tbuckley/cabot-search huggingface dataset:
A randomized placebo-controlled phase III study of docetaxel/carboplatin with celecoxib in patients (pts) with advanced non-small cell lung cancer (NSCLC): The NVALT-4 study
Authors: H. Groen, M. M. Hochstenbag, J. W. van Putten, A. Vincent, O. Dalesio, B. Biesma, H. J. Smit, A. Termeer, B. E. van den Borne, F. M. Schramel
Journal: Journal of Clinical Oncology (2009)

8005 Background: Cox-2 is overexpressed in NSCLC tumors and has a negative impact on survival. It is involved in proliferation and angiogenesis. The hypothesis is that celecoxib by inhibiting Cox-2 enzyme will prolong survival and may increase response to chemotherapy. Methods: We performed a phase III study with planned sample size of 540 pts. Included were pts with pathologically proven NSCLC, no prior chemotherapy, PS=0–2, measurable disease, adequate organ functions. Excluded were pts with CHF NYHA class II-IV, atherosclerotic diseases, gastrointestinal bleeding, symptomatic brain metastases and chronic use of NSAIDs (defined as 1 wk for &gt;3 wks per yr or more than 21 days throughout the year). Acetylsalicylic acid (ASA) ≤ 150 mg/d was allowed. Pts were treated with docetaxel 75 mg/m 2 ;, carboplatin (AUC = 6 mg/ml.min) every 3 wks for 5 cycles and randomized for celecoxib (cel) 400 mg bd, starting on day 1 for 3 years or placebo (plac) 400 mg bd. Stratification was by WHO PS (0–1 vs. 2), stage (IIIB vs. IV), ASA (yes vs. no) and hospital. Primary endpoint was overall survival. Results: From July 2003 until Dec 2007 561 pts were randomized (cel 281 pts, plac 280 pts). Median follow-up was 36 months (mo). Median (range) age 61 yrs(33–84), M/F 63/37%, PS 0/1/2 45/48/6%, adeno/large cell/squamous/other 48/27/18/7%, stage IIIB/IV 17/83%, 11% of pts used acid ≤ 150 mg/day. Reason to end treatment (cel/plac arm) was therapy completed (51/45%), PD (17/22%), adverse events (8/10%), death (8/8%). Toxicity was mild and no increase in cardiovascular events were observed in cel arm. CR, PR, SD, PD in cel/plac arm was 0/1%, 33/26%, 35/40%, 14/19%, respectively. Response rate in evaluable pts was better in the cel arm (p=0.05). Median PFS (95% CI) was 5,5 mo ( 4,3 - 6,8), OS was 8,3 mo (7,5 - 8,8), not different for both arms. HR stratified by ASA and PS for PFS and OS was 0,94 (0.79–1.13) and 0.95 (0.79–1.15), respectively. Conclusions: Addition of celecoxib to first line chemotherapy improves response rate but not progression-free interval or overall survival. No significant financial relationships to disclose.
Localized but unresectable neuroblastoma: treatment and outcome of 145 cases. Italian Cooperative Group for Neuroblastoma.
Authors: A Garaventa, B De Bernardi, C Pianca, A Donfrancesco, L Cordero di Montezemolo, M T Di Tullio, S Bagnulo, A Mancini, M Carli, A Pession, A Arrighini, A Di Cataldo, P Tamaro, V Iasonni, A Taccone, D Rogers, L Boni
Journal: Journal of Clinical Oncology (1993)

