tbuckley/cabot-search huggingface dataset:
Exploratory phase II study of celecoxib and infusional fluorouracil as second-line treatment for advanced pancreatic (PDAC) and biliary tree cancer (BTC)
Authors: M. Milella, A. Gelibter, S. Di Cosimo, E. Bria, E. M. Ruggeri, P. Carlini, P. Malaguti, M. Pellicciotta, E. Terzoli, F. Cognetti
Journal: Journal of Clinical Oncology (2004)

4183 Background: Cyclo-oxygenase-2 (COX-2) is upregulated and may play an important pathogenetic role in both PDAC and BTC. The present study was aimed at evaluating the feasibility, toxicity, and preliminary activity of a selective COX-2 inhibitor (celecoxib) combined with infusional 5-FU as second-line treatment for advanced PDAC and BTC pts. Methods: Advanced PDAC and BTC pts with confirmed progressive disease after Gem-based chemotherapy were eligible for this exploratory phase II study. Treatment consisted of oral celecoxib (400 mg b.i.d.) and p.i.v.i. 5-FU (200 mg/m2/d), both given continuously for a maximum of 9 treatment months, in the absence of progression or unacceptable toxicity. Pts were examined weekly for toxicity and restaged every 6 to 8 wks for tumor assessment. Results: 20 pts (median age: 63 yrs, range: 35–80; M/F: 11/9; PDAC/BTC: 17/3; locally advanced/metastatic disease: 3/17; ECOG PS 0/1/2: 6/11/3) entered the study. The median number of treatment wks administered was 4 (range 2–33); all pts and 158 treatment wks were evaluable for toxicity. Asymptomatic transaminase elevation was the most common toxicity and reached grade 3/4 in 5 out of 158 (3.2%) treatment wks. No other hematological or non-hematological toxicity greater than grade 2 was observed. Four pts discontinued celecoxib due to upper gastrointestinal tract toxicity. Two confirmed PR (duration: 23 and 50+ wks, respectively) and 2 SD (duration: 10 and 13 wks, respectively) were observed for an ORR of 10% (95% C.I. 0–23%) in the intent-to-treat population. Significant (≥ 50%) decrease in serum CA19.9 levels was observed in 3 out of 9 evaluable pts. Median time to progression was 8 wks and median overall survival was 14 wks. Conclusions: The combination of celecoxib and p.i.v.i. 5-FU is feasible, well tolerated, and may induce durable objective responses even in far advanced, Gem-resistant/refractory PDAC or BTC pts. Further exploration of COX-2 inhibitor/fluropyrimidine combinations in these diseases is warranted. No significant financial relationships to disclose.
A phase II trial of perioperative concurrent chemoradiotherapy (CCRT) and gefitinib (G) in locally advanced esophagus (E) and gastroesophageal junction (GEJ) cancer
Authors: C. P. Rodriguez, D. J. Adelstein, L. A. Rybicki, T. W. Rice, G. M. Videtic, J. P. Saxton, S. C. Murthy, D. P. Mason, D. I. Ives
Journal: Journal of Clinical Oncology (2008)

4547 Background: Since 1999, Cleveland Clinic protocols for locally advanced E or GEJ cancer have used peri-operative CCRT. Despite high locoregional control (LRC) rates, distant metastatic control (DMC) and overall survival (OS) are suboptimal. This phase II study added G to our CCRT regimen in an effort to improve these outcomes. Methods: Eligibility required a diagnosis of E or GEJ squamous cell or adenocarcinoma (ACA), with an esophageal ultrasound stage of at least T3, N1, or M1a. Four-day (d) continuous IV infusions of cisplatin (20mg/m2/d), and fluorouracil (1,000 mg/m2/d) began on d1 of pre-operative radiation (30Gy at 1.5Gy bid). Surgery followed in 4–6 weeks (wks), followed by identical CCRT given 6–10 wks postoperatively. G (250 mg/d) was also started on d1 and given for 4 wks. It was restarted with the postoperative CCRT and given for 2 years. Targeted accrual was 80 patients (pts) with primary endpoints of OS and DMC. Results were retrospectively compared to 93 pts treated with an identical regimen without G. Results: Between 4/03 and 7/06, 80 pts were enrolled. Pt and tumor characteristics were similar to the non-G cohort. Median age was 58 (range 33–75) years; 73 pts (91%) were male and 75 (94%) Caucasian. Tumor began in distal E in 28 pts (35%) and GEJ in 46 (57%), and was an ACA in 75 (94%). Clinical staging was T3N0 in 15 pts (19%), T2–3N1 in 41 (51%) and T4 or M1a in 24 (30%). Induction toxicity was similar in G v. non-G pts except for grade 