tbuckley/cabot-search huggingface dataset:
Phase II trial of triple-receptor tyrosine kinase receptor inhibitor nintedanib (BIBF 1120) in recurrent high-grade gliomas.
Authors: Andrew David Norden, David Schiff, Manmeet Singh Ahluwalia, Glenn Jay Lesser, Lakshmi Nayak, Eudocia Quant Lee, Alona Muzikansky, Jorg Dietrich, Katrina H. Smith, Sarah C. Gaffey, Christine Sceppa McCluskey, Keith L. Ligon, David A. Reardon, Patrick Y. Wen
Journal: Journal of Clinical Oncology (2013)

TPS2104 Background: Bevacizumab is the standard of care for patients with recurrent high-grade glioma (HGG). However, with current treatment options the median duration of response is only approximately 4 months. Potential mechanisms of resistance include upregulation of fibroblast growth factor (FGF) and increased pericyte coverage mediated by platelet-derived growth factor (PDGF). Nintedanibis an oral, small-molecule tyrosine kinase inhibitor of PDGFR α/β, FGFR 1/3, and vascular endothelial growth factor receptor (VEGFR) 1-3 that may overcome the problem of resistance to prior anti-VEGF therapy. Methods: This is an open-label, phase II trial in adults with first or second recurrence of HGG, stratified by prior therapy with bevacizumab. The primary endpoint is 6-month progression-free survival (PFS6) in the bevacizumab-naive arm and PFS3 in the post-bevacizumab arm. A Simon two-stage design is employed. Although the glioblastoma (GBM) comparison is the one of primary concern, 10 anaplastic glioma (AG) participants will be accrued to each arm in exploratory cohorts. Results: Nine of 40 GBM patients and 10 of 10 AG patients have been accrued in the bevacizumab-naive arm. Data in this arm are maturing. In the post-bevacizumab arm, 14 patients have been accrued, 10 of whom had GBM (71%). There were 11 men (79%), median age was 52 years (range 32-70), and median KPS was 90 (range, 60-100). One patient with anaplastic astrocytoma was not evaluable for response analysis because of early withdrawal of consent. There have been no responses. Two patients (1 with GBM and 1 with anaplastic oligodendroglioma) achieved stable disease. Median PFS was 28 days (95% CI: 27-28), and maximum PFS was 56 days. Median OS was 57 days (95% CI: 29-155). The post-bevacizumab arm was stopped after stage 1. Treatment was well tolerated, with limited Grade 3 liver function test abnormalities (n = 3), abdominal pain (n = 1), and hypertension (n = 1). Grade 1-2 adverse events also included diarrhea, nausea/vomiting, fatigue, and bleeding. Conclusions: Despite limited toxicity, nintedanibis ineffective in the cohort of recurrent HGG patients who failed bevacizumab. Updated results in the bevacizumab-naive arm will be presented. Clinical trial information: NCT01380782.
Comparison of discontinuation, health care resource utilization (HRU), and costs between metastatic breast cancer (mBC) patients (pts) who received trastuzumab (T) in an office clinic versus outpatient hospital setting.
Authors: Melissa Brammer, Deepa Lalla, Geneviève Gauthier, Annie Guérin, Philippe Giguere-Duval, Eric Q. Wu, Eduardo Santos
Journal: Journal of Clinical Oncology (2013)

642 Background: T treatment for mBC may be administered in an office clinic or outpatient hospital setting. This study assesses the impact of the site of care on T discontinuation risk, HRU, and costs. Methods: Adult women with mBC who received ≥2 T infusions in an outpatient hospital or office clinic setting were selected from the US-based Humana database (2007-2012). Pts were required to be continuous eligible in their healthcare plan for ≥6 months prior and ≥2 months following the first T infusion (index date). Pts were classified, based on their index site of care, into one of the following cohorts: 1) office clinic, or 2) outpatient hospital. Outcomes were measured from the index date up to the end of continuous eligibility/data availability, a change in the site of care, or 12 months after the index date, whichever occurred first. Treatment discontinuation (gap ≥45 consecutive days) was compared between cohorts using multivariate Cox-proportional hazards model. Monthly healthcare costs (2012 USD) and HRU were compared between cohorts using multivariate generalized linear/two-part models, and multivariate negative binomial regression models, respectively. Results: A total of 280 pts met the inclusion criteria; 64% and 36% in the office clinic and outpatient hospital cohort, respectively. Baseline characteristics were similar between cohorts. However, differences were found in terms of insurance plan type, year of index date and comorbid conditions (chronic pulmonary disease and peripheral vascular disorder). After adjusting for confounding factors, the outpatient hospital cohort had a 1.5 time higher risk of treatment discontinuation (p=.043) and incurred an incremental monthly cost of $1,954 (p=&lt;.001), mainly driven by higher office clinic and outpatient hospital costs ($1,483 p=.016). No differences were observed in HRU. Conclusions: Pts in the office clinics cohort were less likely to discontinue T and were associated with lower monthly total healthcare costs. Future research should examine the impact early discontinuation may have on clinical outcomes.
Evaluation of cabazitaxel's toxicity and tolerance: AC Camargo Cancer Center experience.
Authors: Christiane Silveira Marinho Albuquerque, Jose A. Rinck, Tatiana Vieira Costa, Camila Nassif Martins Ferreira, Aldo A. Dettino, Ingrid Hariman Fonseca Cunha, Vinicius Fernando Calsavara
Journal: Journal of Clinical Oncology (2017)

