tbuckley/cabot-search huggingface dataset:
Amifostine (A) reduces acute mucosal toxicity of accelerated radiotherapy (ART) and Carboplatin (CBP) in locally advanced head and neck cancer (HNSC)
Authors: L. M. Martin, A. Moran, M. D. Damour, G. Piot, P. Oudinot
Journal: Journal of Clinical Oncology (2004)

5566 Background: ART associated with CBP for the treatment of locally advanced HNSC was highly effective (ESTRO 2002), but acute and late toxicities were intense and may have reduced the therapeutic ratio. A phase II trial was undertaken to evaluate the impact of A upon mucositis rate, other acute / late toxicities, response rate, and overall survival Methods: : Since Nov. 2000, 50 pts with histologically-verified stage III - IV carcinoma of head and neck (WHO ≤ 2, adequate biological parameters) have been treated by RT (3D conformal therapy, 1.5 Gy x 2 / d for 2 w then 2 Gy / d for 4 w, A 200 mg/m2 i.v. before each fr of RT) and CBP (100 mg/m2 / w for 6 w) (arm I). The protocol was amended to add A (340 mg/m2) before CBP (arm II). Pts were weekly assessed for acute toxicity (RTOG scales) from the start until 3 m after the end of RT. Pts were followed for 3 y (late toxicity assessed every 3 m). Results: sex ratio 5 / 45. Median age 55 y (39–75). Primary tumor sites: 3 oral cavity, 28 oro- and 19 hypo-pharynx; AJCC staging: 37 IVA, 13 IVB. To date : 46 pts evaluable: In Arm I, the G 3–4 acute epithelitis rate and the duration of G 3–4 acute mucositis tended to be lower than without A. In Arm II, the incidence of G 3–4 acute mucositis was reduced, consequently, the need for feeding tubes was less frequent. The incidence of hospitalization was similar in the 3 groups. G 3–4 toxicities related to A in arm II were: 1 vomiting, 2 asymptomatic hypocalcaemia, 1 asthenia, 2 cutaneous. All pts have completed RT. 2 pts temporarily interrupted RT (2–14 days) in both arms. The overall CR rate is 75%; calculated local control rate at 1 y is 66%; and OS 63% (17 pts at risk). Conclusions: In this study, severe acute mucosal toxicity was reduced by A infusion before RT (200 mg/m2) and before CT (340 mg/m2). This schedule was well tolerated. These results are encouraging and support moving forward with a phase III randomized study. No significant financial relationships to disclose.
A multicenter, randomized phase III maintenance study of thalidomide (arm A) versus observation (arm B) in patients with malignant pleural mesothelioma (MPM) after induction chemotherapy.
Authors: P. Baas, W. Buikhuisen, O. Dalesio, A. Vincent, N. Pavlakis, R. Van Klaveren, F. Schramel, F. Custers, H. Schouwink, S. A. Burgers
Journal: Journal of Clinical Oncology (2011)

7006 Background: Standard chemotherapy treatment does not lead to long-term survival; new treatment approaches are required. MPM is known for its high vessel count and levels of vascular growth factors. Suppression of the neo-vasculature by adding thalidomide in the maintenance setting might lead to improved progression free survival (PFS). We here report the final results of PFS, overall survival (OS) and toxicity. Methods: Patients with pemetrexed (500 mg/m2) and carboplatin (AUC 5) or cisplatin (75mg/m2)(q3) for ≥ 4 courses and no signs of progression were eligible. After obtaining informed consent patients were randomized to receive thalidomide 200 mg/day orally (A) or no treatment (B). CT scanning of the thorax and physical examination was performed every 2 months or earlier. PFS and OS were calculated from start of randomization. A number of 190 events were required to show an improvement of 50% in PFS. Results: From 05/2004 until 12/2009 222 patients from 8 Dutch and 4 Australian centers were included (111 in each arm). Median age: 64 yrs (range 41-82); 86% epithelial type; 215 WHO 0-1 and 6 WHO 2. Toxicity: Data of 216 (108 arm A; 108 arm B) patients showed few grade III-IV toxicities. Low platelet count was observed in 6 patients in arm A and 11 in arm B (p=0.31). Leukopenia in 2 patients in arm A and 3 in arm B. In arm A, 2 patients experienced constipation and 2 neurosensory problems. Cardiovascular events were seen in 2 cases arm A and 3 in arm B, none being considered treatment related. Based on the physician reported outcome there were 207 progressions observed, with median PFS of 16 weeks in arm A compared to 15 weeks in arm B (p=0.83) HR 1.0 CI 0.8-1.4. Median OS was 11 months in arm A and 13 months in arm B (p=0.09) HR 0.78 CI 0.57-1.1. Conclusions: This is the largest maintenance study in patients with MPM reported so far. There is minimal toxicity associated with the use of thalidomide, however there is also no evidence of benefit in PFS or OS.
