tbuckley/cabot-search huggingface dataset:
ZD1839 for the treatment of heavily pretreated non-small cell lung cancer
Authors: Y. L. Wu, X. Yang, J.-J. Yang, Y.-J. Huang, G. Chen, L.-J. Gu
Journal: Journal of Clinical Oncology (2004)

7341 Background: To evaluate the efficacy of ZD 1839 (Iressa) in terms of response rate, time to progression (TTP), and overall survival (OS) time for heavily pretreated non-small cell lung cancer (NSCLC). Methods: Patients had either stage IIIB or IV NSCLC for which they had received at least 1cycle chemotherapy regimen or radiotherapy received ZD1839 at a daily dose of 250 mg until disease progression. Results: From July 2001 to Oct. 2003, 44 patients were enrolled onto the study. The patient characteristic was male : female = 36 : 8; Adenocarcinoma : Squamous : other = 35: 7: 2 and stage 4 : 3=37: 7. Median chemotherapy cycles was 5 cycles and median follow-up time = 13.5 months. The overall disease control rate was 86.4% (completely response [CR], 11.3%; partial response [PR], 43.2%; stable disease [SD], 29.5%), median TTP was 5 months, 1-year survival 37.2% and median OS was 203 days. Median symptom improvement was 9 days. The most failure was brain metastasis in death cases (9/24, 37.5%). There were no significant differences between the male and female in rates of symptom improvement, TTP and survival. Most frequent side effects were rash and diarrhea that were well-tolerated. Conclusions: According to these data, ZD1839, a well-tolerated oral EGFR-tyrosine kinase inhibitor, had a good efficacy, toxicity, and symptom outcome in patients with heavily pretreated NSCLC. No significant financial relationships to disclose.
Assessment of the effectiveness of survivorship care in breast cancer patients.
Authors: Leah L. Dietrich, Mohammed Al-Hamadani, Chris Meyer, Alexandra Watral, Angela Smith
Journal: Journal of Clinical Oncology (2014)

123 Background: After the IOM report “From Cancer Patient to Cancer Survivor - Lost in Transition” was issued, there was a widespread call to develop Survivorship programs. Few studies have evaluated the effectiveness of these programs. Prior studies have focused on perceptions of, or preferences for, certain models of survivorship care. Therefore, our goal was to retrospectively evaluate our effectiveness based on patient perception, quality of life (QOL) and compliance with NCCN guidelines for follow-up. Methods: Eligible patients completed all of their breast cancer treatment at GHS. Surveys were sent out to evaluate patient knowledge and QOL. Chart review was conducted to assess NCCN compliance. Survivorship clinic attendees and non-attendees were matched for age and disease stage for comparison purposes of the outcomes (QOL, NCCN compliance, overall effectiveness) using descriptive statistics analysis. Chi-squares and t-tests/ANOVA statistical tests were used for categorical and continuous data significance respectively. Results: We found survivorship clinic patients (n=65) tended to perceive their concerns, in various categories, to be more adequately addressed than non-attendees (n=52), with significant differences in the areas of practical concerns and questions regarding late-term side effects. Categories in which there were no significant differences tended to be highly rated in both groups. There was also a significant difference in compliance with two NCCN guidelines for those attending survivorship. Additionally, women attending the survivorship appointment utilized supportive resources more than those who did not attend. Conclusions: Survivorship clinic attendees felt certain concerns were better addressed, were more compliant with NCCN recommended follow-up, and used supportive services more often than non-attendees. Statistically significant differences in other categories may be found in a larger sample size. These measures can be used to help us improve our survivorship services and for other institutions to measure quality and effectiveness of their programs.
Low Serum Super Concentration Predicts 90-Day Survival after Out-Of-Hospital Cardiac Arrest
Authors: V. Jalkanen, R. Yang, J. Vaahersalo, J. Kurola, E. Ruokonen, H. Huhtala, A. Kuitunen, V. Pettila, Jyrki Tenhunen
Journal: Intensive Care Medicine (2014)
Prognostic impact of MKI67 and MMP1 in node-negative invasive ductal and invasive lobular carcinoma of the breast
Authors: M. Schmidt, D. Boehm, C. von Toerne, H. A. Lehr, J. G. Hengstler, H. Koelbl, M. Gehrmann
Journal: Journal of Clinical Oncology (2007)

