tbuckley/cabot-search huggingface dataset:
Evidence of immunogenicity with the anti-idiotypic monoclonal antibody vaccine 1E10. Results from a phase I clinical trial in breast cancer patients
Authors: M. A. Castro, M. Guthmann, G. Cinat, C. Venier, R. Bitton, L. Koliren, A. M. Alvarez, L. Fainbom
Journal: Journal of Clinical Oncology (2005)

2561 BACKGROUND: 1E10 is a gamma type anti-idiotype monoclonal antibody (Ab2) that mimics the Neu-Glycolyl GM3 antigen. Ab2 is specific to an Ab1 MoAb designated as P3, which recognizes Neu-Glycolyl containing gangliosides expressed in human breast cancer (BC). METHODS: Twenty patients (pts) were enrolled in this phase I study: 16/20 with high risk BC (≥4 positive axillary lymph nodes), included after completion of adjuvant treatment, and 4/20 with metastatic BC (2 bone, 1 nodal and 1 skin). Pts were assigned at three dose level groups: 0,5 mg (7), 1 mg (6), 2 mg (7). Six intradermal injections of the vaccine (1E10 adsorbed on aluminum hydroxide adjuvant) were given at 2-week intervals (induction phase), followed by ten monthly doses until completing one year of treatment (maintenance). Those pts who completed the induction phase were evaluable for immunogenicity. RESULTS: 8 pts completed the study with no evidence of relapse or progression; 11 didn’t complete the protocol because of: progression (7), toxicity (3), other (1) and 1 pt is now on treatment. Severe hypersensitivity skin reactions were observed in 2 pts and one pt experienced a trasient loss of consciousness with uncertain relation to the vaccine. The immunologic results by dose level were as shown in table. CONCLUSIONS: Vaccination with 1E10 was feasible and relatively well tolerated. The vaccine induced a very specific and strong immune response to Neu-Glycolyl GM3, independently of dose escalation. Interestingly, 40% of the evaluable pts showed a specific cellular response (TH1), representing the first time that such immune response against a non-peptide antigen is reported. Although these immunologic results are encouraging, larger studies are needed to define the clinical benefit of 1E10 in BC pts. No significant financial relationships to disclose.
Critical evaluation of the role of oxaliplatin- and irinotecan-based regimens as first-line chemotherapy in advanced colorectal cancer (CRC)
Authors: C. Carnaghi, L. Rimassa, M. Zuradelli, E. Morenghi, V. Torri, M. C. Tronconi, T. Pressiani, A. Santoro
Journal: Journal of Clinical Oncology (2006)

13562 Background: Until recently, 5-fluorouracil (5-FU) has been the mainstay of treatment for advanced CRC. In the last years, irinotecan and oxaliplatin have been shown to improve survival in combination with 5-FU. It is unclear if this improvement requires the use of these agents as first-line treatment or their sequential use during the course of disease. Methods: In order to assess the impact on prognosis of the first-line chemotherapy regimen, we retrospectively reviewed the outcome of all patients (pts) with advanced CRC treated at our insitution from May 1997 to December 2003. During this period our standard first-line chemotherapy moved from 5-FU and folinic acid (FA) to FOLFIRI to FOLFOX regimens. We analyzed changes in overall survival over time according to administered treatments. Results: From May 1997 to December 2003, 376 consecutive pts with advanced CRC were treated at our institution, 118 from 1997 to 1999, 135 from 2000 to 2001, 123 from 2002 to 2003. Patient characteristics did not vary over time for the 3 cohorts: median age was 62 years (range 26–83), 58% of pts were male, 72% had single metatastic site, liver was the main disease site (72%). In the first cohort (1997–99) the standard first-line treatment was 5-FU/FA, in the second (2000–01) FOLFIRI, and in the third (2002–03) FOLFOX. The number of pts who underwent 1, 2 o 3 lines of treatment for metastatic disease was similar for the 3 cohorts. The median overall survival was 21.4 months (95% CI 19.3–23.3). As shown below, no statistically significant differences were observed among the cohorts. Conclusions: Our retrospective analysis shows that the use of oxaliplatin and irinotecan has pushed the overall median survival to 21 months. The outcome of pts has been similar during the period 1997–2003 despite the shift in standard first-line treatment from 5-FU/FA to FOLFIRI to FOLFOX. These results are reasonably due to the sequential use of all the active regimens. [Table: see text] No significant financial relationships to disclose.
Treatment for patients with multiple myeloma complicated by renal failure by thalidomide-based regimens.
Authors: Y. Seol, J. Chung, B. Kwon, M. Song, Y. Choi, H. Shin, S. Kim
Journal: Journal of Clinical Oncology (2010)

