tbuckley/cabot-search huggingface dataset:
Phase I study of seliciclib (CYC202 or <i>R</i>-roscovitine) in combination with gemcitabine (gem)/cisplatin (cis) in patients with advanced non-small cell lung cancer (NSCLC)
Authors: W. S. Siegel-Lakhai, D. O. Rodenstein, J. H. Beijnen, A. Gianella-Borradori, J. H. M. Schellens, D. C. Talbot
Journal: Journal of Clinical Oncology (2005)

2060 Background: Seliciclib (CYC202 or R-roscovitine) is a potent inhibitor of cyclin dependent kinases including CDK2/cyclin E, CDK7/cyclin H and CDK9/cyclin T. Seliciclib showed activity in in vivo NSCLC xenografts and showed synergy when given in combination with gem. Gem + cis is a widely used combination in the first-line treatment of NSCLC. This trial aimed to determine the safety and the maximal tolerated dose (MTD) of seliciclib in combination with gem/cis in patients (pts) with NSCLC. Methods: Pts were enrolled into 3 cohorts: cohort 1-seliciclib 400 mg bid + gem 1000 mg/m2 / cis 75 mg/m2; cohort 2-seliciclib 800 mg bid + gem 1000 mg/m2/cis 75 mg/m2; cohort 3-seliciclib 1200 mg bid + gem 1000 mg/m2/cis 75 mg/m2. Seliciclib was administered on days 1–4, 8–11, 15–18; gem 30 min IV infusion on days 5 and 12; cis 2 hrs IV infusion on day 5, of a 21 day cycle. Treatment was for a maximum of 6 cycles. MTD was the highest dose of seliciclib that caused DLT in ≤ 2/6 pts. PK sampling was performed during cycle 1 to evaluate a possible influence of seliciclib on gem/cis blood levels and vice versa. PD sampling was performed during each of the 6 cycles. Results: 27 pts (11F/16M; median age 61, range 31–75) were treated (2 in cohort 1; 19 in cohort 2; 6 in cohort 3). DLTs: cohort 1–0/2; cohort 2–3/19; cohort 3–3/6. DLTs consisted of Grade 3 elevation of GGT, nausea, vomiting and transient hypokalaemia. Hypokalaemia recovered after cessation of treatment. Hematological toxicity was mild. Seliciclib PK parameters of pts treated in cohort 2 are determined. Gem/cis did not seem to affect the pharmacokinetics of seliciclib. 14/27 pts were evaluable for response to date: 6 PR, 7 SD and 1 PD giving a response rate of 42.9%.Conclusion: The MTD was determined as seliciclib 800 mg bid + gem 1000 mg/m2/cis 75 mg/m2. Enrollment continues at this dose level in a Phase II setting including PK/PD assessments. No significant financial relationships to disclose.
Serum-derived bovine immunoglobulin in the alleviation of irinotecan-induced mucositis.
Authors: Emma Hazel Bateman, Eric Weaver, Gerald Klein, Erin Plews, Anthony Wignall, Belinda Wozniak, Imogen White, Dorothy M. K. Keefe
Journal: Journal of Clinical Oncology (2014)

166 Background: Gastrointestinal (GI) mucositis is associated with diarrhoea and intestinal barrier dysfunction caused by apoptosis, immune dysfunction, and microbiome alterations. Serum-derived bovine immunoglobulin (SBI) has been shown to ameliorate inflammation in colitis models, has been shown to improve HIV-induced enteropathy and nutritional status, and is being investigated in post-surgical recovery in oncology patients. We investigated in a rat model whether SBI was effective in alleviating symptoms of GI mucositis. Methods: Animals were gavaged with 250 or 500mg/kg of SBI twice daily, before intraperitoneal administration of 200mg/kg irinotecan on day 4, and for 6 days post-irinotecan. Animals were monitored for bodyweight and diarrhoea. Tissues were collected at necropsy 6, 48, 96 and 144 hours post-irinotecan. H&amp;E-stained colon and jejunum were analysed for histological damage. Results: The overall incidence, severity and duration of diarrhoea, and clinical symptoms of mucositis, were decreased in irinotecan-treated animals that had received SBI. Animals receiving 500 mg SBI/kg also tended to lose less bodyweight than animals treated only with irinotecan (P&gt;0.10). Animals receiving SBI had less pronounced irinotecan-induced changes in neutrophil levels (P≈0.02), and lower tissue damage scores than those receiving irinotecan alone (P&lt;0.0001). Conclusions: Twice-daily oral gavage of SBI was well-tolerated, and reduced the incidence, severity and duration of irinotecan-induced mucositis. SBI was associated with less pronounced changes in inflammatory cell levels and intestinal tissue damage. Ongoing experiments aim to explore the mechanisms of SBI-associated gastrointestinal protection.
VEGF-Trap for patients (pts) with recurrent platinum-resistant epithelial ovarian cancer (EOC): Preliminary results of a randomized, multicenter phase II study
Authors: W. P. Tew, N. Colombo, I. Ray-Coquard, A. Oza, J. del Campo, G. Scambia, D. Spriggs
Journal: Journal of Clinical Oncology (2007)

