tbuckley/cabot-search huggingface dataset:
Frequency and characteristics of cancer-related drowsiness (CRD or excessive daytime sleepiness) in patients with advanced cancer: Results of a prospective survey at a tertiary cancer center.
Authors: Sriram Yennu, Dave Balachandran, Sandra L. Pedraza, Elyssa A Berg, Gary B. Chisholm, Akhila Sunkepally Reddy, Janet L. Williams, Eduardo Bruera
Journal: Journal of Clinical Oncology (2014)

131 Background: CRD is extremely distressing but treatable symptom to the advanced cancer patients (ACP). There are limited studies to evaluate the frequency and characteristics of CRD. The aim of this study was to identify the frequency, and factors associated with severity of CRD. Secondary aim was to determine the screening performance Edmonton Symptom Assessment Scale (ESAS)-drowsiness item against the Epworth Sleepiness Scale (ESS). Methods: We prospectively assessed 180 consecutive ACP at a tertiary cancer hospital. After obtaining signed consent, the patients completed ESAS, Pittsburgh Sleep Quality Index (PSQI), Insomnia Severity Index (ISI); ESS (≥10 diagnostic of CRD), Hospital Anxiety Depression Scale (HADS), STOP-Bang Screening Scale (SBS), and Screening tool for RLS. We determined epidemiological performance, spearman correlations, regression analysis, receiver operated characteristics of CRD. Results: Of the180 patients assessed, 51% were female, CRD was found in 50% ACP, median scores(IQR) ESS: 11(7-14); ESAS- drowsiness item was 5 (2-6); PSQI was 8(5-11); ISI (13 (5-19); SBS 3(2-4); HADS-D 6(3-10). Sleep apnea was found in 61%; and RLS in 38%. ESAS-D was associated with other ESAS items[r, p-value] Sleep (0.38, &lt; 0.0001); pain (0.3, &lt; 0.0001); fatigue(0.51, &lt; 0.0001); depression(0.39, &lt; 0.0001); anxiety(0.44, &lt; 0.0001); shortness of breath(0.32, &lt; 0.0001); anorexia(0.36, &lt; 0.0001), FWB(0.41, &lt; 0.0001), and ESS (0.24, 0.001), Opioid dose [MEDD] (0.19, 0.01). Multivariate analysis found no independent predictors except ISI (OR 2.35; 0.036), ESAS Fatigue (OR 9.08, &lt;0.0001), ESAS Anxiety (3.0, 0.009); feeling of well-being (OR 2.27, p=0.04). An ESAS- drowsiness cut-off score of ≥ 3(of 10) resulted in a sensitivity and specificity of 81% and 32% and of 70% and 44% in the training and validation samples, respectively. Conclusions: Clinically significant CRD was associated with increased fatigue, anxiety, sleep disturbance and worse feeling of well-being. These symptoms should be routinely assessed and treated in ACP with CRD. ESAS-drowsiness score of ≥3 of 10 is most useful for screening CRD.