e13093 Background: Thalidomide has been shown to be highly effective and to rapidly induce tumor response in patients with multiple myeloma. Moreover, thalidomide is a convenient oral and relatively inexpensive agent that is only minimally excreted through the kidneys. However there is limited data regarding the reversibility of renal failure, the kinetics of serum creatinine, and the safety of thalidomide when administered to newly diagnosed multiple myeloma and renal failure. Methods: We evaluated 29 consecutive patients with newly diagnosed multiple myeloma and renal failure, defined as a serum creatinine ≥2 mg/dl. All patients received thalidomide with dexamethasone or in combination with cyclophosphamide. Results: Reversal of renal failure was documented in 55% of all patients and the median time to reversal was 24 days (range, 4-132). Moreover, 13 patients (45%) had 50% decrease in serum creatinine and the median time to decrease was 36 days (range, 4-120). Some decrease of creatinine was documented in 90% of patients. The objective response rate was 66%. Toxicities were similar to those seen in myeloma patients without renal failure. Conclusions: Thalidomide- based regimens result in high rates of renal function restoration in patients with newly diagnosed myeloma renal failure complications. Morever, the toxicity and efficacy of thalidomide based regimens in myeloma patients with renal failure similar to those observed in patients without renal failure. Further studies will more formally evaluate the impact of thalidomide based regimens in this patient population. No significant financial relationships to disclose.
Metastatic uterine leiomyosarcomas: A single sarcoma center experience.
Authors: O. Merimsky, R. Bernstein-Molho, V. Soyfer, D. Grisaru
Journal: Journal of Clinical Oncology (2010)

e20510 Background: Uterine leiomyosarcoma (LMS) is a rare disease and, when recurs or metastasizes, can rarely be cured. The objective of this retrospective study was to summarize our experience in treating a large cohort of patients with recurrent or metastatic uterine LMS. Methods: Women diagnosed with recurrent or metastatic uterine LMS were identified retrospectively in our database between 2000 and 2007. Relevant clinical data were analyzed. Results: Thirty patients with median age of 56 were treated, six were lost to follow-up but their disease status was updated. Twenty patients were initially diagnosed with localized disease; ten of them received adjuvant RT after hysterectomy and other two had adjuvant chemotherapy and radiotherapy, with doses of 27-50.4 Gy. Two of the patients had evidence of progressive disease within 2 months from the end of adjuvant radiotherapy. Median disease-free interval of these twenty patients was 5.5 months and overall survival (OS) is 28 months, while nine of them are still alive with average follow up of 36.4 months (range 25-59.4). Median OS of ten patients with initially discovered metastatic disease is 19 months; while five of them are still alive with average follow up of 25 months (range 8-51). Doxorubicin-based therapy produced a 27% response rate; gemcitabine ± docetaxel achieved only 1/9 (11%) partial response and 67% stable disease when used as first line therapy. Three out of five patients (60%) treated with trabectedine (Yondelis) as second or third line of therapy achieved stabilization of their disease for at least 4 months. Ten patients underwent at least one surgical resection of pulmonary or extrapulmonary metastases after chemotherapy induction and another one had three metastasectomies without induction chemotherapy. In this group median OS was 42 months (range <8.1-59.4), 2- year survival was 82% and 3-year survival − 55%. Conclusions: Very few patients with recurrent or metastatic uterine LMS can be curatively treated. The impact of modern multimodal therapy, combining chemotherapy with aggressive surgery in selected patients may be significant in prolonging survival of women with this fatal disease. No significant financial relationships to disclose.
Chfr methylation as a marker of taxane sensitivity in breast cancer
Authors: A. J. Montero, L. Shen, V. Valero, J. P. Issa
Journal: Journal of Clinical Oncology (2004)

