tbuckley/cabot-search huggingface dataset:
Risk factors for severe neutropenia among pancreatic cancer patients receiving nab-paclitaxel and gemcitabine combination therapy.
Authors: Kazuyoshi Kawakami, Genta Ito, Takeshi Aoyama, Takashi Yokokawa, Masashi Nakamura, Masato Ozaka, Naoki Sasahira, Hayato Kizaki, Masayuki Hashiguchi, Toshihiro Hama, Satoko Hori
Journal: Journal of Clinical Oncology (2020)

684 Background: Albumin-bound paclitaxel (nab-paclitaxel) and gemcitabine combination therapy (GnP therapy) significantly extends overall survival in patients with metastatic pancreatic cancer, compared to conventional gemcitabine monotherapy. However, severe neutropenia (Grade ≥ 3) occurred in 67.6% of patients in the Japanese phase I/II trials of GnP therapy, and is often a limiting factor. The purpose of this study was to identify the risk factors for severe neutropenia in pancreatic patients receiving GnP therapy in clinical settings. Methods: A retrospective study of 222 consecutive patients with pancreatic cancer who received GnP therapy at the Cancer Institute Hospital from December 2014 to December 2016 was conducted. Univariate and multivariate analyses were used to compare blood test values and patients’ characteristics between patients with no neutropenia or Grade 1/2 (non-serious) neutropenia and those with Grade ≥ 3 (severe) neutropenia. Results: There were 19 patients (8.6%) with modified FOLFIRINOX in the previous treatment history. The median doses of nab-paclitaxel and gemcitabine were 192.5 mg (range 134-277.5) and 1,545 mg (range 1,000-2,220), respectively. Severe neutropenia and febrile neutropenia occurred in 118 patients (53.2%) and 15 patients (6.8%), respectively. Multivariate logistic regression analysis indicated that ANC (absolute neutrophil count) &lt; 3.03 x 10 3 /μL (OR: 4.806, 95% CI: 2.416-9.558, p = 0.000), T-Bil ≥ 0.6 mg/dl (OR: 1.964, 95% CI: 1.040-3.708, p = 0.037) and CRP &lt; 0.13 mg/dl (OR: 2.607, 95% CI: 1.331-5.106, p = 0.005) were significant risk factors for severe neutropenia. The incidence rate of severe neutropenia was 85.7% (18/21) in patients with all three identified factors, while it was 27.7% (13/47) in patients with none of them. Age was not a risk factor in either univariate or multivariate analysis. Conclusions: Low ANC, high T-Bil, and low CRP were found to be risk factors for severe neutropenia in patients receiving GnP therapy. It would be desirable to monitor patients with these risk factors carefully, even if their values are within the standard ranges.
Cryotherapy in addition to chemotherapy for palliation of inoperable esophageal cancer: A multicenter prospective study.
