 82% were women and median age was 63. The average BMI was 26,6. The Carboplatin expected AUC was 5 for 89% of patients and Carboplatin was associated to Paclitaxel in 78% of patients. In patients with a 20<BMI< 27 (44%), the average difference between the calculated dose using their actual body weight and adjusted body weight was +6.03% (95% CI, 5.2 to 6.9%). For patients with a BMI ≥ 27 (43%), the mean dose difference was +20.6% (95% CI, 18.8 to 22.5%). The use of SC or IDMS creatinine led to a discrepancy in doses of 5.2% (95% CI, 4.7 to 5.7%) for patients with BMI <27 (35 patients) and 5.5% (95% CI, 4.9 to 6.2%) for those with BMI ≥ 27 (23 patients). Conclusions: Based on these findings, we decide in our clinic, to use the actual body weight for patients with a BMI between 20 and 27, and the adjusted body weight for those with a BMI ≥ 27. We also chose not to modify our doses based on the type of the serum creatinine measurement.
Safety and efficacy of dendritic cell immunotherapy with ad-GMCAIX in an immunocompetent preclinical tumor model of renal cell carcinoma.
Authors: Birkhäuser Frédéric D. , Koya Richard C. , Neufeld Caleb , Lu Xuyang , Micewicz Ewa D. , Chodon Thinle , Atefi Mohammad , Kroeger Nils , Rampersaud Edward N. , Chandramouli Gadisetti V.R. , Li Gang , Said Jonathan W. , Ribas Antoni , McBride William H. , Kabbinavar Fairooz F. , Pantuck Allan J. , Belldegrun Arie S. , Riss Joseph 
Published: March 2020

e13045 Background: We have previously reported the successful ex vivo generation of hCAIX-specific cytotoxic T lymphocytes (CTLs) by adenoviral (Ad) transduction of the GMCAIX fusion protein in dendritic cells (DC). We then produced GMP-grade material (NIH-RAID program, NSC 740833). Now we test, for the first time, the in vivo anti-tumor activity of DC-Ad-GMCAIX against renal cell carcinoma (RCC) in a unique immunocompetent mouse tumor model. Methods: Tumor growth inhibition and specificity were studied in BALB/c mice s.c. transplanted with either syngeneic RENCA cells transduced with hCAIX (URCAIX) or with non-hCAIX-expressing RENCA cells (RENCA). In a tumor prevention model, cohorts of mice were first immunized s.c. twice with DC-Ad-GMCAIX, DC-Ad-null, or no DCs, followed by tumor challenge with s.c. transplantation of URCAIX or RENCA cells. In an intervention model, tumors were first established and then immunotherapy was employed. Tumor volume and body weight were regularly assessed. Partial necropsy, immunohistochemistry of harvested tumors, and complete blood count were performed at termination of each study. Results: In the prevention model, URCAIX tumor growth was specifically and significantly inhibited for 15 days (p<0.0001). At termination, median growth inhibition reached 79% (113 vs. 531 mm3) and half of the mice remained tumor-free. In the intervention model, DC-Ad-GMCAIX-treated mice showed specific and significant growth inhibition of URCAIX tumors for 8 days (p<0.0018) with a median growth inhibition reaching 60% (487 vs. 1,205 mm3). The threshold of 15% weight loss was delayed in the therapeutic groups of both models (p<0.0167). No treatment-related weight loss or organ toxicity was observed. hCAIX staining was absent or minimally present in URCAIX-tumors that evaded DC-Ad-GMCAIX therapy. Conclusions: DC-Ad-GMCAIX therapy in a novel immunocompetent mouse model demonstrated, for the first time, both tumor prevention and growth inhibition of established RCC tumors without evidence of systemic toxicity. These studies form the basis for first-in-human clinical trial in patients with advanced RCC.
Phase I trial of everolimus, gemcitabine and cisplatin for patients with solid tumors refractory to standard therapy.
Authors: Costello Brian Addis , Qi Yingwei , Borad Mitesh J. , Kim George P. , Northfelt Donald W. , Erlichman Charles , Alberts Steven R. 
Published: March 2020