An open-label phase II trial to assess to efficacy of sunitinib as an antieffusion agent in patients with malignant peritoneal and/or pleural effusions
Authors: X. Trinh, P. van Dam, W. Tjalma, A. Wojtasik, W. Lybaert, M. Rasschaert, A. Rutten, A. Prové, P. Vermeulen, L. Dirix
Journal: Journal of Clinical Oncology (2009)

e14647 Background: Pleural and peritoneal effusions are common in advanced malignant disease and relative resistant to traditional treatments. VEGF-A is considered to be a crucial factor in the biology of accumulation of malignant effusions (ME). Sunitinib is a multi-targeted TKI with a high potency of inhibiting VEGFR2. A treatment that could symptomatically reduce ME would be useful, regardless of its anti-tumoural or anti-angiogenic effect. Methods: Refractory patients with symptomatic ME were enrolled to receive 2x6 weeks of daily 37.5mg sunitinib regardless of their primary histology or site. Outcome was measured by time to re-puncture or by measurement of volume ME by CT-scan every 6 weeks or at the end of treatment. Puncture fluids and blood samples were collected for extensive biomarker analysis (VEGFA&amp;C, VEGFR1–3, b-FGF, PDGFA-B, PDGFRα-β, PlGF1–2) on consecutive samples. Results: At present 6 patients have been enrolled. Patients had ovarian cancer (N=3), breast cancer (N=2) and squamous cervical cancer (N=1) as primary tumours. All patients had been extensively pre-treated with 4 to 8 lines of systemic therapy. Efficacy: Three (3/6) patients showed regression of effusion fluid by consecutive CT-scans. Two (2/6) patients had unchanged volume and one (1/6) patient had an increase of fluid volume. Follow-up: Two (2/6) patients stopped the trial early due to toxicity. Two patients (2/6) died during treatment due to disease progression elsewhere. Two patients (2/6) completed the 2 cycles of 6 weeks treatment. Of which, one had sustained reduction in volume fluid accumulation, while the other one had initial stabilisation after one cycle but eventually had increasing volume of ascites. Conclusions: These findings support the hypothesis that sunitinib could be useful in the management of ME. Although the numbers are low, in a majority of patients (5/6) there was reduction or stabilisation of fluid accumulation. Toxicity led to study withdrawal in a third of our patients. An update of patient numbers as well as results of translational/biomarker analysis will be presented at the meeting. No significant financial relationships to disclose.