e566 Background: Cabazitaxel is an approved second-line treatment in metastatic castration-resistant prostate cancer therapy with a significant survival benefit compared to mitoxantrone. There are few data about cabazitaxel's toxicity in patients not selected. Objective: Evaluate the efficacy and toxicity among younger (&lt; 70 years) and older (&gt; 70 years) population. Methods: We selected 62 patients with metastatic castration resistant prostate cancer treated in AC Camargo Cancer Center from January 2011 to July 2015. 58 patients fulfilled the study criteria: diagnosis of adenocarcinoma prostate cancer, at least one session of cabazitaxel, with more than 18 years old. Results: We had in our sample 33 patients less than 70 years and 25 over 70 years. The initial dose of cabazitaxel was 25 mg/m 2 in 75.8% of patients &lt; 70 years and 52% in &gt; 70 years patients. The use of granulocytics growing factor was observed in 64% of the older patients and more than 80% of this indication was in primary profilaxis. There were five deaths associated to the treatment, 4 lung infection and 1 kidney failure. The worst grade of adverse event up to 30 days after last administration was grade 2, including hematological and non-hematological events, both with no statistical significance between the groups. However, there was a greater number of febrile neutropenia in elderly people (28% versus 6%) with a statistical significance between &lt; 70 e &gt; 70 years (p 0.031). OS was 13,7 months (IC 9.16 – 18.2) and PFS was 4,6 months (IC 3.43 – 5.73). OS among the two groups was lower in &lt; 70 years reaching 9,3 months (IC 2.06-16.5) versus 22.2 months (IC 4.86-39.50 ), p= 0.073. As well, PFS in &lt; 70 years was 3.8 months (IC 3.26-4.36) versus 4.6 months (IC 2.4-14.1), p = 0.02. Conclusions: Treatment with cabazitaxel is tolerable, with manageable adverse events in a real-world patient population. In our cohort, elderly population (&gt; 70 years) had more febrile neutropenia, suggesting dose reduction in this population, indication of granulocytic growing factor as primary profilaxis, close monitoring, and adequate patient counseling.
Identification of Novel Molecular Markers for the Follow-up of Minimal Residual Disease in Hematooncological Disorders
Authors: David Warren Hardekopf, Tereza Jancuskova, Marie Jarosova, Lucie Krutilkova, Radek Plachy, Lenka Zejskova, Radek Cmejla, Jan Vydra, Tomas Kozak, Michal Karas, Vladimir Koza, Alzbeta Zavrelova, Pavel Zak, Lukas Smolej, Sona Pekova
Journal: Blood (2011)
Large retroperitoneal lymph nodes (RPLN) as a novel risk factor for venous thromboembolism (VTE) in germ cell tumor (GCT) patients (pts) receiving first-line chemotherapy (chemo).
Authors: Ben Tran, Michel S Beausoleil, Eitan Amir, Michael A Jewett, Jeremy F. G. Sturgeon, Lynn Anson-Cartwright, Peter W. M. Chung, Padraig Richard Warde, Eric Winquist, Malcolm J. Moore, Philippe Bedard
Journal: Journal of Clinical Oncology (2012)