e13052 Background: The combination of GEM and CDDP has shown activity in a variety of cancers, including biliary tract/gallbladder. Preclinical testing shows a potential benefit to the addition of EV. Methods: Using a standard 3+3 design, the MTDs of GEM + EV (Cohort I) and GEM + CDDP + EV (Cohort II) were determined as shown in the table. The MTD was defined as the dose level below the lowest dose that induces a DLT in at least one-third of pts. At the MTD of Cohort II, 10 patients were enrolled with biliary tract/gallbladder cancer (Cohort III). A weekly CBC was obtained. Assessments occurred every 3 weeks and imaging for response at every other cycle. Results: In Cohort I (N=12), no DLT occurred at dose level 0, and in dose level 1, grade 3 thrombocytopenia was found in 2 of 6 pts. The MTD for Cohort I was determined to be dose level 0. Responses were seen in 3 pts: 2 CRs (primary peritoneal, pancreatic) and 1 PR (breast). In Cohort II (N=15) DLTs at dose level 0 were neutropenia and thrombocytopenia in 2 of 3 pts and at dose level -1, thrombocytopenia in 2 of 6 pts. At dose level -2, 1 of 6 pts experienced a DLT (grade 3 thrombocytopenia), establishing this dose level as the MTD. Responses were seen in 2 pts, both PRs (ampullary, pheochromocytoma). All 10 pts have been enrolled in Cohort III with 2 DLTs (neutropenia and thrombocytopenia). Stable disease seen in 5 of 7 evaluable pts. Conclusions: Gem + EV was well tolerated at dose level 0, though dose escalation was limited by thrombocytopenia. GEM + CDDP + EV had DLTs of neutropenia and thrombocytopenia leading to the MTD of dose level of -2. Cohort III is fully accrued and the 2 DLTs are hematologic. [Table: see text]
International guidelines for antithrombotics in cancer patients.
Authors: Farge Dominique , Debourdeau Philippe , Beckers Marielle , Buller Harry ,   Working Group on International Recommandation for Thrombosis and Cancer
Published: March 2020

e13062 Background: Venous thromboembolism (VTE), defined as deep-vein thrombosis (DVT) or pulmonary embolism (PE), including those related to indwelling central venous catheter (CVCT), is reported in 15 to 20% of patients with cancer. To date, VTE impact on oncology patients remains elusive and the increased incidence of cancers and of CVC for chemotherapy leads to an increased number of VTE. Methods: Heterogeneity in clinical practices worldwide, and lack of international recommendations led us to establish international guidelines for the management of VTE in cancer patients according to the GRADE methodology. These international guidelines were elaborated under the auspices of the International Society of Thrombosis and Haemostasis (ISTH) following an initiative from the “Groupe Francophone Thrombose et Cancer” (GFTC,www.thrombose-cancer.com) with the collaboration of the Academic Medical Centre (AMC), Amsterdam, The Netherlands, and the methodological support and quality control of the French national cancer institute (INCa). A literature review of the studies published on this topic between 1996 and 2011 was performed. A first version of the guidelines was established based on the corresponding levels of evidence derived from analysis of the selected studies. The recommendations were classified as Strong or Weak according to GRADE and Best Clinical Practices based on international expert’ agreement in the absence of literature data. In the absence of data we provided guidance based on experts opinion. The document was then peer-reviewed by a group of 200 international independent experts. Results: The main topics of the guidelines are the treatment and the prophylaxis of VTE with heparins and vitamin K antagonists in medical and surgical cancer patients, including CVC related thrombosis. Recommendations on the use of vena cava filters, thrombolysis and VTE treatment in patients with intracranial malignancies as well as for prophylaxis in the ambulatory setting are also proposed. Conclusions: These first international guidelines, the methodological steps, the data analysis and critical appraisal, the conclusions with their levels of evidence and the argued judgement of the experts will be available on the GTC, INCa and ISTH web sites
Retrospective analysis of intravenous iron-sucrose therapy in patients undergoing chemotherapy at a tertiary-care center in India.
Authors: Bajpai Jyoti , Gupta Sudeep , Shah Kajal , Ghosh Jaya , Noronha Vanita , Prabhash Kumar , Kanujia Arti 
Published: March 2020