Genes differentially expressed in breast cancer (BC) samples as compared to normal breast tissue from women without cancer
Authors: M. A. Koike Folgueira, D. M. Carraro, H. Brentani, E. M. Barbosa, M. Mourao Netto, C. T. Oliveira, J. R. F. Caldeira, F. A. Soares, L. P. Camargo, M. M. Brentani
Journal: Journal of Clinical Oncology (2004)

9593 Background: We have determined the gene profile correlated to doxorubicin resistance in 38 BC patients (pt) treated with primary chemotherapy and 37 genes were differentially expressed in tumors according to response. Among the genes more expressed in sensitive tumors as compared to resistant tumors were ephrin receptor and c-src; JunD; and CDKN2B. Genes more expressed in resistant tumors were fibroblast growth factor receptor 2 and lymphocyte protein TK; Max (Myc partner); and MMP12 (metalloproteinase). We have now analyzed gene expression of these 38 tumors as compared to normal breast tissue (perilesional) obtained from 5 women without cancer submitted to resection of benign lesions. Methods: A tissue specific cDNA microarray glass slide was assembled based on genes expressed in mammary tissue and BC. Genes hyperexpressed in BC as determined in SAGE libraries were also selected. Sequences representing 496 genes and 195 ESTs were chosen in an ORESTES (open reading frame expressed sequence tags) bank (Instituto Ludwig de Pesquisa sobre o Câncer/FAPESP) or synthesized in PCR reactions and spotted 3 or 6 times on glass slides. Tissue was hand dissected, RNA was extracted, amplified, and co-hybridized with a HB4A (normal mammary epithelial cell line) probe against cDNA microarray slides. Results: Median age of BC pt was 51 y; pt were clinically staged as IIA (3), IIB (2), IIIA (17), IIIB (15) and IV (1 pt). Sixty three molecules were differentially expressed between tumors and normal breast tissue. Genes more expressed in tumors included KRT8 and KRT19 (cytoskeleton proteins); MMP11 and MMP12; transmembrane 4 superfamily member tetraspan NET-7; NME2 (tumor suppressor gene); REL (oncogene); MSH2 (DNA repair); XIAP (inhibitor of apoptosis) associated factor 1. Genes more expressed in normal tissue were CCND3 (cyclin D3); KRT14 and KRT15; LAMA3 and LAMB3 (laminin); maspin (proteinase inhibitor); GSTP1 (detoxifying enzyme); ITGB4 (adhesion molecule); JUN, FOS, MYC (transcription factors) and MAX; and ABCG2 (ATP binding cassette). Conclusions: This gene profile seems to characterize breast malignancy. Supported by FAPESP 01/00146–8 No significant financial relationships to disclose.
Pharmacodynamic and safety study of reolysin in patients with advanced solid tumors
Authors: R. Gollamudi, K. Desai, I. Chaudhary, M. H. Ghalib, B. Wong, M. Einstein, M. Coffey, G. Gill, S. Mani, S. Goel
Journal: Journal of Clinical Oncology (2007)

14004 Background: Reolysin is an intravenous formulation of reovirus serotype 3 - Dearing strain which is a double stranded RNA non-enveloped icosahedral virus capable of inducing cytopathic effects in cancer cells that have an activating mutation in the ras protooncogene. Pre clinical testing has identified cancer cell lines as being susceptible to reovirus infection. Methods: This was an open- label single center phase I safety and dose escalation trial of reolysin administered intravenously over 1 hour on day 0 in a 28 day cycle. Dose escalations were in half log increments. Serum for neutralizing antibody (NA) was drawn at baseline, and days (d) 1, 7, 14, 21, and 28, and serum, stool, saliva, and urine for viral shedding (by RT-PCR) were sampled on d 1,7,14,21, and 28. Response was assessed by imaging studies after 1, 3, 5, and 7 cycles. Results: 18 patients (pt); median age 57 (40–72) years; performance status 0–1; diagnoses - ovarian (6), colorectal (5), and others (7) received 27 cycles of reolysin (median 1, range 1–7) in 6 dose cohorts of 1x10 8 , 3x10 8 , 1x10 9 , 3x10 9 , 1x10 10 , and 3x10 10 tissue culture infective dose (TCID) 50 . No protocol defined dose limiting toxicities were observed. Drug related grade 2 toxicities included chills (2 pt), and fatigue (3 pt). The only grade 3 event was fever in cycle 7 in a 57 year old woman with progressive breast cancer, treated at a dose of 1x10 10 TCID 50 . She was noted to have 28.5% shrinkage in objective tumor volume. An additional 7 pt had stable disease (SD). No NA was detectable in the serum in any pt at baseline; however all pt developed NA (on d 5 in 5 pt, d 8 in 11 pt, d 14 in 1 pt, and d 28 in 1 pt) during the course of the study. Viral shedding was observed in serum - 5 pt, stool - 3 pt, saliva - 3 pt, and urine - 4 pt. Of interest, 4 of 5 pt with viral shedding had SD as their best response. However, there was no observed relationship between NA formation and SD. Conclusion: Reolysin administered as a one hour infusion on a monthly schedule is safe and well-tolerated even in multiple doses. This preliminary data suggests there is anti-tumor activity of reolysin as a single agent, and warrants further studies either alone or in combination with cytotoxic chemotherapy. [Table: see text]