Authors: Toufic Kachaamy, Neil R. Sharma, Rahul Pannala, Jeffrey Weber, Kimberly Gorsuch, Yashika Young, Christina Salas, Christina M. Zelt, Heather Werling, Digant Gupta, Pankaj G. Vashi
Journal: Journal of Clinical Oncology (2020)

342 Background: Palliation of dysphagia (Dys) in patients with inoperable esophageal cancer (EC) can be challenging. The major goal of palliation therapy is to improve patient’s quality of life (QoL) and Dys and allow adequate caloric intake. The most commonly used palliative modalities for Dys are radiation therapy (RT) and esophageal stenting. However, RT is limited by total dose and adverse events (AE) in patients receiving systemic therapy (ST), and stenting suffers from a high rate of AE including reflux and chest pain. A relatively new modality of liquid nitrogen endoscopic spray cryotherapy (cryo) has been reported in retrospective studies to improve Dys in patients receiving systemic therapy. We prospectively evaluated Dys and QoL of patients with inoperable EC undergoing cryo in addition to ST for palliation. Methods: A prospective multicenter study of 24 adult inoperable EC patients undergoing cryo and ST for palliation at 4 specialized cancer centers from Sep 2017 to Aug 2019. QoL was assessed using a modified EORTC QLQ-OES18 questionnaire (score 18 to 72, with higher scores indicating worse QoL). Dys was measured using a 4-point Likert scale: 0, no Dys; 1, Dys to solids; 2, Dys to semi-solids; 3, Dys to liquids; 4, Dys to saliva. Paired t-test was used to evaluate change in QoL and Dys between pre- and post-cryo. Results: There were 19 males and 5 females (17 stage IV, 5 stage III, and 2 stage II at diagnosis). Among 24 patients, a total of 71 cryo were performed, with a mean of 2.9 treatments per patient. After a median follow-up of 2 months, the mean EORTC score improved significantly from 35.4 at baseline to 25.5 at last follow-up ( p &lt; 0.001). Similarly, the Dys score improved significantly from 2.0 at baseline to 0.87 at last follow-up ( p &lt; 0.001). Grade 3 or higher AE were seen in only one patient (4%) who had GI bleeding 2 weeks after cryo and was diagnosed with bleeding from severe reflux esophagitis related to gastric outlet obstruction. Conclusions: The analysis of this multicenter prospective study shows that cryo in addition to ST for palliation of EC is well tolerated with significant improvement in Dys and QoL.
Phase II clinical trial of novel agent PBI-05204 in patients with metastatic pancreatic adenocarcinoma (mPDA).
Authors: Marc Thomas Roth, Dana Backlund Cardin, Erkut Hasan Borazanci, Margaux Steinbach, Vincent J. Picozzi, Alexander Rosemurgy, Raymond Couric Wadlow, Robert A. Newman, Jordan Berlin
Journal: Journal of Clinical Oncology (2020)

698 Background: Survival statistics for mPDA are dismal and with limited treatment options novel agents are needed to improve disease outcomes. PBI-05204 (Phoenix Biotechnology, Inc., San Antonio, TX) is a modified supercritical carbon dioxide extract of Nerium oleander leaves. Oleandrin, the extract’s major cytotoxic component, has demonstrated anti-tumor activity in various tumor cell lines. In a human PDA orthotopic model, this preparation reduced tumor burden as monotherapy. Pharmacodynamic studies suggest that PBI-05204’s mechanism of action is through inhibition of the PI3k/Akt/mTOR pathway. Methods: A phase II single-arm, open-label study to determine the efficacy of PBI-05204 in patients (pts) with mPDA refractory to standard therapy was conducted. The primary endpoint was overall survival (OS) with the hypothesis that 50% of pts would be alive at 4.5 months. Secondary objectives included safety, progression-free survival (PFS), and overall response rate. Pts received oral PBI-05204 daily until progressive disease (PD), unacceptable toxicity, or pt withdrawal. Radiographic response was assessed every two cycles. Results: Forty-one pts were enrolled; two never received treatment and one was found to have a neuroendocrine tumor after pathological re-evaluation, leaving 38 pts for analysis. Median age at time of enrollment was 65.0 years. The median time from initial diagnosis to treatment was 16.9 months. The primary reason for withdrawal was PD (45.2%). Ten pts were alive at 4.5 months (26.3%) with a mPFS of 56 days (corresponding to first restaging). One objective response (2.6%) was observed for 162 days. Grade ≥3 treatment-emergent adverse events occurred in 63.2% of pts with the most common attributed to drug (all grades) being fatigue (36.8%), vomiting (23.7%), nausea (18.4%), decreased appetite (18.4%), and diarrhea (15.8%). Conclusions: PBI-05204 did not meet its primary endpoint for OS in this study. Recent preclinical data indicate an efficacious role for PBI-05204 against glioblastoma multiforme when combined with chemotherapy, such as temozolomide, and radiotherapy. A randomized Phase II trial is currently being designed. Clinical trial information: NCT02329717.