4535 Background: VTE causes substantial morbidity and mortality in GCT pts. The Khorana model is a validated predictive model that stratifies VTE risk in cancer pts receiving chemo; Khorana score ≥3 (K3) identifies pts at high risk. Many GCT pts have bulky RPLN that can cause venous stasis in the lower limbs. This study examines the incidence of VTE in GCT pts and assesses large RPLN as a novel predictor of VTE risk. Methods: Retrospective data from the Princess Margaret Hospital GCT database was complemented by review of medical records. GCT pts receiving 1st line chemo between 2000-2010 were included. Pts diagnosed with VTE prior to chemo and pts receiving thromboprophylaxis (TP) were excluded. Pts diagnosed with VTE during or within 3 months of completing chemo were identified. Large RPLN were defined as having maximal diameter ≥5cm. Odds ratios for VTE risk with large RPLN and K3 were calculated. Discriminatory accuracy (DA) of each predictor was calculated using area under the receiver operating characteristic curves (AUROC). An external cohort from London Regional Cancer Program, with similarly collected data, was used to validate results. Results: In the test cohort 21 (10%) of 216 pts developed VTE. Both large RPLN (OR 6.2, p&lt;0.001) and K3 (OR 11.8, p&lt;0.001) were significantly associated with VTE. Positive predictive value (PPV) was lower for large RPLN compared to K3 (21% v 44%, p&lt;0.014) but sensitivity was greater (71% v 40%, p=0.001), while DA showed no difference (AUROC 0.73 v 0.67, p=0.46). In the validation cohort 10 (9%) of 111 pts developed VTE. There was a non significant trend for associations between VTE and both large RPLN (OR 2.54, p=0.16) and K3 (OR 4.5, p=0.13). When compared to K3, sensitivity was greater for large RPLN (60% v 20%, p=0.003), but there was no difference in PPV (14% v 29%, p=0.25) or DA (AUROC 0.61 v 0.57, p=0.72). Conclusions: VTE occurs in 1 in 10 GCT pts receiving curative chemotherapy. Large RPLN is a novel and clinically applicable predictor of VTE risk, although prospective validation would be beneficial. Randomized controlled trials of TP in GCT pts should be considered in pts at high risk of VTE, identified by large RPLN or K3.
Improved survival for ovarian cancer patients stage IIIC treated at the Norwegian Radium Hospital between 1984 - 2001
Authors: C. Trope, H. Oksefjell, B. Sandstad
Journal: Journal of Clinical Oncology (2007)

16044 Background: The aim of this study was to evaluate the treatment of FIGO stage IIIC patients who were primarily treated completely or partially at the Norwegian Radium Hospital (NRH) during a 15-year period in order to discover possibilities for improvement of prognosis of advanced ovarian cancer. Methods: A retrospective study based on record information from all patients with epithelial ovarian cancer stage IIIC treated at NRH 1985 - 2000, in total 776 patients. Results: We found age, amount of residual tumour after surgery for primary treatment and type of chemotherapy to be the most significant prognostic factors for overall survival. During the last 5-year period primary surgery was increasingly centralised, surgery was improved with lymph node staging and paclitaxel was used. Survival was significantly best during the last 5-year period and after macroscopically radical surgery. Also progression-free survival was best with no macroscopic tumour left. Conclusions: Improved survival during the last 5-year period is partly attributed to improved surgery, partly to the addition of paclitaxel. We believe that a further centralisation of primary surgery for advanced ovarian cancer can contribute towards a better prognosis. No significant financial relationships to disclose.
Impact of rituximab on outcome of autologous transplantation for mantle cell lymphoma
Authors: A. Naing, J. Palmer, N. Tsai, N. Kogut, L. Popplewell, R. Rodriguez, A. Krishnan, R. Nakamura, S. J. Forman, A. Nademanee
Journal: Journal of Clinical Oncology (2006)