9583 Background: Checkpoint with Forkhead associated domain and RING finger (Chfr) is a novel cell cycle chekpoint gene, which prevents cell entry into metaphase in response to mitotic stress. Inactivation of Chfr by promoter methylation has been reported in various cancer cell lines, as well as in primary colorectal and lung cancer. Sensitivity to both docetaxel and paclitaxel in colon cancer cell lines has been correlated with hypermethyation of this gene. Conversely, colon cancer cell lines without significant CHFR methylation are more likely to survive treatment with taxanes. Methods: Primers for PCR were designed to evaluate promoter methylation of Chfr within 100 bases from the transcription start site. Pyrosequencing analysis was performed on 9 different breast cancer cell lines to evaluate Chfr methylation. Findings were then correlated with drug-sensitivity data for paclitaxel from the NCI-60 database. Results: Methylation of Chfr was found in 1 of the 8 breast cancer cell lines evaluated. This cell line, MDA-MD 435, of the breast cancer lines in the NCI-60 database is the most sensitive to paclitaxel with a log GI50 of −8.602. Conclusions: Inactivation of the Chfr gene by methylation is an important mediator of taxane sensitivity in breast cancer. Further study is warranted in primary breast tumors of patients treated with neoadjuvant based taxane therapy to ascertain whether methylation correlates with a pathologic complete response. No significant financial relationships to disclose.
Ramipril research papers are retracted over faked data
Authors: Michael McCarthy
Journal: BMJ (2015)

Two papers that reported that the blood pressure drug ramipril was beneficial in patients with intermittent claudication due to peripheral artery disease have been retracted after an investigation found that data were fabricated by the studies’ lead author, Anna A Ahimastos, a researcher at the prestigious Baker IDI Heart and Diabetes Institute in Melbourne, Australia.

The first paper,1 published in JAMA in …
Predicitve factors for neoadjuvant chemotherapy in locally advanced breast cancer
Authors: M. A. Perez, J. Ruiz, H. Astudillo, M. Silva, J. Silva, M. A. Pluma
Journal: Journal of Clinical Oncology (2004)

863 Background: Neoadjuvant chemotherapy is the standard treatment for locally advanced breast cancer. Non randomized studies with various chemotherapy agents administered preoperatively demonstrated significant clinical response rates, but low rates of pathological tumor response. Our purpose is to identify the prognostic factors that determine response to preoperative chemotherapy. Methods: We made a retrospective analysis of 19 patients with Locally Advanced Breast Cancer (LABC), stages IIIA, IIIB (including inflammatory breast cancer) and IVA. All patients were treated in a multidisciplinary manner, 4 cylces of FAC standard dose, Radical Mastectomy, 4 cycles with taxanes, Radiotherapy and tamoxifen for ER/PR postive, from september 2000 to november 2003. The analysed variables were age, clincal stage (CS), histology, grade, Her2.neu, hormone receptors status, clinical response, pathologic response and Disease free survival. Results: Median age 47 (range 21–61). 3 CS IIIA, 10 IIIb, 4 Inflammatory and 2 IVa. 11 Ductal, 6 lobular and 2 mixed. 12 (63.15%) Grade II and 7 (36.84%) Grade III. Her2-neu postive 5 (26.31) and 14 (73.68) negative. Hormone receptors positive in 6 (31.57) pts and negative in 13(68.42%). Clinical Complete Response (cCR) 7 (36.84%) and 12 (63.15) Clinical Partial Response (cPR). Pathologic Response, Complete PR 3 (15.78%) Partial PR 16 (84.21%). Median follow up of 16 months (3–38m).We made comparisons by the chi square test finding no statistical significance between our varibles to predict rsponse to chemotherapy. Conclusions: None of our variables (clincal and molecular) predicted response or resistance to treatment. No significant financial relationships to disclose.
Vincristine (V), dactinomycin (A), and lower doses of cyclophosphamide (C) with or without radiation therapy for patients with newly diagnosed low-risk embryonal rhabdomyosarcoma (ERMS): A report from the Children’s Oncology Group (COG).
Authors: David Walterhouse, Alberto S. Pappo, Jane L Meza, John C. Breneman, Andrea Anita Hayes-Jordan, David Parham, Timothy P Cripe, William H. Meyer, Douglas S. Hawkins
Journal: Journal of Clinical Oncology (2012)