Primary nasopharyngeal non Hodgkin lymphoma: A retrospective investigation of 26 patients
Authors: I. N. Nabil, W. Allam, K. Alaoui, H. Errihani
Journal: Journal of Clinical Oncology (2009)

e19552 Background: Primary nasopharyngeal non-Hodgkin lymphoma (NNHL) was uncommon. In this retrospective study we report our experience dealing with this disease at the National Institute of Oncology. Methods: We retrospectively analyzed various characteristics of Primary NNHL: patient demographics, clinical and histological diagnosis, disease stage, treatment effects and outcome, in 26 patients treated at our institution between January 2001 and December 2007. Results: The average age of our patients was 52.7 years (range: 31 - 87 years). The male/female ratio was equal to 1.5/1. The major symptoms at first diagnosis were: nasal obstruction (88.6%), hypoacousia (88.4%), epistaxis (33.3%) and rhinorrhea (15.3%). Clinical examination founded bilateral cervical lymph nodes in 17 cases (65%). Histological analysis showed follicular lymphoma in 7 cases (26.9%), large B-cell lymphoma in 11 cases (42,3%) and T lymphoma in 4 cases ( 15,3%). Four (15.4%) of the patients were at stage I, 15 (57.6%) were at stage II, and 7 (27%) were at stage III/IV. At early stage, the patients were managed with chemo-radiotherapy and were managed with CHOP based chemotherapy at advanced stage. At the end of total treatment, 18 patients (69.2%) achieved complete response and remained disease free while 4 (15.4%) achieved partial response (&gt;70%) and 4 (15.4%) were progressive (these patients received second line chemotherapy). After 110 months median flow-up, median disease free and overall survival were not reached. Overall, the treatment was well tolerated. Conclusions: From our study and from the literature, we conclude that histological characteristics, principle of treatment and outcome of primary NNHL patients are similar to that of patients with nodal lymphoma. No significant financial relationships to disclose.
Evaluation of paclitaxel and dacarbazine combination in metastatic melanoma
Authors: L. N. Minea, R. Anghel, L. Oprea, T. Georgescu, X. Bacinschi
Journal: Journal of Clinical Oncology (2008)

20005 Background: Metastatic melanoma has a poor prognosis, with less than 11 months median survival rate from the diagnosis of distant metastasis. Response rates for both dacarbazine and paclitaxel as single therapy are around 20%. High levels of S100 protein were found in the serum of patients with metastatic melanoma. Methods: The purpose of this study was to determine the safety and efficacy of Paclitaxel + Dacarbazine combination in metastatic malignant melanoma. Secondary we want to evaluate the correlation between serum level of S100 protein and therapeutic response. 63 patients were included between January 2005 and December 2006. The median age was 54 years. Patients could have prior adjuvant immunotherapy. Performance status was ECOG 0 - 2. Metastatic sites were: liver - 29 patients; lung - 19 patients; soft tissue - 11 patients; lymph nodes - 9 patients; bone - 6 patients. Treatment schedule: Paclitaxel 175 mg/sqm on day 1 and Dacarbazine 400 mg/sqm/day on days 1, 2, repetead at 3 weeks for six cycles. Serum S100 was determined at start, every two chemotherapy cycles, and in follow-up visits (every three month). Results: All patients were evaluable for toxicity and 61 patients were evaluable for efficacy. Main grade 3–4 toxicity was: hematology 12 patients, no neutropenic fever, neuropathy 8 patients, emesis 9 patients. Overall response rate was 23.8% (15 patients partial response); 23 patients had stable disease and 25 patients had progressive disease. 59 patients had elevated S100 levels. The highest were among patients with liver metastasis. The responders registered decrease of more than 50% in S100 level. Conclusions: Our results suggest that the combination is not significant superior to single agent therapy. The regimen was well tolerated, with no treatment related serious adverse events. Serum levels of S100 were correlated with the treatment efficacy and could be used for easy follow-up. No significant financial relationships to disclose.