PURPOSE To define factors that influence outcome in children with localized but unresectable neuroblastoma by retrospective investigation of response to therapy and outcome in 21 Italian institutions. PATIENTS AND METHODS Of 145 assessable children diagnosed between 1979 and 1990, 77 were treated between 1979 and 1984 with three consecutive standard-dose (SD) protocols, and 68 between 1985 and 1990 with a high-dose (HD) protocol. All protocols included chemotherapy, followed by resection of primary tumor if feasible. If at least partial resection was achieved, consolidation therapy followed, except that from 1985 onward, patients considered disease-free following surgery received no further treatment. RESULTS Ninety-four of 145 patients (65%) achieved a complete response (CR) or partial response (PR) with chemotherapy and 75 (52%) subsequently underwent complete resection of the primary tumor. Eighty-one patients are alive (73 without disease, eight with disease), 63 have died, and one is lost to follow-up. The 5-year overall survival (OS) rate is 55% and progression-free survival (PFS) rate 50%. Both OS and PFS correlated with response to chemotherapy, removal of primary tumor, HD therapy, and serum lactate dehydrogenase (LDH) levels. Infants (&lt; 1 year), independent of primary tumor site, and children aged 1 to 15 years with a nonabdominal primary tumor, did better compared with children aged 1 to 15 years with an abdominal primary tumor (PFS, 72% and 64% v 30%; P &lt; .001 and &lt; .01, respectively). Outcome of this last group improved with the HD protocol (PFS, 40% v 23%; P = .01). CONCLUSION In children with unresectable neuroblastoma, risk categories can be defined by age and primary tumor site. HD chemotherapy should be investigated for the poor-risk category age 1 to 15 years with an abdominal primary tumor.
Physical Activity and Survival After Prostate Cancer
Authors: Christine M. Friedenreich, Qinggang Wang, Heather K. Neilson, Karen A. Kopciuk, S. Elizabeth McGregor, Kerry S. Courneya
Journal: European Urology (2016)

Despite the high global prevalence of prostate cancer (PCa), few epidemiologic studies have assessed physical activity in relation to PCa survival. To evaluate different types, intensities, and timing of physical activity relative to PCa survival. A prospective study was conducted in Alberta, Canada, in a cohort of 830 stage II–IV incident PCa cases diagnosed between 1997 and 2000 with follow-up to 2014 (up to 17 yr). Prediagnosis lifetime activity was self-reported at diagnosis. Postdiagnosis activity was self-reported up to three times during follow-up. Cox proportional hazards models related physical activity to all-cause and PCa-specific deaths and to first recurrence/progression of PCa. A total of 458 deaths, 170 PCa-specific deaths, and, after first follow-up, 239 first recurrences/progressions occurred. Postdiagnosis total activity (>119 vs ≤42 metabolic equivalent [MET]-hours/week per year) was associated with a significantly lower all-cause mortality risk (hazard ratio [HR]: 0.58; 95% confidence interval [CI], 0.42–0.79; p value for trend <0.01). Postdiagnosis recreational activity (>26 vs ≤4 MET-hours/week per year) was associated with a significantly lower PCa-specific mortality risk (HR: 0.56; 95% CI, 0.35–0.90; p value for trend = 0.01). Sustained recreational activity before and after diagnosis (>18–20 vs <7–8 MET-hours/week per year) was associated with a lower risk of all-cause mortality (HR: 0.66; 95% CI, 0.49–0.88). Limitations included generalisability to healthier cases and an observational study design. These findings support emerging recommendations to increase physical activity after the diagnosis of PCa and would inform a future exercise intervention trial examining PCa outcomes. In a 17-yr prostate cancer (PCa) survival study, men who survived at least 2 yr who were more physically active postdiagnosis or performed more recreational physical activity before and after diagnosis survived longer. Recreational physical activity after diagnosis was associated with a lower risk of PCa death.
Phase II study of bortezomib for castrate metastatic prostate cancer (PC)
Authors: M. J. Morris, K. W. Beekman, W. K. Kelly, S. F. Slovin, D. Shaffer, C. Eicher, E. Chu, T. Curley, A. Delacruz, H. I. Scher
Journal: Journal of Clinical Oncology (2005)