9509 Background: Intergroup Rhabdomyosarcoma Study (IRS) trials showed improved survival with VAC compared with VA for patients with Stage 1 Group III (non-orbit) or Stage 3 Group I/II ERMS (see table). In COG ARST0331, we hypothesized that VA in combination with lower doses of C (total cumulative dose=4.8 g/m 2 ) would produce the benefit of IRS-IV VAC with less toxicity for patients with Stage 1 Group III (non-orbit) or Stage 3 Group I/II low-risk ERMS. Methods: This single arm, non-inferiority, phase III study enrolled newly diagnosed patients with Stage 1 Group III (non-orbit) ERMS or Stage 3 Group I/II ERMS onto Subset 2. Therapy was 4 cycles of VAC followed by 12 cycles of VA over 46 weeks (total cumulative doses: V=54 mg/m 2 , A=21.6 mg/m 2 , C=4.8 g/m 2 ). The radiation therapy dose was 36 Gy for Group IIA patients, 41.4 Gy for Group IIB/C patients, and 50.4 Gy for Group III patients. From 2004–2008 girls with Group III vaginal RMS did not receive radiotherapy if a complete response was achieved with chemotherapy with or without delayed resection. The primary endpoint was failure-free survival (FFS), and results were compared with a fixed expected outcome. Results: With a median follow-up of 3.0 yrs, we observed 16 failures vs. 7.8 expected failures. Estimated 3-yr FFS was 63% (95% CI: 46%, 75%) (n=60), and overall survival (OS) was 84% (95% CI: 68%, 93%). Estimated 3-yr FFS was 46% (95% CI: 23%, 67%) for girls with non-bladder genitourinary tract ERMS (n=21) and 75% (95% CI: 53%, 88%) for all other Subset 2 patients (n=39). Conclusions: We observed suboptimal FFS of patients with Subset 2 low-risk RMS using reduced total cyclophosphamide (4.8 g/m 2 ). Results were complicated by the choice of no radiation therapy for girls with vaginal tumors. Future studies for low-risk RMS Subset 2 patients could investigate a dose of C between 4.8 and 26.4 g/m 2 with VA and local radiotherapy. [Table: see text]
627. Adenovirus Encoded Helicobacter pylori Neutrophil Activating Protein Promotes Maturation of DCs with Th-1 Polarization, Improved Antigen Presentation and Migration
Journal: Molecular Therapy (2014)

Adenovirus Encoded Helicobacter pylori Neutrophil Activating Protein Promotes Maturation of DCs with Th-1 Polarization, Improved Antigen Presentation and Migration
CYP2C19 Polymorphism and PON-1 Activity in NSTE ACS : Vorapaxar Effect in Relation to Clopidogrel Metabolism in the TRACER Trial
Authors: Pierluigi Tricoci, Edmond Chen, Megan L. Neely, Amelia Warner, Peggy H. Wong, Peter Sinnaeve, Lars Wallentin, Lisa K. Jennings, Robert F. Storey, Phillip E. Aylward, Harvey D. White, Frans Van de Werf, Paul W. Armstrong, Claes Held, Marco Valgimigli, Robert A. Harrington, John Strony, Kenneth W. Mahaffey, David J. Moliterno
Journal: Circulation (2013)