3–4 esophagitis in 3% v. 14% (p=0.007), neutropenia <1,000/mm3 in 14% v. 38% (p<0.001), and neutropenic fever in 5% v. 17% (p=0.012) respectively. G-specific toxicity included grade >1 rash in 42 pts (53%), and grade >1 diarrhea in 44 (55%). Resection was accomplished in 73 pts (91%) and post-operative CCRT completed in 60 (75%). With a median follow up of 33 (range 11–54) months, 3-year Kaplan-Meier estimates (G v. non-G pts) include: OS (40% v. 28%, p=0.07), DMC (46% v. 33%, P=0.20), and LRC (82% v. 77%, p=0.28). Only 50% of pts are projected to complete 2 years of maintenance G. Conclusions: Although toxicity was not increased by adding G to peri-operative CCRT, maintenance G was difficult. The suggestion of a survival advantage in this retrospective comparison merits additional investigation. No significant financial relationships to disclose.
Suicide gene therapy using adenovirus encoded nitroreductase and CB1954 in patients with locally relapsed prostate cancer
Authors: P. Patel, V. Mautner, P. F. Searle, J. G. Young, D. Hull, J. Ellis, D. M. A. Wallace, H. Y. Leung, L. S. Young, N. D. James
Journal: Journal of Clinical Oncology (2005)

3091 Background: Bacterial nitroreductase (ntr) converts the weak monofunctional alkylating agent CB1954 into a highly cytotoxic bifunctional alkylating agent effective in replicating and quiescent cells. We have previously reported phase I safety and biodistribution studies using intraprostatic injection of a replication defective adenovirus encoding ntr (CTL102). Immunohistochemistry of resected prostate demonstrated dose-related ntr staining in tumour, glandular epithelium and stroma. Increasing the injection volume achieved more widespread ntr expression. We now report a phase I clinical trial in prostate cancer using direct intraprostatic injection of CTL102 + intravenous prodrug CB1954. Methods: Patients with biopsy-confirmed local disease and rising PSA underwent 4 TRUS-guided intraprostatic injection of CTL102 in escalating total doses, from 5x1010 to 1x1012 particles with iv CB1954 24mg/m2 48 hours post injection. Primary endpoints were safety and tolerability; secondary endpoints were efficacy by PSA & biopsy. Results: 11 patients with biopsy-confirmed locally relapsed PCa have been treated with virus and prodrug combination (virus particle dose 5x1010 n=3, 1011n=3, 5x1011 n=3, 1012n=2). Both virus and prodrug injections were well tolerated with no significant toxicity apart from a transient transaminitis at day 8 in 7 patients and mild lymphopenia at day 1 in 9 patients. 10 patients had flu-like symptoms at week one. At month 3, 3/8 patients had stable disease and a further 2/8 patients had a PSA reduction of >10% without any additional treatment from baseline. Mean time to PSA progression (>10% rise in PSA from baseline) was 20.6 weeks (95%CI 13.4, 27.8). Two-thirds of patients remain PSA progression free at 6 months. Conclusions: Direct intraprostatic injection of CTL102 followed by iv CB1954 is feasible and safe. Dose limiting toxicity has not been observed; although efficacy has been a secondary endpoint, there are some encouraging initial results and a further study is underway. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration ML Laboratories PLC ML Laboratories PLC ML Laboratories PLC
Novel proteomics approach for functional identification of regulators of cancer drug response and apoptosis in ex vivo tissue cultures of human colorectal cancer
Authors: M. M. Borner, F. Pirnia Borner, D. C. Betticher, B. Gloor
Journal: Journal of Clinical Oncology (2005)

9658 Background: It is notoriously difficult to study the molecular effects of anticancer drug treatment in vivo. So far, this has been only possible by performing serial biopsies in tumor patients undergoing treatment. An approach to address this problem is to perform ex vivo tissue cultures, where patient tumor tissue is obtained at the occasion of a routine operation and then processed in vitro. The molecular program of apoptosis and the activation status of various signal transduction pathways has been identified as a major determinant of chemotherapy responsiveness in cancer. Methods: To analyze genetic pathways potentially involved in anticancer drug response, we have treated tumor samples from