4633 Background: Bortezomib (VELCADE, Millennium Pharmaceuticals, Cambridge, MA) is a proteasome inhibitor that induced PSA declines in patients (pts) with castrate metastatic PC in phase I studies. PSA declines appeared to correlate with declines in IL-6 levels. In vitro, steroids synergize with bortezomib. We performed a phase II study to determine the efficacy of bortezomib and prednisone (pred), and to clarify the relationship between PSA and IL-6. Methods: Two groups of pts with progressive castrate metastatic PC were treated. Pts in Group 1 had no limitations on prior steroids and chemo, and received induction with bortezomib using 1.5 mg/m2 IV twice weekly on weeks 1, 2, 4, and 5. Starting week 7, pts received 1.6 mg/m2 weekly, 4 out of every 6 weeks, as maintenance. Pred 10 mg PO was given throughout. Group 2 was restricted to pts with ≤1 prior chemo regimen and ≤6 months of prior steroid use. They received 1.3 mg/m2 induction and 1.6 mg/m2 maintenance per the above schedule. Pred was added if the PSA rose by ≥25% after 6 weeks of bortezomib alone. PSA and IL-6 were assessed at weeks 1, 4, 7, 13, and 19; scans were obtained every 12 weeks. Results: 18 pts were in Group 1; 13 were evaluable for response. 12 pts received prior chemo and 17 received prior steroids. 12 pts were in Group 2; 9 were evaluable for response, 4 of whom crossed over to receive pred. None received prior chemo and 3 received prior steroids. No >50% PSA declines were seen in either cohort. Overall, 2 pts had stable disease as best response at 12 weeks, while all others progressed. No grade 4 toxicities were felt to be attributable to drug. Grade 3 toxicities felt possibly to be drug-related included anemia (13%), leukopenia (30%), neuropathy (3%), thrombocytopenia (20%), and syncope (3%). No significant differences in toxicity were seen between groups. The median baseline IL-6 level was 4.55 pg/ml (range <3.12–107.1, ULN 8). Baseline IL-6 was above ULN in 27% of pts. IL-6 declined from baseline in 43% of pts (median 62%, range 10–100%). Conclusions: No significant antitumor activity has been seen in this study using bortezomib alone or with pred for castrate metastatic PC. IL-6 declines have not correlated with changes in PSA. Accrual will be completed shortly. Support: MPI, CA102544, Prostate Ca Foundation Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Millennium
Phase I and pharmacokinetic study of Kahalalide F in patients with advanced androgen refractory prostate cancer
Authors: J. H. Beijnen, J. M. Rademaker-Lakhai, S. Horenblas, W. Meinhardt, E. Stokvis, T. M. De Rijke, J. M. Jimeno, L. Lopez Lazaro, J. A. Lopez Martin, J. Schellens
Journal: Journal of Clinical Oncology (2004)

2076 Introduction: Kahalalide F (KF) is one of a family of novel dehydroaminobutyric acid-containing peptides isolated from the Hawaiian herbivorous marine species of mollusk, Elysia rufescens, with preclinical selective activity against androgen independent prostate tumors. The objectives of this study were to identify the maximum tolerated dose, to explore the toxicities, pharmacokinetics (PK) and anti-tumor activity of KF. Methods: KF is administered as a one-hour i.v. infusion, daily*5 every three weeks in patients with advanced or metastatic androgen refractory prostate cancer with progressive disease prior to entry. The starting dose was 20 μg/m2/day. Bioanalysis of KF was performed during the first and second course by LC-MS/MS. PSA levels of each patient were also evaluated to determine activity of KF. Results: 33 patients were registered with a median age of 68 years (range 49–81) and median WHO PS 1 (range 0–2). One patient per level was entered at 20, 40, 80 and 160 μg/m2/day. Due to reversible CTC grade 3 transaminase elevation, 5 patients were entered at 320 μg/m2/day. Three patients were entered at 425 μg/m2/day, 7 patients were included at 560 μg/m2/day, 11 patients were entered at 700 μg/m2/day and 3 patients were included at dose level 930 μg/m2/day. Drug related toxicities were rapidly reversible CTC grade 3 and 4 AST and ALT that occurred at 560, 700 and 930 μg/m2/day and phlebitis and hypersensitivity reactions. PK suggested a linear dose-AUC relationship up to the dose of 560 μg/m2/day. Thereafter a more than proportional increase was observed. Total plasma clearance was 11.02 L/h (±4.54) and terminal half-life 0.54 h (±0.14). One patient had a PSA partial response following protocol criteria. There were 3 patients with SD, lasting in one of them for 7 months and for 3 months in the other 2. Conclusion: At this schedule the maximum tolerated dose of KF was 560 μg/m2/day. No significant financial relationships to disclose.
The Limits to Setting Limits on Critical-Care Delivery: Response to Open Peer Commentaries on “Balancing Legitimate Critical-Care Interests: Setting Defensible Care Limits Through Policy Development”
Authors: Jeffrey Kirby
Journal: The American Journal of Bioethics (2016)