Lenalidomide added to standard intensive treatment for older patients with AML and high-risk MDS
Authors: G. J. Ossenkoppele, D. A. Breems, G. Stuessi, Y. van Norden, M. Bargetzi, B. J. Biemond, P. A von dem Borne, Y. Chalandon, J. Cloos, D. Deeren, M. Fehr, B. Gjertsen, C. Graux, G. Huls, J. J. J. W. Janssen, A. Jaspers, M. Jongen-Lavrencic, E. de Jongh, S. K. Klein, M. van der Klift, M. van Marwijk Kooy, J. Maertens, L. Michaux, M. W. M. van der Poel, A. van Rhenen, L. Tick, P. Valk, M. C. Vekemans, W. J. F. M. van der Velden, O. de Weerdt, T. Pabst, M. Manz, B. Löwenberg, D. A. Breems, None Havelange, M-C Vekemans, I. Moors, F. van Obberg, J. A. Maertens, B. Hodossy, S. Vansteenweghen, L. Lammertijn, D. Deeren, C. Graux, A. Sonet, A. Triffet, B. T. Gjertsen, M. Bargetzi, J. Passweg, D. Heim, San Giovanni, Georg Stuessi, T. Pabst, D. Betticher, Y. Chalandon, O. Spertini, M. Gregor, U. Hess, M. Fehr, M. G. Manz, S. K. Klein, B. J. Biemond, G J Ossenkoppele, A. van de Loosdrecht, J J W M Janssen, J. W. J. van Esser, M. Van der Klift, R. E. Brouwer, D. Van Lammeren-Venema, M. D. Levin, L. W. Tick, M. C. J. C. Legdeur, G. Huls, E. Vellenga, M. Hoogendoorn, J. H. Veelken, P. A. von dem Borne, H. C. Schouten, O. de Weerdt, W. J. F. M. van der Velden, J. Cornelissen, M. Jongen-Lavrencic, B. Wouters, H. G. M. Raaijmakers, B. Löwenberg, J. Kuball, A. Van Rhenen, M. Van Marwijk Kooy
Journal: Leukemia (2020)
Phase Ib study to test the safety and activity of pembrolizumab (anti-PD-1) and trebananib (angiopoietin-2 inhibitor [Ang-2]) in patients with advanced solid tumors: Updated analysis of the colorectal cancer (CRC) cohort.
Authors: Osama E. Rahma, James M. Cleary, Kimmie Ng, Benjamin L. Schlechter, Jessica Eno, Anna Maloney, Anita Giobbie-Hurder, David F. McDermott, F. Stephen Hodi
Journal: Journal of Clinical Oncology (2020)

155 Background: Ang-2 is produced by endothelial cells, predominantly in tissues undergoing vascular remodeling. Current studies suggest that Ang-2 partially suppresses T cell activation by increasing PD-L1 expression and decreasing activation of monocytes. We demonstrated that high pre-treatment serum Ang-2 is associated with reduced overall survival in patients treated with PD-1 blockade. We therefore hypothesized that the combination of Ang-2 and PD-1 blockade may be effective for treatment of patients with advanced cancer. Methods: We initiated a phase 1b trial of the combination of pembrolizumab and trebananib, an Ang-1/2 neutralizing peptibody in advanced solid tumors. Treatment consisted of an induction phase of pembrolizumab 200 mg every 3 weeks and trebananib weekly (with an initial run-in dose escalation of 15-30 mg/kg) for 12 weeks followed by pembrolizumab alone for 2 years. Here we present the updated data in the fully enrolled CRC expansion cohort. Results: The study enrolled 18 microsatellite stable (MSS) CRC patients. There were no DLTs in the dose escalation phase, and 30mg/kg was deemed to be the MTD. This summary is based on 15 CRC patients treated with 30 mg/kg trebananib plus pembrolizumab. The most common treatment-related adverse events (AEs) were abdominal distension, diarrhea, limb edema, transaminitis, and proteinuria, each reported in 40% of the patients. As of September 2019 (median follow up of 10 months), 13 patients were off treatment and two were continuing. Eleven patients were off treatment due to disease progression and 2 due to unacceptable toxicities (grade 4 pneumonitis and grade 3 transaminitis). The response rate was 7% (1 partial response for 23.8+ months) and the disease control rate was 27%, with 4 stable disease for a median of 10 months (4-18 months). Median time to progression and overall survival were 2.8 months (90% CI: 1.5 to 8.1 months) and 9.0 months (90% CI: 2.6 months to ∞), respectively. Conclusions: The combination of pembrolizumab and trebananib is well tolerated and demonstrated promising activity in patients with heavily treated MSS CRC. Clinical trial information: NCT03239145.