colorectal cancer patients ex vivo with antitumor agents with various mechanisms of action. Cytotoxicity was quantified using a colorimetric dye assay. Proteome profiles of the untreated/treated and normal/cancerous patient samples have been generated by reverse-phase protein microarrays, which are a novel approach to analyze signaling pathways using small numbers of cells microdissected from biopsy specimens. For the feasibility phase of the project, we looked at well established growth factor activation pathways such as p-ERK, p-SAPK/JNK, p-AKT, p-p38, p-JNK, p-IkBa, p-STAT3, proliferation regulatory pathways such as p-histone H3, p-Rb, p-p53, cyclin D1, and pathways involved in apoptosis regulation such as cleaved caspase 3, cleaved PARP, and Bcl-2. Results: We found higher cytotoxic activity of most anticancer agents in cancer tissue as compared to normal tissue of the same organ (colon or liver). There was a prominent down-regulation of p-SAPK/JNK and a less pronounced down-regulation of p-ERK and p-p38 with chemotherapy in tumor samples but not in normal tissue samples. Conclusions: This culture technique allows to treat human tissue with various agents ex vivo to simulate the in vivo treatment situation and to assess cytotoxicity by a simple colorimetric dye assay. With the reverse-phase protein microarray technology activated signalling transduction pathways can be identified on low quantity tissue samples. No significant financial relationships to disclose.
Increased neutrophil actin production and translocation of myeloperoxidase in patients with acetaminophen-induced acute liver failure may contribute to multiorgan failure
Authors: Godhev K. Manakkat Vijay, Gema Vizcay-Barrena, Thomas Tranah, Leanne Glover, Vishal C. Patel, Christine Bernsmeier, Jennifer M. Ryan, Laura J. Blackmore, Xiaohong Huang, Victoria T. Kronsten, William Bernal, Nicholas J. Taylor, Georg Auzinger, Christopher Willars, Julia Wendon, Yun Ma, Barbara Bain, Alice Warley, Debbie Shawcross
Journal: Hepatology (2014)
Prevalence of depression, sleep-related disturbances, and anxiety and their effect on quality of life in patients with adenocarcinoma of the pancreas
Authors: D. Brown, A. Boyd, C. Henrickson, J. Hampton, F. Almani, E. Ben-Josef, M. Zalupski, D. Simeone, J. Taylor, R. Armitage, M. Riba
Journal: Journal of Clinical Oncology (2009)

e15678 Purpose: To evaluate the prevalence of depression, sleep related disturbances and anxiety and their effect on quality of life in patients with recently diagnosed adenocarcinoma of the pancreas who present to a multidisciplinary pancreatic cancer clinic. Methods: Cross-sectional and longitudinal psychosocial distress was assessed utilizing Personal Health Questionnaire 9 (PHQ9) to screen for depression and monitor symptoms during the course of care, the Penn State Worry Questionnaire (PSWQ) for generalized anxiety, and the Sleep Problems Questionnaire 4 (SPQ4)/ University of Michigan Sleep Questionnaire to monitor sleep symptoms. Patients were evaluated at their intake consultation and at subsequent follow up visits. Results: 24 patients (pts; mean age 66 years, 48% females) consented to participate during the 6 month pilot study with longitudinal follow up for 13. The PHQ9 scores on presentation revealed mild to moderate depressive symptoms in 54% (13 pts) of pts and moderately severe depressive symptoms in only 8% (2 pts). A minority (2 pts, 8%) had PSWQ scores characteristic of an anxiety disorder, while 33% (8 pts) had moderate anxiety scores. Only 3 pts (12.5%) scores revealed a clear sleep problem; 10 pts, (41.67%) had no sleep problem and 10 pts had a potential sleep problem. Due to the limited follow up, a statistical difference in scores over time was not observed. Conclusions: Our results indicate that mild to moderate depressive symptoms, anxiety and potential sleep problems are common in patients referred to a multidisciplinary pancreatic cancer clinic. Moderately severe depressive symptoms, severe anxiety and clear sleep problems are not as prevalent as is generally believed. To better characterize the relationship of depression (and potential causes) with pancreatic cancer, additional prospective longitudinal studies are needed. No significant financial relationships to disclose.