It was a pleasure to read, and engage with, the six submitted, open peer commentaries on my target article (Kirby 2016). I am grateful to the authors for sharing their varied, insightful perspectiv...
Analysis according to prognostic factors in patients (pts) treated with first-line bevacizumab (BEV) combined with paclitaxel (PAC) for HER2-negative metastatic breast cancer (mBC) in a routine oncology practice study.
Authors: Iris Schrader, Frank Gerhard Foerster, Andreas Schneeweiss, Matthias Geberth, Lars Hahn, Claudia Schumacher, Martin Michael Hertz-Eichenrode, Winfried Schoenegg, Matthias Kim Wolfgarten, Andreas Kutscheidt, Marcus Schmidt, Bahriye Aktas
Journal: Journal of Clinical Oncology (2012)

1077 Background: 1st-line BEV combined with weekly PAC significantly improves progression-free survival (PFS) and response rate (RR) vs PAC alone in HER2-negative mBC, as shown in E2100. We analyzed data from a German routine oncology practice study of 1st-line BEV–PAC according to prognostic factors. Methods: Pts who had received no prior chemotherapy for mBC received BEV–PAC according to the European label. Efficacy and safety were documented for up to 1 y (or until progression, death, or BEV discontinuation if earlier) with additional long-term follow-up. Efficacy was analyzed in clinically important subgroups. Results: Efficacy data were available for 818 pts. The median duration of follow-up was 11.4 mo. The composition of the pt population with respect to the subgroups below was generally similar to the population treated in E2100, except for a higher proportion of pts with visceral disease or metastases in &lt;3 organs. RR was very similar across all subgroups analyzed. Differences in median PFS and OS were generally in line with the differing prognoses according to clinical characteristics. Conclusions: These data suggest that 1st-line BEV–PAC is typically associated with median PFS &gt;9 mo in the real-life setting, irrespective of baseline characteristics. [Table: see text]
Morphological pattern of MR mammography in breast cancer patients with HER2 overexpression.
Authors: A. Artmann, N. A. Boehm, I. Laemmer-Skarke, K. Annecke, M. Settles, V. R. Jacobs, M. Kiechle, E. J. Rummeny
Journal: Journal of Clinical Oncology (2010)

e11038 Background: So far there is limited evidence regarding an association between breast MRI features and histopathological prognostic factors. To investigate kinetic and morphologic MR features as useful preoperative predictors in invasive breast cancer for tumor biological activity and c-erbB-2 overexpression an investigation between “triple positive” and “triple negative” patients was initiated. Methods: In a retrospective study n= 80 patients, mean age 52 years (range 31-74), scheduled for surgery for FNB-confirmed invasive ductal breast cancer, with n=41 triple positive (HER2 overexpression c-erbB-2+++, ER +, PR +) and n=39 triple negative as control group underwent 3D (Gd)- enhanced 1.5T MR mammography preoperatively using a T1-w FLASH pulse sequence. Two radiologists assessed the images in consensus reading. MR features included tumor shape, margin, presence of washout phenomenon and especially early (EPRM) and late (LPRM) peripheral rim enhancement. These features were correlated with the immunohistochemically detected biomarkers. Results: The results show that the incidence of EPRE increased for trend of superiority (≤0.02) in triple positive breast cancer patients, higher histological grade (G2, G3) and larger tumor size (2-5cm; T2) compared to triple negative patients. The EPRE rate was reduced in irregular-shaped lesions vs. round/lobulated- shaped. Conclusions: This study confirms that EPRM correlates with histopathological prognostic factors in invasive ductal breast cancer. Presence of early peripheral rim enhancement besides central necrosis/fibrosis can serve as imaging marker on dynamic MR mammography. Further studies have to determine if EPRM can be standardized as a method and used as predictor for imaging detection of triple negative breast cancer. No significant financial relationships to disclose.
Long-term maintenance capecitabine and celecoxib improved clinical outcomes by targeting colorectal cancer micrometastasis
Authors: M. Zhang, S. Curley, C. Ng, B. Kurland, S. Krishnan, M. Rodriguez-Bigas, N. Janjan, B. Feig, S. Hamilton, E. Lin
Journal: Journal of Clinical Oncology (2007)