Outcomes of Older Patients with <i>NPM1</i> Mutated and <i>FLT3</i>‐ITD Negative Acute Myeloid Leukemia Receiving Allogeneic Transplantation
Authors: Madlen Jentzsch, Juliane Grimm, Marius Bill, Karoline Goldmann, Julia Schulz, Dietger Niederwieser, Uwe Platzbecker, Sebastian Schwind
Journal: HemaSphere (2020)

Supplemental Digital Content is available in the text
Gefitinb along with methotrexate as palliative therapy in PS 3 and above in metastatic esophagus squamous cell carcinoma with focus on Q-TWIST.
Authors: VIDYA SAGAR DUSI, Obul Reddy C, Suresh VS Attili, Satya Dattatreya Palanki
Journal: Journal of Clinical Oncology (2020)

355 Background: Metronomic therapy is proven method for treatment of terminally ill patients with malignancy, who are not fit for chemotherapy. The median PFS was significantly superior in responders in previous Indian experiences. However most of them were done in head and neck cancers.The prognosis of patients with metastatic esophageal cancer remains poor with only option being symptomatic care. As the previous experiences show metronomic therapy is safe among various options and there is no study focusing on Quality-Adjusted Time Without Symptoms or Toxicity (Q-TWiST) in southern Indian population,we thought of evaluating the same. Methods: Details of 42 subjects with refractory or progressive metastatic squamous cell carcinoma esophagus having PS &gt; 2 were evaluated. Case records between 2017 September and 2018 September were analyzed for TWIST and QOL. Patients received Gefitinib (250 mg/day), Methotrexate 15 mg IM weekly or in combination. Patients were stratified into those with improved PS and those without. The subjects without PS improvement were continued on the single agent and those with improvement were offered additional chemotherapy based on physician/ patient preference. Metronomic therapy could be continued beyond disease progression- if there is TWIST/QOL improvement. Results: Out of 42 subjects, 29 had improvement in the PS and were continued later. 9 had stable PS and disease. 4 had worsening of PS. 34 subjects have clinically meaningful response (stable disease + complete + partial responses) and had symptomatic improvement. The median number of cycles was 6 (4–11). The median PFS was 198 days (95% CI, 174 to 214), and the median improvement in QOL was 6 points on a scale of 25. Grade II/IV toxicities were observed in 21 (50%) cases predominantly skin rash, stomatitis and diarrhea. Conclusions: Metronomic therapy is well tolerated and may have a role in the treatment of advanced cancers with poor performance status. 67% of the patients who are otherwise not eligible for any active therapy became eligible and had better QOL and longer PFS, which re-emphasizes role of metronomic therapy in advanced squamous cell carcinoma of esophagus.
Survival benefit of conversion therapy after intensive chemotherapy for unresectable metastatic gastric cancer: A propensity score-matched analysis.