Oral uracil-tegafur (UFT) compared to classical cyclophosphamide/methotrexate/5-fluorouracil (CMF) as postoperative chemotherapy in patients with node-negative, high-risk breast cancer (BC): Results of the national surgical adjuvant study for breast cancer
Authors: T. Watanabe, M. Sano, S. Takashima, T. Kitaya, Y. Tokuda, M. Yoshimoto, N. Kono, K. Nakagami, H. Iwata, Y. Ohashi
Journal: Journal of Clinical Oncology (2007)

551 Background: Oral UFT and classical (c-) CMF provide similar response rates in patients (pts) with metastatic BC (CMF: 36.1%, UFT: 39.3%). In a postoperative setting, these regimens showed comparable effectiveness in terms of odds reductions in relapse-free survival (RFS) (CMF: 23.5%, UFT: 21.0%), but data fromrandomized controlled trials (RCT) is not sufficient. Methods: We conducted a RCT to study the efficacy and toxicity of 2-year oral UFT as compared with c-CMF in pts with Stage I - IIIA node-negative, pathologically high-risk BC in a postoperative setting. In the CMF arm, pts received 6 cycles of c-CMF (C: 100 mg po, days 1 to 14, M: 40 mg/m 2 iv, days 1 and 8, F: 500 mg/m 2 iv, days 1 and 8). In the UFT arm, pts received UFT at 300 mg/m 2 /day po for 2 years. Tamoxifen (20 mg/day) was administered for 5 years if ER or PgR was positive or unknown. The primary endpoint was RFS. Overall survival (OS), toxicity, and quality of life were secondary endpoints. The statistical hypothesis was non- inferiority of UFT in terms of RFS (95% CI of HR: &lt;1.30). Results: From October 1996 through March 2001, a total of 733 pts were enrolled of whom 707 pts were analyzed. Patients’ characteristics were well balanced between the two arms. Median follow-up time was 6.1 years. At 5 years the RFS rate was 88.2% in the CMF arm and 87.7% in the UFT arm, and OS rates were 96.0% and 96.1%, respectively. Hazard ratios of the UFT arm to the CMF arm were 1.05 (95% CI: 0.69–1.57) for RFS and 0.88 (95% CI: 0.48–1.63) for OS. The toxicity profile differed between the groups. Major grade 3 or higher adverse events were as follows: leukopenia (CMF: 3.1%, UFT: 0.3%, p=0.006), neutropenia (CMF: 5.5%, UFT: 3.5%, p=0.27), elevation of total bilirubin (CMF: 0.3%, UFT: 5.5%, p=0.00001), elevation of GOT (CMF: 1.4%, UFT: 5.7%, p=0.004), elevation of GPT (CMF: 5.1%, UFT: 8.9%, p=0.08), nausea/vomiting (CMF: 2.8%, UFT: 1.1%, p=0.18) and diarrhea, (CMF: 0.3%, UFT: 2.0%, p=0.04). Conclusions: Our results suggest that UFT is a promising alternative to CMF as postoperative adjuvant chemotherapy in women with node-negative, high-risk breast cancer. No significant financial relationships to disclose.
Predictive value of MGMT in glioblastoma: A multicenter study
Authors: L. Karayan-Tapon, V. Quillien, J. Guilhot, M. Wager, G. Fromont, S. Sailkali, A. Hamlat, D. Loussouarn, M. Campone, C. Gratas-Rabbia-Ré
Journal: Journal of Clinical Oncology (2008)

22065 Background: MGMT status has been shown to be a predictive marker of response to temozolomide (TMZ) in glioblastoma (GBM) but no consensus has been described so far concerning the best way to determine this status. We performed a retrospective study to compare 5 methods to find the one with the best predictive value. Methods: Tumour samples were collected in 3 clinical centers, after patient's approval, from 81 adult patients with newly diagnosed GBM treated with surgery followed by radiation and concomitant TMZ (Stupp treatment). MGMT promoter methylation was studied by conventional nested MS-PCR (MS-PCR), quantitative MS-PCR (QMS-PCR) and pyrosequencing of 5 CpG sites, mRNA expression by QRT-PCR and protein expression by immunohistochemistry. Each technique was standardized and performed in the 3 centers, except pyrosequencing that was centralized. Quantitative variables were dichotomized according to their median values. For immunohistochemistry, samples with less than 10% were considered as negative whereas positive samples were dichotomized. Prognostic factors for overall survival (OS) were tested using the Kaplan-Meier method and log-rank test and then by a Cox regression model. Results: With median follow-up of 15.3 months, patients positive for MGMT methylation (68%) by MS-PCR and those with a percentage of methylation higher than the median values showed an OS time longer than the others (MS-PCR: p=0.014, QMS-PCR: median 35%, p<10−3, pyrosequencing: median 8%, p<10−3 for mean methylation levels, and p<10−2 for each position). The relationship between mRNA expression and survival was weaker (p=0.039), and none was observed for protein expression (median: 15%). Age was also shown as being of prognostic value (p=0.008). In multivariate analysis, 3 variables were considered as adding prognostic information to each other: age (p=0.008), pyrosequencing in position 3 and 4 (p=0.034 and p<10−3 respectively). Conclusions: In our series, all three methods for the determination of MGMT methylation status allowed us to significantly discriminate patients who responded to TMZ, however pyrosequencing seems to be the most powerful tool. In contrast protein expression, although frequently used, was not informative. No significant financial relationships to disclose.