5508 Background: Vascular endothelial growth factor (VEGF) is over-expressed in EOC and associated with poor prognosis. VEGF Trap, a potent angiogenesis inhibitor fusion protein, is comprised of portions of human VEGF-receptor R1+R2 (Flt-1, KDR) extracellular domains and fused to the Fc portion of human IgG. VEGF Trap binds VEGF-A and neutralizes all VEGF-A isoforms plus placental growth factor. Methods: This is a randomized, double blind, multicenter, 2-stage, phase II trial of VEGF Trap (2 or 4 mg/kg) administered intravenously every 2 weeks, in pts with recurrent EOC. Eligible criteria included 2 or 3 prior chemo regimens for advanced disease; platinum- resistance, topotecan- and/or liposomal doxorubicin-resistance; no prior VEGF inhibitor treatment; ECOG performance status 0–2; normal organ function; no proteinuria (&lt;500 mg/24hrs or UPCR =1); controlled blood pressure. This Simon 2 stage design, requires 3 responders out of 42 evaluable, in each arm to continue accrual into stage 2. Results: Across 62 centers in Europe, Canada and US, rapid accrual led to 162 pts randomized from 5/06 to 12/06. Median age: 58, PS (0,1,2): 56,40,4%. Of 45 pts currently in the database, across the two arms, adverse events included (any grade): headache (38%), fatigue (36%), dysphonia (33%), nausea (29%), asthenia (24%), diarrhea (18%), hypertension (16%), proteinuria (7%), renal dysfunction (4%). Grade 3–4, included: hypertension (9%), proteinuria (4%), encephalopathy (2%) and renal failure (2%). Of the 162 pts who had at minimum one cycle, study drug-related SAE include (N): thrombocytopenia (1), anemia (1), headache (1) asthenia (2),dyspnea (1), hypertension (4), bowel perforation (2), encephalopathy (1), renal failure (2), proteinuria (1), phlebitis (1) and pulmonary embolism (1). 5 partial responses (11%) have been reported. Conclusions: VEGF Trap has activity in this heavily-pretreated EOC population. The first stage of accrual is complete and updated results will be presented. No significant financial relationships to disclose.
Factor analysis in early detection of malignancies
Authors: A. F. Lazarev, V. D. Petrova, T. V. Sinkina, I. A. Selezneva, S. A. Terekhova
Journal: Journal of Clinical Oncology (2006)

1033 Background: The existing methods of forecasting of malignancies and forming o of increased oncological risk groups are unserviceable for practical use because of their low reliability (no more than 84%). Methods: There was elaborated an original method for forming of increased oncological risk groups with reliability of 95%. It is based on factor analysis, including the data of phenotypes and genotypes, anamnesis, laboratory testing with further computer processing. The result lies in determination of a factor number. Its quantity forms figures of oncological risk rate. The dependence of risk rate on the quantity of a factor number is ascertained on the basis of data of more than 10000 observations ( table ). The patients with risk rate more than 80–90% are subjected to complex examination according to the elaborated algorithms. In case of absence of clinical symptoms of this or that organ lesion, each-organ search is being made in order to detect malignant neoplasms in accordance with their frequency on the territory of Altai region. Results: There were examined 4775 patients who happened to be in the zone of radioactive influence of Semipalatinsk nuclear testing ground (aged 43 years - 83 years old): male - 1639, female - 3136. 191 (4.0%) cases of cancer were detected: thyroid gland cancer - 56 cases, mammary gland cancer - 23, skin cancer - 49, uterine cervix cancer - 14, stomach cancer -11, lungs cancer -11, others -27. 5 cases of cancer in situ were revealed. Specific gravity of early forms of cancer was 96.5%. Conclusion: The research proved high effectiveness of the elaborated method for increased oncological risk group formation. [Table: see text] No significant financial relationships to disclose.
Fluorescence-guided tumor resection using a telomerase-dependent adenoviral GFP for cancer-specific labeling.
Authors: H. Kishimoto, M. Zhao, K. Hayashi, Y. Urata, T. Fujiwara, M. Bouvet, R. M. Hoffman
Journal: Journal of Clinical Oncology (2010)