CYP2C19 Polymorphism and PON-1 Activity in NSTE ACS : Vorapaxar Effect in Relation to Clopidogrel Metabolism in the TRACER Trial
Human leukocyte antigen (HLA) DR4 is not associated with differences in overall survival (OS), progression free survival (PFS), or graft-vs-host-disease (GVHD) following allogeneic hematopoietic stem cell transplantation (allo HSCT) for myeloid malignancies
Authors: S. Gupta, C. Aggarwal, T. Hahn, S. Padmanabhan, P. McCarthy, M. Battiwalla
Journal: Journal of Clinical Oncology (2006)

6552 Background: HLA DR4 is associated with autoimmune disorders and with response to cyclosporine immunosuppression in T-cell Large Granular Lymphoproliferative Disorder (BJH 2003;123(3)). We have earlier reported association of DR 15 positivity with decreased acute GVHD (aGVHD) in patients undergoing allo HSCT for myeloid malignancies (Blood, 2005 Nov 10;Epub). Therefore we investigated the role of HLA DR4 on graft-versus-leukemia effect and GVHD in HLA-matched allo HSCT performed for myeloid malignancies. Methods: A retrospective review of 119 consecutive related and 48 consecutive unrelated allo HSCT patients (pts) treated between 1992 and 2003 at RPCI was performed to investigate the influence of HLA DR4 on OS, PFS and the incidence of grade 2–4 aGVHD and chronic GVHD (cGVHD). HLA DR B1 locus typing was determined by either molecular (n=108) or serologic (n=59) methods. The proportion of patients with one or two HLA DR4 antigens was 26% (43/167) which is similar to the range seen in general Caucasian population. Pt characteristics included: AML (n=84), CML (n=63), and MDS (n=20); median age 43 years (range 11–66); Male (n=104), Female (n=63); Caucasian (&gt;95%); Total Body Irradiation (TBI) conditioning regimens (n=124); Busulfan (Bu)/Cyclophosphamide (Cy) (n=22), Bu/TBI (n=27), Cy/TBI (n=13), Etoposide/Cy/TBI (n=84), or other combinations (n=21). Results: There was no difference in OS and the PFS between the HLA DR4 positive vs negative groups in any disease or donor subgroups (p=0.4 and 0.6). GVHD prophylaxis was similar in the two groups but aGVHD and cGVHD incidence was not different in the two groups (p=0.8 and 0.9) Conclusions: HLA DR 4 is not associated with differences in GVHD or outcomes unlike the previous finding that HLA DR15 is associated with decreased acute GVHD in myeloid malignancies. These results suggest that there are differential effects of HLA DR antigens on the incidence of GVHD and outcomes in myeloid and lymphoid malignancies. Understanding these differences may facilitate the design of pt specific GVHD prophylaxis following allo HSCT. No significant financial relationships to disclose.
Randomized, phase III trial comparing liposomal platin with cisplatin in patients (pts) with advanced squamous cell carcinoma of the head &amp; neck (SCCHN) regarding safety and efficacy profiles
Authors: D. Luftner, S. Siepmann, J. Christian, D. Pollmann, G. Pecher, K. D. Wernecke, K. Possinger
Journal: Journal of Clinical Oncology (2006)