ECF can be used as adjuvant treatment for oesophagogastric adenocarcinoma: A two-institutions experience
Authors: P.-C. Saletti, D. Berthold, N. Fazio, E. Zucca, M. Ghielmini, S. Mauri, F. Cavalli
Journal: Journal of Clinical Oncology (2004)

4251 Background: Surgery is the cornerstone of curative therapy for operable oesophagogastric adenocarcinoma (OGAC), but the risk of recurrence is high in T3–4 and/or N+ disease. We report our experience using in the adjuvant setting the ECF regimen, a cytotoxic combination effective and widely used in advanced disease. Methods: Between November 1996 and February 2003, 45 patients with OGAC who underwent curative surgery were treated with ECF (Epirubicin 50 mg/m2 and Cisplatin 60 mg/m2 on day 1, 5-Fluorouracil 200 mg/m2/day as a continous infusion) every 3 weeks for 4–6 months. The median age was 59 years (range 32–74), and PS was â‰¤ 1 in all cases. Six patients had stage UICC IB, 11 stage II, 11 stage IIIA, 6 stage IIIB and 11 stage IV (T4 and/or N3). Surgery was partial gastrectomy in 51% and total gastrectomy in 44% of cases; D2 resection was performed in all cases. Results: The mean number of courses per patient was 4,7 (range 2 - 6). Delay of chemotherapy was necessary in 33% of cases; dose reductions were applied in 42%. Adverse events due to venous port device were 18%. At a median follow-up of 59,6 months, the median overall survival was 50,1 months. Relapse occurred in 24 patients (53%). One patient had local recurrence, distant metastases were seen in 23 patients. Twenty-one patients died of progressive disease. Chemotherapy was well tolerated, the main grade 3/4 toxicities being: neutropenia 47%, anorexia 11%, nausea and vomiting 6%, anemia and thrombocytopenia 4%. Port and deep venous thrombosis were seen in 6%. No grade 3/4 infection occurred, and there where no treatment-related deaths. Conclusions: ECF is safe and feasible in patients with locally advanced OGAC. The survival of our patients compares favorably with historical cohorts, supporting the possibility of using ECF in the adjuvant setting. Randomised studies are needed to confirm this hypothesis. No significant financial relationships to disclose.
Natural history and multimodality treatment of early hepatocellular carcinoma prospectively detected in cirrhotic patients under surveillance.
Authors: M. A. Manini, A. Sangiovanni, C. Della Corte, S. Vavassori, M. Iavarone, R. Romeo, M. Fraquelli, L.V. Forzenigo, A. Aghemo, M. Colombo
Journal: Journal of Clinical Oncology (2010)

e14574 Background: Surveillance with abdominal US of cirrhotic patients increases the identification of small hepatocellular carcinoma (HCC) to be treated with radical therapies. Aim: To define the treatment applicability and efficacy in de novo diagnosed HCC nodules according to BCLC criteria. Methods: Consecutive liver nodules (LN) detected in patients withChild-Pugh A cirrhosis under surveillance were investigated with contrast-enhanced ultrasound (CE-US), dynamic computed tomography (CT) and dynamic magnetic resonance (MR) and fine-needle biopsy (FNB). HCC were staged with chest CT scan, and bone scintigraphy, treated according to BCLC criteria, and followed with CT/MR at least every 3 months. EASL modified criteria were used to assess treatment response. Results: 84 consecutive de-novo liver nodules, including 12 US undetected revealed by CT/MR, (7 < 1 cm, 66 1-2 cm, 11 > 2 cm in size), were identified in 69 patients, mean age 65 years (43-84), 51 (74%) males. Forty-five patients had 51 HCC nodules, including 6 missed by US (5 < 1 cm, 38 between 1-2 cm, 8 > 2 cm). HCC was single nodule in 44 (98%) patients at US, decreasing to 40 (87%) after staging, all BCLC A. First line treatment was radio interstitial thermal ablation (RITA) in 26 (58%) patients, percutaneous ethanol injection ( PEI) in 9 (20%), resection in 8 (17%), transarterial chemoembolization (TACE) in 2 (4%). Complete response (CR) was achieved in 31 (69%) patients, partial response (PR) in 9 (20%), stable disease (SD) in 1 (2%) and progression (P) in 1 (2%), Three (7%) patients were lost to follow-up. OLT was performed in 4 (9%) patients after bridge therapy. During a mean follow-up of 21 (7-37) months, recurrence occurred in 3 (7%) patients and additional LN developed in 17 (36%) patients in liver segments other than the treated ones, including 3 HCC (mean annual incidence of 4.1%), 2 MRN, 1 non- Hodgkin lymphoma, 11 still undefined. HCC metastases developed in 3 (7%). Conclusions: Radical treatment of early HCC in cirrhotics under surveillance is applicable to 96% of the patients, to give overall CR rates of 69%), while OLT was performed in a minority (9%) of patients only. No significant financial relationships to disclose.