e13660 Background: Cancer surgery requires the complete and precise identification of malignant tissue margins including the smallest disseminated lesions and is therefore often unsuccessful. Methods: Introducing and selectively activating the green fluorescent protein (GFP) gene in metastatic cancer in mouse models is made possible by the development of OBP-401, a telomerase- dependent, replication competent adenovirus expressing GFP. Results: This potentially powerful adjunct to surgical navigation was demonstrated in 2 nude mouse models that represent difficult surgical challenges—the resection of widely disseminated cancer. HCT-116, a model of intraperitoneal disseminated human colon cancer, was labeled by virus injection into the peritoneal cavity. A549, a model of pleural dissemination of human lung cancer, was labeled by virus administered into the pleural cavity. Only the malignant tissue fluoresced brightly in both models. In the intraperitoneal model of disseminated cancer, fluorescence-guided surgery enabled resection of all tumor nodules labeled with GFP by OBP- 401. Conclusions: The data in this report suggest that adenoviral-GFP labeling tumors can enable fluorescence- guided surgical navigation and has clinical potential. No significant financial relationships to disclose.
Cetuximab in recurrent/metastatic (R&amp;M) squamous cell carcinoma of the head and neck (SCCHN) refractory to first-line platinum-based therapies
Authors: J. B. Vermorken, J. Bourhis, J. Trigo, M. Kies, X. Leon, M. Mueser, N. Amellal, A. Schueler, J. Baselga
Journal: Journal of Clinical Oncology (2005)

5505 Background: Patients with R&M SCCHN have a poor prognosis. Patients failing first-line therapy have few therapeutic options. Cetuximab (Erbitux) is an IgG1 monoclonal antibody targeting the epidermal growth factor receptor (EGFR) which has shown second-line activity in SCCHN Methods: We present here a descriptive comparison of the intention-to-treat efficacy data from 330 patients treated with cetuximab (400 mg/m2 initial dose followed by 250 mg/m2/week) in 3 phase II studies (2 cetuximab plus platinum compound [at the same dose and schedule the patient progressed on] [n=96 and n=131] and 1 cetuximab monotherapy [n=103]) with historical data from a retrospective analysis in which 151 patients received various second-line treatments (Leon et al. Proc ASCO 2003). All patients had R&M SCCHN that had progressed on platinum-based therapy. Statistical analyses were not performed on these data. Results: The efficacy results are summarised in the table below. In all studies, cetuximab was well tolerated, the most common adverse event being skin reactions. In the monotherapy study, acne-like rash was reported in 69% of the cases (Grade 3/4 in 1%). When cetuximab was combined with platinum, acne-like rash was reported in 72%of the patients (Grade 3/4 in 3%). Severe hypersensitivity reactions were seen in between 0 and 3% of patients in the three studies. Conclusions: The median survival time of around 6 months achieved with cetuximab in platinum-refractory SCCHN is similar to that seen with first-line therapy and represents an increase in survival of 2.5 months compared with platinum-refractory historical controls. Based on these results cetuximab monotherapy seems to be a good option in patients with recurrent/metastatic SCCHN who have progressed on platinum-based chemotherapy. No significant financial relationships to disclose.
Abstract 16935: Hyponatremia in Children Hospitalized with Decompensated Heart Failure: Prevalence, Severity and Association with Clinical Outcome
Authors: Jack Price, Kevin Chiou, Jonathan Hanna, Jason Goldberg, Timothy Humlicek, Joseph Hagan, Antonio Cabrera, Aamir Jeewa, Susan Denfield, William Dreyer, Ayse Arikan
Journal: Circulation (2014)

Introduction: Hyponatremia occurs commonly in adults with heart failure (HF) but its prevalence, severity and clinical impact are not known in children. Hypothesis: Hyponatremia is associated with adverse clinical outcomes in children hospitalized with HF. Methods: Consecutive patients (pts) from a single institution who required hospitalization for treatment of acute decompensated heart failure were studied. Inclusion criteria: pts age 3 months to 21 years hospitalized for HF attributable to ventricular dysfunction. Exclusion criteria: acute graft rejection, disease of the central nervous system, HF attributable to left-to-right intracardiac shunts, cyanotic heart disease, treatment with vasopressin during hospitalization. Admission serum sodium (Na) concentration and lowest Na before the composite end-point or discharge were examined. The composite end-point was death, transplant or use of mechanical circulatory support. Results: One hundred forty-one patients met study criteria. Etiologies of HF includ...
Clinical implications of polymorphisms in UDP-glucuronosyl transferase (UGT) in patients with metastatic colorectal cancer (mCRC) who were treated with oxaliplatin, irinotecan, and S-1.
Authors: Sun Young Kim, Mi Song I Jang, Hyun Mi Kim, Ji Yeon Baek, Yong Sang Hong, Kyung Hae Jung
Journal: Journal of Clinical Oncology (2012)