The impact of genetic factors in the development of thrombosis in cancer patients
Authors: M. Özkan, I. Koçyigit, M. Dikilitas, Y. Özkul, I. Sari, H. Karaca, F. Emirogullari, B. Eser, O. Er, A. Unal
Journal: Journal of Clinical Oncology (2009)

e22227 Background: Thromboembolism is frequent in patients with cancer. Although it is known that several acquired factors take place in this process, the role of the genetic factors is controversial. In this study we analysed the most common genetic polymorphisms which have a role in the development of thrombosis. Methods: Study population consists of 292 (158 with thrombosis and 134 without thrombosis) patients treated between 2004 and 2008. Thrombosis was diagnosed by clinically and radiological measures in any time during the course of disease. Factor V Leiden G1691A, Prothrombin G20210A, Methlene Tetra Hydrofolate Reductase (MTHFR) C677T and Plazminogen Activator Inhibitor (PAI-1) 4G/5G were analysed with PCR-RFLP (Polymerase Chain Reaction- Restriction Fragment Length Polymorphism). Results: In the study group 48 and 1 patient had heterozygot and homozygot polymorphism for Factor V Leiden G1691A respectively. In the control group 32 heterozygot and 1 homozygot polymorphism and there was no statistically significant differents between study and control group (p=0,462).For Protrombin G20210A 11 and 4 heterozygot polymorphism were observed in control and study group respectively. While there was 1 homozygot polymorphism in study group there was no in control group and the difference between two groups was not statistically significant (p=0,198). For MTHFR C677T, 48 and 24 heterozygot polymorphism, 15 and 12 homozygot polymorphism were observed in study and control group respectively. The difference between two groups were statistically significant (p=0,04). There was no statistically significant difference between two groups for PAI-1 4G/5G polymorphisms (p=0,362). In subgroup analyses, statistically significant difference was found only in MTHFR C677T polymorphism in patients with GI cancer and with and without thrombosis (p=0,028). Conclusions: The studies investigating the relationship between genetic factors and thrombosis revealed controversial results. However, we found no genetic factor relevant to thrombosis other than MTHFR C677T polymorphism. Further studies investigating genetic and acquired factors in the development of the thrombosis in detail are warranted for documenting clearly the role of genetic polymorphisms. No significant financial relationships to disclose.