14513 Background: Role of mainteance therapy after achieving complete response (CR) remain undefined for patients with metasatic colorectal cancer. We studied prognostic and treatment factors including maintenance capecitabine and celecoxib (XCEL) in all 19 unresectable metastatic colorectal cancer patients (pts) who had CR from the prior XCEL study. Methods: Event charts are used to summarize the timeline of the various treatments. Kaplan-Meier survival estimates and univariate log-rank tests were used to evaluate RFS and OS as time from CR. Prognostic and treatment factors included: tumor size, metastasis number (9 solitary disease), site (13 being extrahepatic), stage on diagnosis (stage II versus III/IV), disease free interval prior to stage IV disease, surgery (5 R0, 3 R1–2 resections), lactate dehydrogenase levels, first-line irinotecan chemotherapy, radiation (9 pts ≥ 45 Gy, 3 Pts &lt; 45 Gy), and maintenance XCEL (duration 0–50.3 months). Results: Nine of 19 patients experienced recurrence (median 13 months after CR), and 4 died during the follow-up period (median 31 months after CR). The 2-year RFS for the unresected and R1–2 resected patients was 71% versus 20% for the R0 resected patients (p = 0.07). This paradoxical RFS pattern corresponded to a RFS advantage for maintenance XCEL (p = 0.002), but not any other prognostic or treatment factors. All relapses occurred in situ following discontinuation of XCEL except for the surgical cases. Patients undergoing maintenance XCEL also benefited in OS (p = 0.04). The median OS from XCEL and from onset of metastasis reached 51.9 months (95% CI, 45 months- not reached [NR]) and 73.3 months (95% CI, NR-NR months) respectively. Conclusions: Maintenance XCEL targets colorectal micrometastases and produces a paradoxical RFS and OS advantage among the high-risk unresected/R1–2 resected patients than R0 resected patients. Prospective studies are warranted to validate roles of maintenance XCEL in the treatment of colorectal micrometastases. No significant financial relationships to disclose.
Causes of Death Following PCI Versus CABG in Complex CAD
Authors: Milan Milojevic, Stuart J. Head, Catalina A. Parasca, Patrick W. Serruys, Friedrich W. Mohr, Marie-Claude Morice, Michael J. Mack, Elisabeth Ståhle, Ted E. Feldman, Keith D. Dawkins, Antonio Colombo, A. Pieter Kappetein, David R. Holmes
Journal: Journal of the American College of Cardiology (2016)