503 Background: The three-drug regimen with oxaliplatin, irinotecan and fluoropyrimidine is an effective therapeutic option for patients with mCRC, but is associated with high rate of toxicity. Pharmacogenetic profile might be helpful for selection of proper patients for this intensive regimen. Methods: Forty-two patients were enrolled to our phase II trial and were given irinotecan 150mg/m 2 plus oxaliplatin 85mg/m 2 on D1 and S-1 80mg/m 2 /day on D1-14 every 21 days as their front-line therapy for mCRC. Genomic DNA was extracted from peripheral blood, where the presence of germline polymorphisms of UGT including UGT1A1*6, UGT1A1*28, UGT1A1*60, UGT1A6*2, and UGT1A7*3 were tested. Results: Patients with UGT1A1*6 allele had a tendency of more frequent grade 2-3 vomiting (p = 0.06) compared to those without UGT1A1*6. The presence of a haplotype containing UGT1A6*2 and UGT1A7*3 was associated with grade 2-3 vomiting (p = 0.014) and grade 2-3 diarrhea (p = 0.063). Higher objective response rate (18/20, 90%) was noted in patients without UGT1A*60 compared to those with UGT1A1*60 (11/22, 50%; p = 0.008). The absence of UGT1A1*60 was also associated with marginally improved progression-free survival (10.3 mo v 7.7 mo, p = 0.081) and overall survival (26.8 mo v 15.1 mo, p= 0.044) compared to the presence of the variant allele. Conclusions: UGT1A1*6 and a haplotype containing UGT1A6*2 and UGT1A7*3 may be associated with irinotecan-related gastrointestinal toxicities. Phenotypic association of UGT1A1*60 and efficacy of the three-drug regimen requires further investigation.
Prenatal exposure to influenza and the development of schizophrenia: is the effect confined to females?
Authors: N Takei, P Sham, E O'Callaghan, G K Murray, G Glover, R M Murray
Journal: American Journal of Psychiatry (1994)

The question of whether prenatal exposure to influenza epidemics is associated with an increased risk of later schizophrenia remains controversial. The authors examined this relationship, using data on the dates of birth and gender of 3,827 schizophrenic patients born in England and Wales between 1938 and 1965 and first admitted to hospitals in the 1980s, the numbers of live births between 1938 and 1965, and the numbers of deaths attributed to influenza between 1937 and 1965. The analysis showed that females, but not males, exposed to influenza epidemics 5 months before birth had a significantly greater rate of adult schizophrenia.
Improving survival for metastatic non-small cell lung cancer: A SEER database analysis from 1990 to 2005
Authors: D. Morgensztern, S. N. Waqar, F. Gao, R. Govindan
Journal: Journal of Clinical Oncology (2009)

8078 Background: Treatment of metastatic non-small cell lung cancer (NSCLC) has evolved over the last decade with the increased use of third-generation chemotherapy agents, established benefits from second-line chemotherapy, and the development of targeted agents. We conducted a study to evaluate whether these treatment advances translated into improved survival in a large registry database. Methods: The Surveillance Epidemiology and End Results (SEER) registry was queried for patients with NSCLC stage IV, aged 21 or older, and diagnosed between 1990 and 2005. Overall Survival (OS) rates were estimated by the Kaplan-Meier method and compared using log-rank test. Cox proportional hazard model was fitted to evaluate whether the diagnostic period is an independent predictor for OS. Demographic variables included period of diagnosis (1990–1993 or P1, 1994–1997 or P2, 1998–2001 or P3, and 2002–2005 or P4), age, gender, race, and histology. Results: There were 127,816 patients meeting eligibility criteria. Median age at presentation was 67 and most patients were male (58%), white (81%), and had adenocarcinoma (39%). Although there was no significant differences in OS between periods 1 and 2 (p = 0.18), there was a significant improvement from periods 2 to 3 (p &lt; 0.001) and 3 to 4 (p &lt; 0.001). 1-y and 2-y OS increased from 13.2% and 4.5% respectively in P1 to 19.4% and 7.8% respectively in P4. Predictive factors for improved survival in multivariate analyses included diagnostic period (p &lt; 0.001), younger age (p &lt; 0.0001), female gender (p &lt; 0.0001), and non-black race (p &lt; 0.0001). After adjusting for demographic factors, there were no significant differences in OS between adenocarcinoma and squamous cell from P1 to P3 (1990–2001). However, P4 showed a significant increase in OS for adenocarcinoma compared with squamous cell (p = 0.02). Conclusions: There has been a significant improvement in OS for stage IV NSCLC over the last 8 years. The recent differences in outcomes based on histology observed in P4 may reflect the increased activity of newer therapies in adenocarcinoma compared with squamous cell, including gefitinib and erlotinib. No significant financial relationships to disclose.
Treatment of cancer-related anorexia with olanzapine and megestrol acetate
Authors: R. M. Navari, M. C. Brenner
Journal: Journal of Clinical Oncology (2008)