Abstract 18595: Efficacy of Vorapaxar is not Modified by Thienopyridine Therapy: Results from TRA 2°P-TIMI 50 Trial
Authors: Marc P Bonaca, Benjamin M Scirica, Eugene Braunwald, Harvey D White, Philip E Aylward, Peer Grande, Sabina A Murphy, David A Morrow
Journal: Circulation (2012)

Vorapaxar antagonizes the platelet protease-activated receptor (PAR)-1,the primary receptor for thrombin on human platelets. The addition of vorapaxar to standard therapy has been shown to reduce thrombotic events in patients with stable atherosclerosis. We investigated whether the efficacy and safety of vorapaxar in stable atherosclerosis were modified by thienopyridine therapy. METHODS: The TRA2P-TIMI 50 trial was a randomized, double-blind, placebo controlled trial of vorapaxar 2.5 mg daily in 26,449 patients with established atherosclerotic vascular disease. Patients were stratified at randomization based on planned use of thienopyridine therapy. The first efficacy endpoint was a composite of cardiovascular death (CVD), MI, or stroke and the primary safety endpoint was GUSTO moderate or severe bleeding. Analyses were adjusted for qualifying disease state (MI, stroke, PAD). Treatment with ASA ≤ 162 mg was recommended. RESULTS: Thienopyridine was planned in 15,356 (58%) and ASA was used in 24,734 (94%) overall. Patients randomized to vorapaxar had similar significant reductions in the primary endpoint regardless of planned thienopyridine therapy (Figure, p-interaction 0.64) and after adjustment for qualifying disease state (MI, stroke, PAD). Findings were similar when patients were stratified by actual thienopyridine use at baseline (Figure, p-interaction 0.76) and at 18 months (p-interaction 0.99). GUSTO moderate or severe bleeding was increased with vorapaxar with no significant interaction in those planned for thienopyridine therapy (p-interaction 0.29) or those receiving thienopyridines through 18 months (p-interaction 0.71). CONCLUSIONS: Vorapaxar reduced CVD, MI, or stroke in stable patients with a history of atherothrombotic events and this effect was present whether or not vorapaxar was used with a thienopyridine. The increased risk of bleeding with vorapaxar was also similar regardless of thienopyridine therapy.
Chromosome arm 11q deletion predicts for neuroblastoma outcome: A Children’s Oncology Group study
Authors: E. F. Attiyeh, Y. P. Mosse, Q. Wang, C. Winter, D. Khazi, G. Hii, P. W. McGrady, K. K. Matthay, W. B. London, J. M. Maris
Journal: Journal of Clinical Oncology (2005)

6 Background: Chromosome arm 11q loss of heterozygosity (LOH) is a frequent occurrence in neuroblastoma. Previous studies have shown an association between 11q LOH and high-risk disease. However, these studies lacked the statistical power to conclusively analyze the prognostic impact of 11q LOH in multivariable analyses after adjusting for the currently used prognostic factors. Methods: We screened 917 primary neuroblastomas for chromosome 11 LOH with a panel of 4–8 microsatellite markers. Further mapping with up to 52 markers was performed on selected samples. The only inclusion criteria were availability of a constitutional DNA sample and outcome data. The sample set was representative of the overall neuroblastoma population. The median follow-up was 2.7 years. Results: LOH at chromosome arm 11q and unbalanced 11q LOH (loss of 11q material with retention or gain of 11p material) were present in 302 (33%) and 148 (16%) cases, respectively. The pattern of LOH for each tumor sample was consistent with the presence of a single region of deletion; all but two deletions involved 11q23. The majority of tumors with 11q LOH did not have MYCN amplification. Despite this, both 11q LOH and unbalanced 11q LOH were associated with high-risk disease (p<0.0001). Patients whose tumors showed unbalanced 11q LOH had 3-year EFS and OS of 50%±6% and 65%±5%, compared to 74%±2% (p<0.0001) and 83%±2% (p<0.0001) in those cases that did not (log-rank test). In a Cox proportional hazards model for multivariable analysis, unbalanced 11q LOH was independently prognostic for EFS after adjusting for stage 4, MYCN amplification, and Shimada histology (p=0.0068). Conclusion: Unbalanced 11q LOH is associated with aggressive neuroblastoma behavior and is independently prognostic for decreased EFS. Unbalanced 11q LOH status could be especially useful in determining whether a patient with locoregional neuroblastoma without MYCN amplification would benefit from more adjuvant chemotherapy. No significant financial relationships to disclose.