Life-threatening dermatologic toxicities to cancer drug therapy: An assessment of the published peer-reviewed literature
Authors: J. Sorrell, D. P. West, C. L. Bennett, D. W. Raisch, M. E. Lacouture
Journal: Journal of Clinical Oncology (2009)

e20592 Background: Stevens-Johnson syndrome (SJS) and Toxic Epidermal Necrolysis (TEN) lie on opposite ends of a clinical spectrum characterized by skin detachment, mucosal involvement and bullous skin lesions. Currently, reporting is in the range of 1–7 cases of SJS and 0.4–1.2 of TEN/million persons/year, with mortality as high as 35%. The association of cancer drug therapy with SJS/TEN has been uncommonly addressed. Methods: We searched Ovid (incl.1950 through Nov 2008), PubMed (incl.1948 to present) and Litt's Drug Eruption Reference Manual (incl.1980 through Oct 2007) using search terms and combination of terms relevant for SJS/TEN and cancer drug therapy. Only primary case reports were included. Histology reporting was not required for inclusion. Results: Of 448 results, there were 20 reports of SJS associated with 12 FDA-approved drugs and 22 reports of TEN associated with 16 FDA-approved drugs. In addition, all cases (cancer therapy and non-cancer therapy) were obtained from Medwatch (through Mar 2008). ( Table ) Conclusions: Whereas mild-moderate dermatologic toxicities including alopecia, nail abnormalities or rashes are frequent with cancer drug therapies, it is essential for the oncologist to be familiar with life-threatening dermatologic toxicities such as SJS and TEN, and the agents that have been associated with such reactions. [Table: see text] [Table: see text]
Safety of ABT-450/r/Ombitasvir plus Dasabuvir With or Without Ribavirin in HCV Genotype 1-infected Patients >= 65 Years of Age: Results From Phase 2 and 3 Trials
Authors: Steven L. Flamm, Edward J. Gane, Jean-Francois J. DuFour, Vinod Rustgi, Vincent G. Bain, Darrell H. Crawford, Pietro Andreone, Tarek Hassanein, Wlodzimierz W. Mazur, Sandra S. Lovell, Barbara Da Silva-Tillmann, Nancy Shulman, Massimo Puoti, Terry D. Box, Ira M. Jacobson
Journal: Hepatology (2014)
Cellular atypia and lung cancer
Authors: Carla Antόnio, Filomena Luís, Silvia Correia, Nuno Sousa, Luís Ferreira
Journal: European Respiratory Journal (2011)

Introduction:  The diagnosis of lung cancer based on imaging and the cytology of sputum, have shown insufficient as for the supervened one. The objective of the work is to describe the clinical profile of patients with atypia the cytology of bronchial aspirated.   Methodology:  Two groups of patients according to the presence or not of atypia in bronchial lavage. It was proceeded the mating intergroups by sex and age. Variables: smoking, comorbidity, alterations imagiologic, bacteriology, endoscopic findings and indication for the fiber optic bronchoscopy (BFC).   Results:  Each group with 108 patients, media age of 71.6±4.2 years, being 86 males and 22 women. In the group with atypia 61.1% of patients were smokers or ex-smokers, 38.9% in the group without atypia. In the group with atypia 48.1% had Chronic Obstructive Pulmonary Disorder (COPD) and in the group without atypia 28.7%. The neoplasia in another body was present in 29.6%, in the group with atypia and 13.9% in the group without atypia. The test of χ2 showed dependence between atypia and smoking and these comorbilidades. In situations of atypia 38 patients were new cytology, 13.2% maintained atypia, without evidence of disease neoplastic/infectious.   Conclusions:  The atypia is associated with smoking, COPD and presence of neoplasia in another body, which are risk factors for lung cancer. The persistence of atypia isolated in bronchial lavage with computed tomography, in the BFC of white light normal, may justify the use of BFC of autoflurescence and ecobronchoscopy (EBUS), effective techniques for detection of lesions pre-neoplastic. Prospective studies will be necessary to determine the conduct proper, in situations of persistence of atypia without identification of lesion.