Authors: Hiroyuki Ohnuma, Yasushi Sato, Ginji Omori, Naoki Onoyama, Saki Ameda, Ryo Ito, Kota Hamaguchi, Naotaka Hayasaka, Masanori Sato, Kazuyuki Murase, Kohichi Takada, Koji Miyanishi, Tatsuya Ito, Takayuki Nobuoka, Ichiro Takemasa, Junji Kato
Journal: Journal of Clinical Oncology (2020)

354 Background: The significance of conversion therapy (CT), whereby patients (pts) with unresectable disease respond to chemotherapy and subsequently receive surgery with curative intent (adjuvant surgery: AS), has been specifically established for metastatic colorectal cancer. However, such a strategy for advanced or recurrent gastric cancer (AGC) remains controversial. This study aims to clarify the clinical significance of CT for AGC. Methods: In this retrospective multi-institution observational study, we analyzed 168 AGC pts who received chemotherapy consisting of docetaxel, cisplatin or oxaliplatin, and S-1 ± trastuzumab between 2003 and 2019. We divided pts into two groups: those who underwent CT (group CT) or chemotherapy only (group C). Propensity score analysis with 1:1 matching minimized confounding bias when comparing efficacy and safety between groups. Results: A tumor response to chemotherapy was observed in 82.4% of all cases, while 34.5% (58/168) underwent AS. Fifty-one of the 58 pts underwent an R0 resection, and 79.3% were deemed histological responders. After matching, 44 pairs of C and CT pts were selected; significant differences in baseline characteristics were not observed. Incidences of adverse events during chemotherapy were similar between groups, with neutropenia and febrile neutropenia as common grade 3–4 events. Compared with group C, group CT had a significantly better median overall survival (OS) (15.5 vs. 46.0 months; hazard ratio [HR] 0.32; 95% confidence interval [CI] 0.18–0.58; p &lt; .001), and a prolonged progression-free survival (6.5 vs.22.6 months; HR 0.33; 95% CI 0.19–0.56; p &lt; .001). Subgroup analysis of OS showed a favorable trend for CT for almost all parameters. In a multivariate analysis, ECOG performance status (HR 0.10; 95% CI 0.03–0.31) and AS (HR 0.20; 95% CI 0.10–0.40) correlated with favorable OS. In the CT group, pathological response was an independent prognostic factor (HR 0.16; 95% CI 0.06–0.39). Conclusions: CT was associated with better outcomes in AGC pts, even after baseline adjustment. Our data warrants further large-scale studies to establish a conversion therapeutic strategy.
Comment on Nauck et al. Effects of Liraglutide Compared With Placebo on Events of Acute Gallbladder or Biliary Disease in Patients With Type 2 Diabetes at High Risk for Cardiovascular Events in the LEADER Randomized Trial. Diabetes Care 2019;42:1912–1920
Authors: Marko Skelin, Dario Rahelić, Petar Skelin, Marko Lucijanic
Journal: Diabetes Care (2020)

We have read with great interest the post hoc analysis of the Liraglutide Effect and Action in Diabetes: Evaluation of Cardiovascular Outcome Results (LEADER) randomized trial that investigated effects of liraglutide on incidence of acute gallbladder or biliary disease (uncomplicated gallbladder stones, complicated gallbladder stones, cholecystitis, and biliary obstruction) (1). In this study, time-to-first-event analysis was performed by Cox regression, and it documented increased risk of acute gallbladder or biliary disease with the use of liraglutide compared with placebo (hazard ratio 1.60; 95% CI 1.23, 2.09; P < 0.001). In addition, trends toward the increased incidence were observed for each of the four categories of gallbladder- or biliary tract–related events. Although results of this study …
The association between COX-2 polymorphisms and hematologic toxicity in patients with advanced non-small-cell lung cancer treated with platinum-based chemotherapy.