7555 Background: Currently, Mantle Cell Lymphoma (MCL) is an incurable disease. Patients treated with chemotherapy alone experience only transient responses, with no long-term improvement in disease-free/overall survival. While autologous hematopoietic stem cell transplantation (ASCT) in MCL patients has demonstrated prolonged survival, relapse remains the major issue. We evaluate the impact of rituximab (Rituxan, Rtx) on relapse and survival following ASCT. Method: A case-series of 83 MCL patients treated with ASCT at City of Hope (from 02/1991 to 04/2005) were examined; a total of 52 patients received Rtx (with-Rtx) as part of their induction/salvage treatment (pre-ASCT) and/or maintenance therapy (post-ASCT), 31 patients did not receive Rtx (no-Rtx) at any point pre-/post-ASCT. An assessment of baseline patient and disease characteristics (gender, age, KPS, % of pts with bone marrow involvement at diagnosis, disease stage/status at ASCT, % of pts with bulky disease B-symptoms at ASCT, and # of regimens administered prior to ASCT) showed no significant differences among the two groups. Result: To date, 23 patients have relapsed/progressed post-ASCT; 61% of the patients in the no-Rtx group remain disease free at last contact, while 79% in the with-Rtx group remain disease free. The median survival in the no-Rtx group is 77.63 months; the median survival time point for the with-Rtx group has not been reached due to shorter follow-up period. The 2-yr relapse rate for the with-Rtx/no-Rtx groups among 1st CR/PR patients were 19% (95% CI: 10–33%) and 26% (95% CI: 14–43%) (p &gt; 0.05) respectively and the 2-yr relapse rate for the with-Rtx/no-Rtx groups among the beyond 1st CR pts were 33% and 40% respectively (p &gt; 0.05). The survival endpoint showed similar results. The 2-yr survival probability for the with-Rtx/no-Rtx groups among the 1 st CR/PR patients were 91% (95% CI: 76–97%) and 82% (95% CI: 64–91%) (p &gt; 0.05) respectively and the 2-yr survival probability for the with-Rtx/no-Rtx groups among the patients beyond 1st CR/PR were 59% and 63% respectively (p &gt; 0.05). Conclusion: Using Rtx as induction/salvage and/or maintenance before and after ASCT therapy may not be associated with decreased relapse and improved survival. Nevertheless, our data indicate that outcome is better when ASCT is carried out at 1st CR/PR. No significant financial relationships to disclose.
A combination of cisplatin and irinotecan against advanced biliary tree carcinomas
Authors: R. Romano, D. Bilancia, A. M. Dello Russo, A. Di Nota, D. Germano, G. Rosati, L. Manzione
Journal: Journal of Clinical Oncology (2004)

4145 Background: In this clinical experience, still ongoing, we have treated 16 patients with advanced biliary tree carcinomas with Cisplatin and Irinotecan to assess its efficacy and feasibility. Methods: The elegibility criteria were: histologically proven biliary cancer with measurable metastatic lesions, unresectable cancer, age of 75 years or younger, performance status of 2 or less, one or no prior chemotherapy regimens, adequate bone marrow, liver, renal, and cardiac functions, and written informed consent. The treatment consisted of CDDP (30mg/mq) and CPT11 (150mg/mq) on day 1 and day 14, repeated every 4 weeks. The treatment was performed for 6 time or until progression disease and/or toxicity Results: 16 patients (11F, 5M), median age 69 (50–75), PS 0 25% (4/16), PS 1 75% (12/16), 50% stage III, 50% stage IV, were enrolled in this study. 3 (18%) patients are still in treatment. 5 (31%) patients came-off protocol for progression disease. Five patients had obtained partial remission, one patient complete remission and 2 patients disease progression. The severe adverse events (grade 3 or 4) was not frequents. Grade 3–4 neutropenia was observed in 3 patients (23%), nobody has grade 3–4 diarrhoeas. Other adverse reactions were mild. No treatment-related deaths occurred. Conclusions: The advanced or metastatic biliary tree carcinomas have a very poor prognosis. This combination of CDDP and CPT11, considered to be active against biliary cancer (overall response was 37%) with acceptable toxicity, should be further assessed in the future trials. No significant financial relationships to disclose.
Tolerability and activity of combinations of the PI3Kδ inhibitor idelalisib (GS-1101) with rituximab and/or bendamustine in patients with previously treated, indolent non-Hodgkin lymphoma (iNHL): Updated results from a phase I study.
Authors: John Leonard, Nina D. Wagner-Johnston, Steven E. Coutre, Ian Flinn, Marshall T. Schreeder, Nathan Hale Fowler, Jeff Porter Sharman, Ralph V. Boccia, Jacqueline Claudia Barrientos, Kanti Roop Rai, Thomas E. Boyd, Richard R. Furman, Leanne Holes, David Michael Johnson, Yeonhee Kim, Roger D. Dansey, Wayne R. Godfrey, Sven De Vos
Journal: Journal of Clinical Oncology (2013)