Schedule dependency of 5-fluorouracil (5FU) chemotherapy in patients with advanced colorectal cancer: A systematic review
Authors: E. Barrajon, G. Esquerdo, A. Lopez, C. Llorca
Journal: Journal of Clinical Oncology (2004)

2139 Background: Clinical schedules of chemotherapy have been based on preclinical biological and animal models. The concept of 'more is better' have brought higher response rate with more toxicity in general terms, leading to the concept of 'maximum tolerated dose'. The pharmacokinetic concept of 'area under the concentration-time curve' (AUC) have been tried to summarize the pharmacodynamic concept of 'dose-response relationship'. Nevertheless, different schedules with the same AUC may produce different patterns of efficacy and toxicity, as is the case for phase-specific agents such as 5FU. The goal of the present study is to apply mathematical models to clinical data on 5FU to explain efficacy and toxicity data which allow the search of optimal schedules. Methods: Clinical trials of 5FU single agent in advanced colorectal cancer have been searched in PubMed extracting data about schedule, response rate and percent of hematological toxicity, mucositis, diarrhea and dermatitis. Data have been analyzed by multivariate regression, as well as pharmacokinetic and cytokinetic analysis. Results: Eighty trials have been identified and included for analysis. Regression analysis shows optimal schedules of 5FU with intermittent doses of 1000–2000 mg/m(2) infused in 12–72 hours. A compartmental pharmacokinetic model points to the 'time above a threshold' as the main factor implicated in toxicity. An optimal interval between doses is suggested according to cytokinetic parameters Conclusions: These results should be taken in to account in the design of chemotherapy with multiple drugs and suggest new approaches to the use of the new oral fluoropyrimidines in combination No significant financial relationships to disclose.
Phase I study of sorafenib in combination with everolimus (RAD001) in patients with advanced neuroendocrine tumors (NET).
Authors: J. A. Chan, R. J. Mayer, N. Jackson, P. Malinowski, E. Regan, M. Kulke
Journal: Journal of Clinical Oncology (2010)

e14597 Background: Sorafenib and everolimus independently have been shown to have activity in NET. In light of potential synergy between VEGF pathway and mTOR inhibitors in this disease, we performed a phase I study to evaluate the safety and feasibility of combining sorafenib and everolimus in pts with advanced NET. Methods: Two cohorts of 3 or 6 patients (pts) with metastatic or inoperable NET were treated with oral everolimus 10 mg daily in combination with sorafenib (dose level 1: 200 mg BID; dose level 2: 200 mg in the morning, 400 mg in the evening) using a standard phase I dose escalation design. Treatment was continued until tumor progression, unacceptable toxicity, or withdrawal of consent. Results: All 9 enrolled pts were evaluable for toxicity. Enrolled pts had the following characteristics: M:F = 4:5; median age 56 (range 49-68); ECOG PS 0/1 = 5/4. All 9 pts had low-intermediate grade NETs (midgut n = 6; bronchial n = 2; gastric n = 1). Pts have received a median of 2 cycles of treatment (range 1-6). One pt in Cohort 1 experienced protocol- defined DLT (grade 3 skin rash); the cohort was expanded to 6 pts with no further observed DLT in the cohort. Other ≥ grade 3 treatment-related adverse events at dose level 1 included grade 3 thrombocytopenia (n = 2), grade 3 hypokalemia (n = 2), grade 3 hypophosphatemia (n = 1), grade 4 hypophosphatemia (n = 1), grade 4 hypocalcemia (n = 1). One pt treated at