Authors: Zhou Fei
Journal: Journal of Clinical Oncology (2013)

e19059 Background: Overexpression of COX-2 is thought to contribute to tumor promotion and carcinogenesis through stimulating cell proliferation, inhibiting apoptosis, and enhancing the invasiveness of cancer cells. Apoptosis-related molecules are potential predictive markers of survival and toxicity outcomes for platinum treatment. This study aimed to investigate the association between COX-2 polymorphisms and the occurrence of grade 3 or 4 toxicity in advanced non–small cell lung cancer patients treated with platinum-based chemotherapy. Methods: Two hundred and twelve patients with inoperable stage IIIB-IV receiving first-line chemotherapy between 2007 and 2009 were recruited in this study. Four functional COX-2 polymorphisms were genotyped by PCR-based restriction fragment length polymorphism (RFLP) methods. Results: The incidence of grade 3 or 4 hematologic toxicity was significantly higher in G allele carriers of the COX-2 −1195G/A (rs689466) polymorphism compared to wild-type homozygotes AA (P value = 0.013; odds ratio, 2.30; 95% confidence internal, 1.20-4.42) and still significant after a Bonferroni correction. More statistically significant difference was found in grade 3 or 4 leukocytopenia (P value = 0.010; OR=2.28; 95%CI=1.28-6.05). No other significant association between genotype and toxicity was observed in the study. The haplotype analysis showed the haplotype AGG was associated with a reduced risk of grade 3 or 4 hematologic toxicity (P value= 0.015; OR= 0.61; 95%CI =0.41-0.91) while the haplotype GGG was associated with an increased risk of grade 3 or 4 hematologic toxicity (P value=0.008; OR=1.71; 95%CI=1.15-2.54), global X 2 = 6.9825, df =2, P = 0.030. Conclusions: This investigation, for the first time, suggests that polymorphism in COX-2 −1195G/A may be a useful bio-marker to predict severe hematologic toxicity in NSCLC patients after platinum-based chemotherapy.
Plasma deoxyuridine levels in metastatic colorectal cancer (mCRC) patients and clinical response after 5FU based therapy in combination with arfolitixorin.
Authors: Helena Anna Taflin, Elisabeth Odin, Göran Ulf Carlsson, Roger Tell, Bengt Gustavsson, Yvonne Wettergren
Journal: Journal of Clinical Oncology (2020)

185 Background: 5-Fluorouracil (5FU) is one of the most commonly used cancer drugs. FdUMP is a metabolite from 5FU which inhibits thymidylate synthase (TS). TS inhibition causes a rise in the intracellular pool of the natural TS substrate dUMP leading to increased global levels of deoxyuridine (dUR). In order to increase TS inhibition, 5FU is combined with folates, usually leucovorin (LV). However, LV needs enzymatic conversion to become active. The LV conversion capacity differs between patients, with the consequence that many patients will have a reduced effect of 5FU-based treatment. Arfolitixorin is a biologically active folate, 5,10-methylenetetrahydrofolate, which doesn´t need enzymatic conversion; hence it could potentially be more efficacious. Methods: ISO-CC-005 is a phase I/II safety and tolerability study in mCRC patients receiving 5FU/arfolitixorin alone or in combination with irinotecan or oxaliplatin ± bevacizumab. Efficacy was evaluated as Overall Response Rate (ORR) after 4 cycles of chemotherapy. A LC-MS/MS method was developed for quantification of plasma dUr and 5FU. Blood samples were collected before and 24 h after 5FU administration at the first (C1) and fourth (C4) treatment cycle (n = 33). The C4/C1 ratio for dUr and 5FU, respectively, were calculated.The clinical response, which is an ordered categorical data, was modelled using nominal logistic regression using the ratio C4/C1 and the absolute values C1 and C4 as explanatory variables. Results: A positive correlation between dUr and 5FU levels was seen (r = 0.89, p = 0.0011) at C4. The C4/C1 ratio for dUr and 5FU in plasma correlated positively (r = 0.95, p = 0.0001). A positive correlation was also found between arfolitixorin dose and plasma levels of dUr (r = 0.44, p = 0.016) at C1, but not at C4. In the model test, the C4/C1 dUr ratio, as well as the individual dUr levels at C1 and C4, had a highly significant effect on ORR (p = 0.0075). Conclusions: The results demonstrate that the arfolitixorin dose has an impact on plasma levels of dUr and also on clinical response. dUr could potentially be an early surrogate marker for TS inhibition in mCRC patients treated with 5FU/arfolitixorin. Clinical trial information: NCT02244632.