e13068 Background: Cancer patients frequently have anemia as a result of nutritional deficiencies, malignancy or its treatment. Administration of intravenous (IV)-iron is a therapeutic option in cancer patients with iron-deficiency-related-anemia. Methods: This is a single-institution retrospective-study of 399 patients who were undergoing chemotherapy for non-myeloid malignancies from January 2006 to December 2009 and had hemoglobin ≤11 gm/dl. They received two doses of iron-sucrose, 200-300 mg each as short IV- infusion, 3 weeks apart. The data was recorded at baseline and 3-6 weeks after IV-iron administration in all patients. Results: Of 399 patients, 326(81.7%) had non-hematological malignancies. Transferrin-saturation (TSA) was available in 149 patients. The mean (range) baseline hemoglobin, mean-corpuscular-volume (MCV) and TSA were 9.75(8.0-11.3) gm/dl, 82.4(52.5-100.3) fl and 18.38 (5.2-34.0)%, respectively. After 2 doses of IV-iron hemoglobin increased in 340 (85.2%), reduced in 32 (8.0%) and did not change in 27 (6.7%) patients. The mean (range) increase in hemoglobin was 0.7 (-3.2 to +3.2) g/dl in all patients and 0.95 (0.1-3.2) g/dl in 340 patients in whom it increased after IV-iron. The data were analyzed by low (≤ 83 fl) versus normal (>83 fl) MCV and low (≤20%) versus normal (>20%) TSA. Hemoglobin increased more than the mean increment (0.7 g/dl) in 63.8% patients with low MCV compared to 39.2% of patients with normal MCV (p=0.002). Hemoglobin increased more than the mean increment (0.7 g/dl) in 60.4% of patients with low TSA compared to 58.6% with normal TSA (p=0.479). These results suggest that IV iron was more efficacious in patients with low MCV. Two patients (0.005%) developed anaphylactic shock during or shortly after IV-iron administration and 35 (11.7%) had minor side effects. Thirty (7.5%) patients received RBC transfusions during their continued chemotherapy. Conclusions: Intravenous-iron improved hemoglobin during continued chemotherapy in the large majority of cancer patients with anemia and was safe and tolerable. Low MCV might serve as a surrogate for iron-deficiency-microcytic-anemia in developing-world.
Autologous cytokine-induced killer and dentritic cells in treatment of advanced and unresectable lung cancer.
Authors: Zhang Lei , Li Baoping 
Published: March 2020

e13069 Background: Both experimental and clinical studies showed cytokine-induced killer (CIK) cells have been shown capable of efficiently lysing target tumor cells, which activity can be enhanced by dendritic cell (DC) stimulation. This study demonstrated that co-cultured autologous CIK and tumor antigen-pulsed DC are effective in in treatment of advanced and unresectable lung cancer Methods: Sixteen patients having stage III-IV lung cancer with a malignant pleural effusion, 9 females and 7 males with an average age of 54.3 years old, were included in this study. Autologous CIK and DC were prepared from isolated peripheral blood mononuclear cells and were induced by multiple cytokines. Generated DCs were pulsed by the antigen generated from tumor tissues and co-cultured with CIK. Those patients received 4-6 times of CIK-DC intravenous infusion, 2-3 ×109 cells each time. Results: Eleven (68.8%) patients achieved a partial remission. The pleural effusion decreased in all those patients, and in 9 of them the effusion decreased over 50%. The clinical symptoms were relieved in all the patients. There were no significant adverse effects were found. Those patients are still followed for long-term survival outcome. Conclusions: CIK-DCs immunotherapy provides a new and effective treatment for the late stage lung cancer.
In vitro chemosensitivity assay for patients with gynecologic sarcoma.
Authors: Santin Alessandro , Varughese Joyce , Chan John K. , McClure Candace , Lea Jayanthi 
Published: March 2020

e13078 Background: This study describes the in vitro drug response of gynecologic sarcomas and clinical implications of in vitro testing. Methods: Ovarian or uterine sarcomas were analyzed for response to any of 7 drugs (carboplatin [Carb], cisplatin [Cis], paclitaxel [Ptx], docetaxel [Dtx], doxorubicin [Dox], gemcitabine [Gem], Ifosfamide [Ifo]) with a chemosensitivity assay (ChemoFx, Precision Therapeutics, Inc, Pittsburgh PA). In combination therapy, tumors were considered sensitive if responsive to at least 1 drug. Results: 68 tumors were analyzed (21 ovarian and 47 uterine; 54 primary and 14 recurrent; carcinosarcoma [n=53], leiomyosarcoma [n=13], other [n=2]). 24% of tumors were responsive to Carb, 30% to Cis, 33% to Ptx, 9% to Dtx, 18% to Dox, 26% to Gem, 27% to Ifo, 40% to Carb+Ptx, 39% to Cis+Ifo, 48% to Ptx+Ifo, 24% to Gem+Dtx, and 27% to Gem+Dox (Table). Ovarian sarcomas were more responsive than uterine sarcomas and primary more than recurrent tumors. Carcinosarcomas were more responsive than leiomyosarcomas to Ifo (P=0.02). Conclusions: In vitro tumor response testing may enable physicians to individualize chemotherapy regimens for their patients. [Table: see text]
Molecular mechanism of in vitro pemetrexed sensitivity according to histological type in non-small cell lung cancer.
Authors: Yoshida Tsukihisa , Yano Tokujiro , Kohno Mikihiro , Haro Akira , Okamoto Tatsuro , Maehara Yoshihiko 
Published: March 2020