Primary mediastinal large B-Cell lymphoma: A condition with poor prognosis. A case series study from Iranian National Research Institute of TB &amp; Lung Disease
Authors: K. Khodadad, A. Azadi, A. H. Abdollah Shamshirsaz, S. Karimi
Journal: Journal of Clinical Oncology (2005)

6733 Background: Primary mediastinal large B-cell lymphoma (PMLBL) is thought by some to be a distinct disease entity with bulky mediastinal mass and low-stage disease. There is a female predominance and a median age of diagnosis in the fourth decade. Based on the majority reports from western countries; this type of lymphoma has dramatic response to combination chemotherapy and mediastinal radiotherapy, although controversy exists regarding the response to therapy and prognosis. The purpose of this study is to evaluate the efficacy of a combined modality treatment, and determining the objective overall survival and disease-free survival in the patients with PMLBL. Methods: Between 2000 and 2004, 17 patients with PMLBL have been admitted in our center. Fifteen of these patients underwent one of two standard chemotherapy regimens (CHOP, 8 cycles or MACOP-B) combining with mediastinal radiotherapy. Retrospectively, we evaluated the response rate, disease free survival and overall survival. Two patients were not accessible for treatment evaluation. Results: In the 17 patients with PMLBL, male to female ratio was 10:7 and a median age of 31 years. Stage I/II disease was present in 82.8% of patients without any bone marrow involvement. Among 15 treated patients complete response, partial response, stable disease and progressive disease were 73.3% (11/15), 6.6% (1/15), 13.2% (2/15) and 6.6% (1/15), respectively. Five patients (5/12, 41.6%) in responder group were relapsed. Median overall survival was 26 months. One-year and 2-year overall survival were 58.7% and 17.6%, respectively. Failure-free survival was 19.2 months. Conclusions: Although a very limited patients have been evaluated in our study but it seems that the prognosis is so grave in our group compare to western reports. It is interesting that in our study there was male predominance. We speculate that the nature of PMLBL is different from western type of this disease. Based on our experience this kind of lymphoma in our country demands more aggressive approach and the patients may benefit autologous stem cell transplantation after achieving complete remission. No significant financial relationships to disclose.