21102 Background: MKI67 and MMP1 mRNA, which might reflect the biological processes of tumor proliferation and matrix degradation, respectively, have been proposed as prognostic marker in invasive carcinoma of the breast. We compared the expression of both genes in invasive lobular versus invasive ductal carcinoma, which represent the most common histological breast cancer subtypes. Methods: MKI67 and MMP1 mRNA expression was determined by microarray analysis of fresh frozen tumor tissue of 118 patients with invasive ductal and 39 patients with invasive lobular carcinoma. We compared the distribution of these markers between both histological subtypes as well as within each subtype between tumors from patients with or without subsequent distant metastasis or local recurrence by two tailed Mann-Whitney test. Results: MKI67 as marker of proliferation and MMP1 as marker of matrix degradation were significantly elevated in invasive ducal versus lobular carcinomas (p = 0.023 and p &lt; 0.0001, respectively). Furthermore, elevation of both markers were significantly associated with the occurrence of metastasis in ductal (p = 0.023 and p = 0.012) but not in lobular carcinomas (p = 0.986 and p = 0.366). In addition, no significant association was found between these markers and development of local recurrence in patients with ductal (p = 0.304 and p = 0.899) or lobular (p = 0.891 and p= 0.153) carcinomas . Conclusions: Our data suggest that differences exist between ductal and lobular carcinoma of the breast regarding both the expression and the prognostic impact of MKI67 and MMP1. Furthermore, the prognostic relevance of proliferation and matrix degradation was more important for the development of distant metastasis than for the development of local recurrence in ductal carcinoma emphasizing differences in the underlying biology of local recurrence and distant metastasis. No significant financial relationships to disclose.
An open label phase II trial of the Plk1 inhibitor BI 2536, in patients with sensitive relapse small cell lung cancer (SCLC)
Authors: L. Gandhi, Q. S. Chu, J. Stephenson, B. E. Johnson, R. Govindan, P. Bonomi, K. Eaton, H. Fritsch, G. Munzert, M. Socinski
Journal: Journal of Clinical Oncology (2009)

8108 Background: BI 2536 is a potent, selective inhibitor of polo-like kinase 1 (Plk1), a regulator of mitotic progression. BI 2536 demonstrated favorable tolerability and antitumor activity in phase I trials. We investigated the antitumor efficacy, safety and PK of BI 2536 in patients (pts) with sensitive relapse SCLC. Methods: This open label single arm phase II study followed a Gehan two-stage design. Primary objective was to determine the antitumor efficacy of BI 2536 in SCLC pts with disease recurrence ≥60 days after completion of first-line chemotherapy. 18 pts had to complete 2 courses to be evaluable for stage 1 analysis. In case of ≥2 partial or complete antitumor responses (RECIST criteria), stage 2 accrual would continue until 40 pts were entered. Patients received 200 mg BI 2536 as a 1h i.v. infusion on Day 1 every 3 weeks. Dose escalation to 250 mg (cycle 3 onwards) was encouraged in pts with &lt;Grade 2 drug related non-hematologic and &lt;Grade 3 hematologic toxicity. Results: 23 pts (14 female, 9 male, 21 extensive disease, 2 limited disease), median age 60 yrs (range: 35–77) were treated. All patients had disease recurrence &gt;60 days after completion of first-line therapy. Of 23 pts, no objective antitumor responses were observed, 7 had stable disease as best response, 14 had progression, 2 were not evaluable. A median of 2 courses were given, up to a maximum of 12 in 1 pt. The PFS rate at 3 months was 25%. Due to the lack of antitumor responses, trial accrual was terminated after stage 1. Overall, BI 2536 was well tolerated. Frequent AEs were neutropenia (48%), fatigue (39%), nausea (30%), anemia, vomiting, constipation (26% each), and thrombocytopenia (22%). Drug related grade 3/4 AEs were neutropenia (13%/26%), grade 3/4 thrombocytopenia (1 pt each), grade 3/4 anemia (1 pt each), grade 4 sepsis (1 pt), Grade 4 ARDS (1 pt) and Grade 3 fatigue (1 pt). PK analyses indicate that BI 2536 has high clearance (&gt;1,000 mL/min) and quickly distributes in multiple compartments in a large volume of distribution (&gt;1,000 L). Estimated elimination half-life was &gt;25 h. Conclusions: BI 2536 was well tolerated in relapsed SCLC pts, but demonstrated no convincing antitumor efficacy after stage I of the study. Therefore, BI 2536 will not be assessed further as a single agent in SCLC. [Table: see text]
Comparison of the biologic effects of two recombinant human interferons alpha (rA and rD) in humans.
Authors: M J Hawkins, E C Borden, J A Merritt, B S Edwards, L A Ball, E Grossbard, K J Simon
Journal: Journal of Clinical Oncology (1984)