There are no data available on specific causes of death from randomized trials that have compared coronary artery bypass grafting (CABG) with percutaneous coronary intervention (PCI). The purpose of this study was to investigate specific causes of death, and its predictors, after revascularization for complex coronary disease in patients. An independent Clinical Events Committee consisting of expert physicians who were blinded to the study treatment subclassified causes of death as cardiovascular (cardiac and vascular), noncardiovascular, or undetermined according to the trial protocol. Cardiac deaths were classified as sudden cardiac, related to myocardial infarction (MI), and other cardiac deaths. In the randomized cohort, there were 97 deaths after CABG and 123 deaths after PCI during a 5-year follow-up. After CABG, 49.4% of deaths were cardiovascular, with the greatest cause being heart failure, arrhythmia, or other causes (24.6%), whereas after PCI, the majority of deaths were cardiovascular (67.5%) and as a result of MI (29.3%). The cumulative incidence rates of all-cause death were not significantly different between CABG and PCI (11.4% vs. 13.9%, respectively; p = 0.10), whereas there were significant differences in terms of cardiovascular (5.8% vs. 9.6%, respectively; p = 0.008) and cardiac death (5.3% vs. 9.0%, respectively; p = 0.003), which were caused primarily by a reduction in MI-related death with CABG compared with PCI (0.4% vs. 4.1%, respectively; p <0.0001). Treatment with PCI versus CABG was an independent predictor of cardiac death (hazard ratio: 1.55; 95% confidence interval: 1.09 to 2.33; p = 0.045). The difference in MI-related death was seen largely in patients with diabetes, 3-vessel disease, or high SYNTAX (TAXUS Drug-Eluting Stent Versus Coronary Artery Bypass Surgery for the Treatment of Narrowed Arteries) trial scores. During a 5-year follow-up, CABG in comparison with PCI was associated with a significantly reduced rate of MI-related death, which was the leading cause of death after PCI. Treatments following PCI should target reducing post-revascularization spontaneous MI. Furthermore, secondary preventive medication remains essential in reducing events post-revascularization. (TAXUS Drug-Eluting Stent Versus Coronary Artery Bypass Surgery for the Treatment of Narrowed Arteries [SYNTAX]; NCT00114972)
Prognostic factors in stage I non-seminomatous germ-cell testicular tumors managed by orchiectomy and surveillance: implications for adjuvant chemotherapy.
Authors: P Hoskin, S Dilly, D Easton, A Horwich, W Hendry, M J Peckham
Journal: Journal of Clinical Oncology (1986)

Between February 1979 and March 1985, 126 patients with clinical stage I non-seminomatous germ-cell testicular tumors were entered into a surveillance study after orchiectomy. Of this group, 36 (28%) have relapsed. The prognostic significance of 13 clinical, histopathologic, and biochemical factors has been analyzed. Vascular invasion and lymphatic invasion (LI) within the primary tumor, histology, and involvement of the epididymis and rete testis were significantly associated with an increased risk of relapse. However, multiple regression analysis showed that only histology and LI were significant, independent prognostic factors. These findings provide the basis for the consideration of adjuvant chemotherapy for patients with apparent clinical stage I testicular non-seminoma who are at high risk of harboring occult metastases.
Phase II study of cisplatin, epirubicin, oral UFT, and leucovorin as first-line chemotherapy for metastatic gastric cancer
Authors: E. Idelevich, N. Karminsky, M. Dinerman, R. Katsenelson, N. Ben Zvi, N. Ben Baruch, S. Man, A. Shani
Journal: Journal of Clinical Oncology (2006)

14049 Background: A phase II study was conducted to assess the efficacy and tolerability of combination therapy with cisplatin, epirubicin, oral UFT and leucovorin in patients (Pts) with metastatic gastric cancer. Methods: Pts with previously untreated metastatic or unresectable measurable gastric adenocarcinoma received cisplatin 60 mg/m 2 and epirubicin 50 mg/m 2 on day (d)1, UFT 300 mg/m 2 was administered in conjunction with oral leucovorin 30 mg/day in divided daily doses d 1–22, followed by a 7-day rest period. Results: Thirty-nine pts were enrolled in this study. Two achieved a complete response and 13 a partial response, giving an overall response rate of 38.5%. Disease stabilization was achieved in further 16 pts (41%). Median time to progression and median survival were 6.4 and 10.7 months respectively. Grade 3/4 neutropenia, anemia, throbocytopenia, occurred in 10%, 5%, and 2% of pts respectively, and febrile neutropenia occurred in 7 pts (one episode each). Grade 3 diarrhea occurred in 5% of the pts. There were no treatment related deaths. Conclusions: Cisplatin, epirubicin, and oral UFT plus leucovorin, a convenient outpatient regimen, has significant activity and tolerable toxicities in pts with metastatic gastric carcinoma. No significant financial relationships to disclose.