Pegylated liposomal doxorubicin (PLA) at a metronomic schedule for patients with advanced breast cancer (ABC)
Authors: F. Nolè, E. Verri, G. Sanna, E. Munzone, C. Catania, G. Ascione, L. Adamoli, S. Dellapasqua, M. Colleoni, A. Goldhirsch
Journal: Journal of Clinical Oncology (2006)

10571 Background: The anti-angiogenic efficacy of chemotherapy (CT) is probably best obtained by administration of low doses of cytotoxics on a frequent or continuous schedule. The aim of this pilot study was to assess feasibility, clinical efficacy and tolerability of PLA, using a “metronomic” schedule in ABC. This schedule has been previously tested in the treatment of Kaposi sarcoma. Methods: From January to November 2005, 36 pts with ABC were treated with PLA, at a dose 20 mg/m 2 q14. Almost all the pts were heavily pretreated for ABC and 44% of them received previous anthracycline therapy in adjuvant or metastatic setting. Results: Thirty-four pts were evaluable for toxicity and 29 for response. One pt (3%) had CR, 3 (11%) PR, 12 (41%) NC and 13 (45%) PD, for an overall clinical benefit of 28%. Median response duration was 2.59 mos; median TTP was 3.38 mos (95% CI 2.11–4.64). Treatment was well tolerated with neither G3-G4 NCI-CTC hematological toxicity. Only one pt experienced G3 palmar-plantar erythrodysesthesia (PPE). PPE was observed in other 15 pts (39%), with G2 occurring in 7 (21%). Other common G2 non-hematological toxicities were mucositis in 3 pts (9%) and constipation in 3 pts (9%) Dose reduction, due to subjective or hematological toxicity, was required in 10 pts (36%). No decrease in LVEF &gt; 10% from baseline was observed. Conclusions: Metronomic PLA schedule in pretreated ABC pts seems to be an active and well-tolerated regimen. As to dose-dense CT, targets of metronomic CT might be, in addition to malignant cells, also endothelial and other stromal cells of the progressing metastasis, leading ultimately to the stability and eventually regression of the neoplastic lesion. The lower toxicity profile of the metronomic schedules make their use in pts with ABC very attractive and their testing in the adjuvant setting extremely challenging. No significant financial relationships to disclose.
Estimating the real cost of adjuvant (A) trastuxumab (T) in patients(pts) with HER-2+ (H+) early stage breast cancer (ESBC)
Authors: E. Wilson, J. Crown, J. Ballot, D. McDonnell, E. Sheehan, J. Healy
Journal: Journal of Clinical Oncology (2006)

6081 Background: Pts with H+ metastatic (M) ESBC have a high risk of relapse. T has been reported to reduce the risk of relapse for pts with H+ESBC by approximately 50% when combined with A chemotherapy (CT). We attempted to study the real cost of AT in the context of current use of T in MBC (MT), and of the predicted reduction in the risk of relapse. Methods: We conducted a retrospective analysis of the mean per pt cost of AT and MT, and standard ACT in St. Vincent’s Hospital. The costs/pt for AT and MT were €34k, and €47k respectively, and for the listed agents in standard A: docetaxel(D)-8.8k, paclitaxel(P)-7.4 k, filgrastim(G)-9.3 k. Based on published/presented data (BCIRG 001), we assumed a 35% risk for relapse at five years for pts with H+BC receiving conventional A, and a 50% risk reduction (RR) for AT, giving an absolute benefit of 17.5%. We then devised an equation to calculate the C rp for AT: C rp =[a-M(NR A /10 4 )]/[NR A /10 4 ] where a = cost per pt for treatment (Tx) with AT, M = cost per pt for Tx with T in MBC, N = % of pts relapsing after standard A, R A = % reduction in the risk of relapse after Tx with AT (over standard A). Results: The corresponding real T costs/100 pts for the following reductions in relapse rate would be:25%-€3.4m 50%-€2.6m-, 80%-€2.1m, 100%-€1.8m. The C rp for AT with a 50% reduction in relapse rate is €147k. With a 100% reduction in the RR we estimate the C rp to be €50k. We studied D (D-BCIRG 001), P (P-CALGB 9344) and G (G-CALGB 9741 dose-dense), and noted the following published absolute relapse reductions for these tx: D-7%, P-5% and G-4%. The following costs per relapse prevented were calculated: P-148 k; G-231k; D-126k. Conclusions: Using the equation, the real cost per relapse prevented of AT can be calculated, and comparisons made with the cost-effectiveness of other accepted A. Assuming no re-treatment with MT, AT appears to be a relatively cost-efficient means of reducing relapses. Reports of the efficacy of short AT regimens suggest the possibility of even greater cost-effectiveness. This equation could possibly be used to calculate the cost effectiveness of other novel A molecular therapies. [Table: see text]