e13090 Background: Pemetrexed (Alimta, ALM) is a new multitarget antifolate metabolite anticancer drug. Non-small cell lung cancer (NSCLC) is now treated with selective chemotherapy based on its classification as either non-squamous cell carcinoma or squamous cell carcinoma (SCC). This study was designed to investigate the relationship between in vitro chemosensitivity to ALM and both clinicopathological factors and the expressions of ALM-related enzymes and carrier molecule in NSCLC. Methods: Seventy NSCLC samples (56 adenocarcinoma and 14 SCC) were used. Chemosensitivity was assessed by the succinate dehydrogenase inhibition (SDI) test for three antimetabolic anticancer drugs, including ALM, 5-fluorouracil, gemcitabine. Samples showing more than the median of the succinate dehydrogenase (SD) activity, which reflects the cell viability, were defined as "Resistant" and samples showing less than the median were defined as "Sensitive." The mRNA expression levels of target enzymes of ALM (thymidylate synthase (TS), dihydrofolate reductase and glycinamide ribonucleotide formyltransferase), metabolic enzymes of ALM (γ-glutamyl hydrase (GGH) and folypolyglutamate synthase) and reduce folate carrier (RFC) were measured by reverse transcriptase polymerase chain reaction analysis to examine the influence on chemosensitivity to ALM. Results: Of 3 antimetabolic drugs, only ALM showed significant difference of chemosensitivity according to the histological type. SCC samples were more resistant to ALM than adenocarcinoma samples. In adenocarcinoma, no significant relationship between chemosensitivity to ALM and clinicopathological factors was observed. SCC samples showed higher expression of TS and lower expression of RFC than adenocarcinoma samples. In adenocarcinoma, only GGH was inversely correlated with chemosensitivity to ALM. Conclusions: The present study suggested that, in SCC, the expressions of TS and RFC were associated with the chemosensitivity to ALM. In adenocarcinoma, the expression of GGH was associated with the chemosensitivity to ALM.
Perceptions of clinical trials in gastrointestinal/hepatobiliary cancer patients: A comprehensive survey in a Korean tertiary hospital.
Authors: Park Lee Chun , Lee Jeeyun , Kim Hee Young , Choi Moon Ki , Hong Jung Yong , Park Silvia , Maeng Chi Hoon , Do Ingu , Park Se Hoon , Park Joonoh , Kang WonKi , Lim Hoyeong , Park Young Suk 
Published: March 2020

e13094 Background: In the past few years, the volume of clinical trials has increased rapidly in East Asia, especially in Asian prevalent cancer types such as gastric cancer, hepatobiliary cancer. The actual degree of understanding or perceptions of clinical trials by cancer patients have been rarely studied in East Asian countries. Methods: Between July 1st 2011 and November 30th 2011, we conducted a prospective survey study regarding cancer patient’s awareness and willingness to participate a clinical trial. The questionnaire consisted of 21 questions based on an Index of Clinical Trial Understanding. Patients with gastrointestinal/hepatobiliary cancer who visited the Hemato-Oncology outpatient clinic at Samsung Medical Center and signed informed consent form were enrolled. The survey was conducted by a well-trained research nurse and statistical analysis was analyzed at the biostatistics core at SMC. Results: In this survey study, 1,000 patients were asked to participate and 675 patients consented to participate (67.5%). The awareness of clinical trial was substantially higher in patients with higher level of education (p<.001), married (p=.004), and higher economic status (p=.001). Nevertheless, willingness to participate the clinical trial was not significantly increased by higher level of education (p=.286), married (p=.685) and higher income (p=.310). The most common source for acquisition of clinical trial was attending physicians (52.0%) followed by mass media (36.6%), other patients (6.39%), internet (3.3%) and others (1.5%). The most influential factors for patient’s willingness to participate were physician’s opinion (n=181, 26.8%), limited treatment options (n=178, 26.4%), and expectations towards new anti-cancer drug (n=142, 21.0%). Patients were likely to refuse to participate a clinical trial due to unverified treatment modality (n=320, 47.4%) and negativity for clinical trials (n=193, 28.6%). Conclusions: We surveyed a large patient cohort to specifically inquire willingness and awareness of clinical trial in Asian-prevalent cancer types. Further correlative analyses with various variable will be presented at the meeting.