9576 Background: Cancer-related anorexia (CRA) and weight loss is a major clinical problem in up to seventy percent of patients with advanced disease. The use of megestrol acetate (MA) has resulted in weight gain in some CRA patients, but MA has had less effect on improving appetite and quality of life (QOL). Olanzapine (OLN) has been shown to be a safe and effective antiemetic in patients receiving chemotherapy and has been used successfully to treat chronic nausea and emesis. Methods: Adult patients with advanced gastrointestinal or lung cancer (Stages III-IV) with 5% or more loss of pre-illness stable weight were randomized to receive MA (800 mg/day) or MA (800 mg/day) plus OLN (5 mg/day) for eight weeks. Patients were excluded if they had undergone major surgery, chemotherapy, or radiotherapy in the previous four weeks, had active dysphasia or GI tract obstruction, or were receiving systemic corticosteroids. Patients were assessed weekly using the M.D. Anderson Symptom Inventory (MDASI) with specific measurement of weight, appetite, nausea, and QOL measures. Eighty patients (median age 63, range 39 - 81, 36 females, Eastern Cooperative Oncology Group Performance Status ≤ 2) consented to the protocol and 76 were evaluable. Results: Twenty-one of the 37 patients receiving MA experienced a 5% weight gain over the initial four week period; the weight gain was maintained for an additional four weeks. There was no significant change in appetite, nausea, or QOL measures at four weeks or eight weeks. Thirty-five of the 39 patients receiving MA plus OLN had a significant improvement (p<0.01) in weight, appetite, nausea, and QOL measures at four and eight weeks. There were no Grade III or IV treatment-related toxicities in patients receiving MA or the combination of MA plus OLN. Conclusions: The combination of OLN and MA appears to be an effective intervention for patients with CRA. No significant financial relationships to disclose.
A 10-year retrospective analysis of risk factors, patterns of cancer recurrence, and survival after liver transplant for cirrhosis and hepatocellular carcinoma
Authors: A. O. Kaseb, M. Bansal, I. Wollner, V. Shah, D. Moonka, G. Divine, M. Abouljoud
Journal: Journal of Clinical Oncology (2007)

4617 Introduction: Determining eligible patients who are likely to have better outcomes following orthotopic liver transplant (OLT) for cirrhosis and hepatocellular carcinoma (HCC) is an ongoing challenge. In addition, tumor recurrence represents a major limitation of long-term survival in this setting. Patients and Methods: The study analyzed 72 OLT recipients for cirrhosis and HCC, between 1996–2006. The endpoints were frequency, patterns, localization, and risk factors of recurrence. Survival from time of OLT to recurrence was compared with primary tumor and patient characteristics, and type of treatment received pre- and post-OLT using univariate and multivariate analyses. Survival was estimated using Kaplan-Meier plots. Results: 13 recurrences (18%) occurred after a median of 33.4 months follow up (6–123 months). 11/13 (84.6%) were distant metastases. Using cox regression analysis and log-rank p-value; bilobar involvement, a tumor number of =3, tumor grade 2 or 3, size &gt;3 cm, vascular invasion, and elevated AFP at diagnosis were all positively associated with recurrence (either distant or any). Tumors that met Milan criteria were associated with a lower likelihood of recurrence. In addition, Pre and post-OLT treatments were not found to be associated with significantly improved disease-free survival. Conclusions: Our analyses confirmed that advanced pathologic features are independently associated with significantly shorter disease-free survival. Pre- and post-OLT treatment modalities were not observed to improve disease-free survival for patients with bad prognostic indicators. However, this is limited due to our small sample size and our univariate anaylsis. We conclude that careful patient selection based on prognostic indicators would maximize benefit from use of this expensive and limited resource. [Table: see text] No significant financial relationships to disclose.