Abstract 14164: Intracoronary Compared with Intravenous Bolus Abciximab Application during Primary Percutaneous Coronary Intervention - 12 Month Follow-Up of the AIDA STEMI Trial
Authors: Holger Thiele, Jochen Wohrle, Rainer Hambrecht, Harald Rittger, Ralf Birkemeyer, Bernward Lauer, Petra Neuhaus, Oana Brosteanu, Peter Sick, Sebastian Kerber, Klaus Kleinertz, Ingo Eitel, Gerhard Schuler, Steffen Desch, Aida Stemi Investigators
Journal: Circulation (2012)

Background The AIDA STEMI trial compared i.c. versus i.v. abciximab bolus during primary PCI in ST-elevation myocardial infarction (STEMI) patients. At 90-day follow-up i.c. as compared to intravenous abciximab resulted in a similar 90-day rate of the primary composite clinical endpoint.1 However, there was a significant reduction in congestive heart failure. A longer follow-up is warranted. Here the 12-month data are reported. Methods and Results AIDA STEMI was a randomised, open-label, multicenter trial. Patients presenting with STEMI were randomly assigned in a 1:1 ratio to i.c. versus i.v. abciximab bolus during PCI with subsequent 12 h intravenous infusion. The primary efficacy endpoint was the composite of all-cause mortality, recurrent infarction or new congestive heart failure within 90 days. Secondary clinical endpoints were each individual component and included also a 12-month follow-up. Between July 2008 to April 2011, 2065 patients were assigned to intracoronary (n=1032) or intravenous abcixi...
Profiling of cytokines and angiogenic factors (C/AF) in head and neck (HN) cancer correlates circulating biomarkers with clinical outcomes following induction chemotherapy
Authors: L. A. Byers, M. S. Kies, W. N. William, J. Hu, J. J. Lee, A. El-Naggar, V. Papadimitrakopoulou, J. N. Myers, S. M. Lippman, J. V. Heymach
Journal: Journal of Clinical Oncology (2008)

6005 Background: 36 cytokines and angiogenic factors (C/AFs) were measured in HN patients on a Phase II induction chemotherapy trial to investigate connections between biomarker signatures and clinical outcomes. Methods: Previously untreated patients (n=47) received 6 weekly cycles of paclitaxel (135 mg/m2), carboplatin (AUC 2), and cetuximab (400 mg/m2 week 1; 250 mg/m2 weeks 2–6) followed by definitive local therapy. Eligible patients were stage T0–4, N2b/c/3, M0; PS 0–1; with any HN primary site. There were 12 complete and 34 partial responses (MS Kies, et al, 2006 ASCO Annual Meeting). Serum from 32 patients at baseline and after cycles 1 and 6 was analyzed in duplicate by multiplex bead assay. IGF-1 was quantified by ELISA. Factors that did not meet predetermined criteria were excluded or retested. Statistical analysis was performed to compare biomarkers between patients and time points. Results: Minimum follow-up was 2 years; 6 patients recurred. Unsupervised hierarchical clustering of baseline levels for 36 C/AFs identified two distinct patient subgroups. One subgroup (n=19) included all recurrences and was characterized by high levels of hypoxia-induced factors (ex., VEGF, IL-4, PDGF, IFN-α). Log-rank comparison of progression-free survival between subgroups had a p-value of 0.042. Patients who recurred had lower baseline IGF-1 (p=0.018) and higher GRO-α (p=0.033) by analysis of variance (ANOVA); they also differed in the degree to which IGF-1, NGF, and IL-7 (p<0.05) and GRO-α, IL-3, and IL-12 (p=0.05- 0.10) changed from pre- to post-treatment (by ordinary two-sample t-test). From the 10 C/AFs that changed most significantly (p≤0.01) across all patients following treatment, 6 biomarkers (IL-12, IL-18, CTACK, SDF-1α, G-CSF, and MPC-1) were selected as a classifier whose baseline levels predict recurrence by the stepwise (backward) model selection procedure based on Akaike's information criterion. Conclusions: C/AF profiling identified differences in circulating proteins in HN patients who relapsed. Immunohistochemical staining is being performed to compare levels of tumor proteins in related pathways. C/AF signatures will be validated in an independent patient cohort. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration Bristol-Myers Squibb, ImClone Systems Incorporated