8500 Background: PI3K-delta signaling is critical for activation, proliferation and survival of B cells, and is hyperactive in many B-cell malignancies. Idelalisib is a first-in-class, selective, oral inhibitor of PI3Kδ that has shown considerable monotherapy activity in recurrent iNHL (Kahl, ICML 2011), as well as combination therapy (Fowler, ASCO 2012). Methods: This phase I study evaluated the activity of continuous (48 weeks) idelalisib (Id), 100/150 mg BID, in combination with rituximab (R) (375 mg/m 2 weekly x 8 doses) (Id+R), with bendamustine (B) (90 mg/m 2 x 2, for 6 cycles) (Id+B), or in combination with R (375 mg/m 2 monthly x 6) and B (90 mg/m 2 x 2), for 6 cycles (Id+BR). Investigators assessed response according to standard criteria (Cheson 2007). Patients who continued to benefit were able to enroll on an extension study. Results: Study enrolled 78 pts with relapsed/refractory iNHL, with 34 (44%) pts continuing on treatment in the ongoing extension protocol. The 3 cohorts included Id+R (N=30), Id+B (N=34), and Id+BR (N=14). Pts were 67% male, median age [range] of 62 [37E84] years, 41% with refractory disease, 88% stage III/IV, and 36% of FL with high FLIPI scores. The median [range] number of prior therapies was 3 [1E10]. The median [range] duration of treatment was 10.6 [0.5-29.2] months. Overall response rate (ORR) was 63/78 (81%), with 22/78 (28%) CR. The ORR/CR for Id+R was 77%/20%, Id+B was 85%/29%, and Id+BR was 79%/43%. At 20 months, the PFS was 66%. For responders, 73% were progression-free at 20 months. Most common adverse events included (total%/≥G3%) pyrexia (56/4), fatigue (45/4), nausea (41/0), rash (40/8), cough (37/0), diarrhea (36/8), chills (18/0), URI (18/1), and pneumonia (17/15). Lab abnormalities included (total%/≥G3%) ALT/AST elevations (56/17). Conclusions: Idelalisib-based combination therapy is highly active and well tolerated in patients with relapsed/refractory iNHL. These data support further clinical development. Phase III trials evaluating the efficacy of idelalisib in combination with R, or BR in iNHL are ongoing (NCT01732913, NCT01732926). Clinical trial information: NCT01732913, NCT01732929.
Generation of a prognostic cancer stem-like gene expression signature in men undergoing radical prostatectomy for localized prostate cancer.
Authors: Adrian Stuart Fairey, Dongyun Yang, Susan G. Groshen, David I. Quinn, Philip Kim, Navneet Virk, Lina Wang, Sue Ellen Martin, Craig Stephens, Amir Goldkorn
Journal: Journal of Clinical Oncology (2012)

4563 Background: Novel biomarkers are needed to predict recurrence after radical prostatectomy for localized prostate cancer. Recent data suggest that cancer stem-like cells (CSC) are present in prostate tumors, and the CSC phenotype has been associated with an aggressive cancer phenotype. We investigated whether tumor mRNA levels of genes typically expressed by CSC are associated with disease recurrence. Methods: Clinically annotated prostatectomy specimens (FFPE) were used for this nested case-control study. Samples represented men who underwent radical prostatectomy and either experienced a recurrence (PSA or clinical; n=152) or no recurrence (controls; n=124) with minimum 5-year follow-up. Men were excluded if they received neoadjuvant hormone therapy. Cases and controls were frequency matched based on D’Amico risk group. Laser capture microdissection with mRNA extraction and quantitative RT-PCR were used to quantify the expression of 12 candidate CSC-associated genes (ALDH1A1, Axin2, Bmi1, CD133, CD44a, CTNNB1/β-catenin, ITGA2/integrin α2, NANOG, Nkx3-1, Notch1, OCT 4, TACSTD2/Trop2). Univariable and multivariable analyses were conducted to measure associations with recurrence. Results: mRNA data were evaluable for 241 of 276 patients. Univariate Wilcoxon analysis showed that 4 genes (Axin2, p&lt;0.001; CD44a, p=0.036; OCT 4, p=0.017; TACSTD2, p=0.008) were expressed at low levels in tumors of patients whose disease recurred. Recursive partitioning analysis identified 3 genes significantly predictive of disease recurrence (Axin2, NANOG, CTNNB1), with cutpoints yielding odds ratios (OR) of 8.5 (Axin2 low /NANOG high ; n=94, 95%CI 3.7-19.2) and 5.1 (Axin2 low /NANOG very high /CTNNB1 low ; n=26, 95%CI 1.7-14.8). Conclusions: We identified a novel CSC-associated 3 gene expression signature with the potential to predict recurrence after radical prostatectomy. Axin2 is known to interact with CTNNB1/β-catenin in the Wnt signaling pathway, which in turn has been shown to regulate expression of NANOG, a key protein that mediates pluripotency. In vitro experiments and an independent cohort validation study are planned based on these novel findings.