5564 Background: Based on a metanalysis of &gt; 16,000 patients (Bourhis, ASCO 2004), cisplatin emerges as the essential agent for the treatment of advanced SCCHN. However, its clinical use is impeded by its severe adverse reactions, as renal toxicity. In a randomized, phase III trial we replaced conventional cisplatin by a liposomal formulation of cisplatin (lipoplatin) and compared the safety and efficacy profiles. Methods: The study was designed for two treatment arms: A: 100 mg/m 2 /d lipoplatin (d 1,8,15) plus 1,000 mg/m 2 /d 5-FU (d 1–5) q3w for 6 cycles; B: 100 mg/m 2 /d cisplatin (d 1) plus 1000 mg/m 2 /d 5-FU (d 1–5) q3w for 6 cycles. Main inclusion criteria selected pts with primary metastatic, relapsed or progressive SCCHN between 18–75 years and creatinin clearance &gt;50ml/min. Main endpoints for this interims analysis were hemato- and nephrotoxicity. First response data were collected. The study was designed for non-inferiority. Results: Out of 41 randomized pts, 30 pts are evaluable for toxicity (15 pts for every arm) and 27 pts (15 pts for lipoplatin, 12 pts for cisplatin) for outcome. In the cisplatin arm hematotoxicity was more frequent (leucopenia grade I/II: 5 pts, grade III/IV: 3 and 1 pts vs 5 pts with grade I/II in the lipoplatin arm). The rate of anemia was similar between the treatment arms. A total of 11 pts in the lipoplatin arm experienced renal toxicity grade I/II as measured by a reduction of the creatinine clearance and 12 pts in the cisplatin arm (grade I/II: 7 pts; grade III: 5 pts). No renal toxicity grade III was developed in the lipoplatin arm until now. Outcome was as follows: lipoplatin arm: PR: 1 pt; SD: 6 pts; PD: 8 pts; cisplatin arm: PR: 7 pts; SD: 3 pts; PD: 2 pts. Thus, the non-PD pts (PR or SD) is 7/15 (47%) in the lipoplatin arm vs 10/12 (83%) cases in the cisplatin arm. Conclusions: Liposomal platin seems to reduce both the hematological and non-hematological toxicity profiles as compared to conventional cisplatin to a clinically relevant extent. As patients with advanced SCCHN have an increased risk of renal toxicity due to poor hydration, the observed reduction of side effects will influence the chance to preserve the dose density of chemotherapy, and thereby, the efficacy of treatment. No significant financial relationships to disclose.
mTOR inhibition is a rational target for the treatment of endometrial cancer
Authors: B. M. Slomovitz, W. Wu, R. R. Broaddus, P. T. Soliman, J. Wolf, C. C. Sun, D. C. Bodurka, D. M. Gershenson, K. H. Lu
Journal: Journal of Clinical Oncology (2004)

5076 Background: The finding of PTEN mutations in 40–60% of endometrial cancers suggests this pathway is important in the pathogenesis of this disease. Loss of PTEN leads to constitutive activation of AKT, which in turn leads to up-regulation of the mammalian target of rapamycin (mTOR). mTOR inhibition leads to decreased activation of the p70s6 kinase (S6K), a downstream protein directly and indirectly associated with cell proliferation. Currently, several mTOR inhibitors are under clinical investigation for the treatment of cancer. The purpose of this study is to evaluate the expression of mTOR and S6K in a series of endometrial cancers. Methods: Immunohistochemistry was performed using sections of tumors from 95 patients: 39 with endometrioid endometrial carcinoma (EEC), 37 with uterine serous carcinoma (USC), and 19 with recurrent endometrial cancer (REC). Sections were stained with commercially available antibodies for phosphorylated (phospho-) mTOR and phospho-S6K. Positive expression was defined as moderate (2+) to strong (3+) staining in >20% of the tumor cells. In addition, western blot analysis was performed on 5 endometrial cancer cell lines (HEC-1-A, HEC-1-B, Ishikawa, KLE, RL95–2) to determine the presence of mTOR and phospho-mTOR. Results: Phospho-mTOR expression was observed in 53% (50/95) of the tumors. Phospho-S6K expression was observed in 69% (66/95) of the tumors. 46% (18/39) of the EEC, 62% (23/37) of the USC, and 47% (9/19) of the REC expressed phospho-mTOR. 62% (24/39) of the EEC, 68% (25/37), and 89% (17/19) of REC expressed phospho-S6K. There was an association between mTOR and S6K expression (p=0.06). In addition, all of the cell lines expressed mTOR and 4 of 5 (80%) expressed phospho-mTOR (HEC-1-A, HEC-1-B, KLE, RL95–2). Conclusions: Phospho-mTOR and phospho-S6K are expressed in most endometrial cancers. There is an association between expression of mTOR and S6K. In addition, mTOR and phospho-mTOR are present in endometrial cancer cell lines. These results suggest that mTOR inhibitors may be useful for the treatment of endometrial cancer. We are initiating a phase II trial evaluating an mTOR inhibitor for the treatment of recurrent endometrial cancer. No significant financial relationships to disclose.