dose level 1 with gastric carcinoid tumor experienced fatal gastric perforation that occurred following the first cycle of therapy and therefore was not considered DLT. In the absence of additional DLT at dose level 1, enrollment to dose level 2 was initiated. All 3 pts in Cohort 2 experienced DLT (grade 3 thrombocytopenia requiring holding treatment for > 14 days, grade 3 hand-foot skin reaction, grade 3 skin rash/allergic reaction). Grade 3 hypophosphatemia (n = 1) was also observed at dose level 2. Independently-reviewed best objective responses in 5 evaluable pts in Cohort 1 revealed stable disease in all 5 pts. Conclusions: Sorafenib 200 mg po BID in combination with everolimus 10 mg po QD has been established as the MTD in pts with advanced NET. Further enrollment to evaluate safety and antitumor efficacy at this dose level is ongoing. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Bayer/Onyx, Novartis
Phase 2 study of cobimetinib in combination with vemurafenib in active melanoma brain metastases (coBRIM-B).
Authors: Melissa K. Yee, Yan Lin, Vikram C. Gorantla, Lisa H. Butterfield, Harriet M. Kluger, Paul B. Chapman, Tara C. Gangadhar, Mohammed M. Milhem, Anna C. Pavlick, Ravi K. Amaravadi, Lynn Mara Schuchter, Ahmad A. Tarhini, John M. Kirkwood, Hussein Abdul-Hassan Tawbi
Journal: Journal of Clinical Oncology (2015)

TPS9088 Background: Significant advances in the management of melanoma have improved the prognosis and overall survival of patients (pts) with metastatic disease. However, pts with active melanoma brain metastases (MBM) have been excluded from large Phase III trials and overall prognosis remains poor. Resistance to BRAF inhibitors (BRAFi) has been associated with reactivation of MAPK pathway and combination with MEK inhibitors (MEKi) has shown synergy and delays resistance. Cobimetinib is a potent MEK 1/2 inhibitor. In pts without MBM, the combination of vemurafenib + cobimetinib has improved response rates and PFS as compared to vemurafenib. Single agents BRAFi are safe to administer in pts with MBM resulting in objective intracranial responses. We aim to improve the outcomes of pts with MBM by assessing the clinical benefit of combination BRAFi/MEKi (vemurafenib + cobimetinib) in this population. Methods: This is a multi-center single arm, open label, Simon 2-stage Phase 2 study to determine the safety and efficacy of the combination of cobimetinib and vemurafenib in patients with BRAF-mutated melanoma with active MBM. Pts must have histologically confirmed BRAF V600-mutated metastatic melanoma and > 1 measurable intracranial target lesion. Prior BRAFi or MEKi is not allowed. Subjects will be given vemurafenib 960 mg PO BID and cobimetinib 60 mg PO QD for 21 days (28-day cycle). The primary objective is to determine the investigator-assessed objective intracranial response rate (OIRR) as measured by modified RECIST. The primary efficacy analysis is based on pts with BRAF V600E mutations and the study will accrue 29 pts in the 1st stage. If > 6 pts experience an OIRR, acrrual to the 2nd stage will proceed to a total of 72 pts. Pts with non-V600E mutation are allowed but will not enter into the primary efficacy analysis. Secondary objectives include safety/tolerability, ORR (intracranial + extracranial), PFS, OS, duration of response, changes in relative apparent diffusion coefficient by MRI, volumetric response using 3D-MRI in a subset of pts, immune modulation and early markers of progression in peripheral blood, and health-related quality of life (by FACT-Br). The trial is open for enrollement. NCT02230306 Clinical trial information: NCT02230306.