IFN-alpha (rD) was investigated to determine the relationship between antiviral activity in vitro and the modulation of biologic effects in vivo. Eight patients with malignancy were given 15 and 45 micrograms weekly injections of IFN-alpha (rA) and IFN-alpha (rD). The frequency of side effects was much lower with IFN-alpha (rD) injections. This was objectively documented both in incidence of side effects (20 versus 45, p less than 0.01) and mean maximum temperature (1 degree C lower with IFN-alpha (rD), p less than 0.002). A bovine cell line, MDBK, was used to measure interferon concentrations in the serum. Geometric mean peak titers and time-to-peak titers were similar with the two recombinant interferon preparations. Although IFN-alpha (rD) has relatively less antiviral activity on human cells, its effect on the total granulocyte count, natural killer (NK) cell cytotoxicity, and 2'5'-A activity was comparable to IFN-alpha (rA). Mean NK cell percent specific 51Cr release was enhanced by both interferons (after 15 micrograms doses, mean percent NK cell cytotoxicity IFN-alpha (rD) preinjection, 10.5% +/- 2.3%; post-injection, 27.2% +/- 4.5%; IFN-alpha (rA), preinjection, 14.4% +/- 3.2%, postinjection, 25.1% +/- 5%). Species-specific antiviral activity of an interferon does not necessarily predict other biologic properties following in vivo administration.
Phase II clinical trial preliminary report: Cetuximab, gemcitabine and simultaneous radiotherapy for locally advanced head and neck cancer: Preliminary report
Authors: J. G. De La Garza, M. Granados, J. L. Aguilar, J. Lavin, G. Cabrera, F. Maldonado, A. Moran, J. Cruz, K. Luna, B. Segura, G. Olvera
Journal: Journal of Clinical Oncology (2006)

15502 Background: Previous studies with cetuximab in SCCHN demonstrate to be clinically beneficial. In the present study we wished to evaluate the efficacy and safety of a chemotherapeutic scheme using gemcitabine, radiotherapy and cetuximab for SCCHN. Preliminary report of 20 of 40 enrolled patients into a phase II clinical trial. Methods: inclusion criteria; histological confirmation of epidermoid carcinoma, ages 18 to 70, K &gt; 70%, normal renal, hepatic and haematologic functions, without previous treatment, surgically inoperable disease, or patients with operable disease that did not consent to surgery. All patients signed an informed consent form. Radiotherapy: 200 cGy/d/5/w until 70Gy were completed. Cetuximab: an initial dose of 400 mg/m 2 one week prior to initiation of radiotherapy, followed by 250 mg/m 2 weekly until completion of radiotherapy. Gemcitabine: 50 mg /m 2 weeks 1–2, 4–5 and 7. Results: 20 patients were enrolled (16m/4f) from november of 2004 to november of 2005, (5 oral cavity, 5 oropharynx, 8 larynx, 1 hypopharynx and 1 paranasal sinus). Mean age 56 yrs (33–75). Tumor staging: 7/III, 8/IVa and 5/IVb. One female was excluded, 19 completed the study and were evaluated. GR 17/19 (89.5%), CR 13/17 (76.5%) and PR 4/17 (23.5%). 2/19 NR (10.5%). CR of the 1ary tumor 15/19 patients (78.9%); CR 6/11 patients with lymphatic disease at diagnosis (54.5%), PR 3/19 (27.3%). Toxicity: mucositis g/III-IV 8/19 patients; rash g/III 4 patients. 2/19 did not complete treatment with chemotherapy due to mucositis but did with radiotherapy. No relationship was found between clinical response and the severity of the rash. One patient developed leukopenia g/III. 4 patients developed disphagia g/II, one has not resolved after 8 month follow up. Xerostomia g/II was 7/19 patients. Dermatological toxicity resolved by the end of the treatment. Mean follow up: 6 months, 1 patient which did not respond died and 1 patient with a PR recurred. Conclusions: The scheme is safe and effective with tolerable toxicity. In our previously reported experience, the addition of cetuximab to gemcitabine and radiotherapy does not increment local toxicity, statistical validation of these findings require the completion of the 40 patient study. No significant financial relationships to disclose.
Trends and progress in phase III clinical trials on targeted agents in advanced cancers.
Authors: T. Nguyen, S. M. Ueda, J. Shin, J. Tan, J. Hoff, B. J. Monk, K. Osann, D. S. Kapp, J. K. Chan
Journal: Journal of Clinical Oncology (2010)

e15543 Background: To identify trends and progress in phase III trials on targeted agents in advanced cancers over the last 12 years. Methods: All phase III clinical trials on targeted agents in advanced cancers were identified in PubMed, Cochrane Central Register of Controlled Trials, and BIOSIS from 1994 to 2006. Results: Of the 156 phase III clinical trials, 67 were identified from 1994-2000 and 89 from 2001-2006. 79 (50.6%) used biologics alone and 77 (49.4%) used a combination of biologics and chemotherapy. 139 (89.1%) were from multiple institutions vs. 14 (9.0%) reported from a single institution. Pharmaceutical companies, cooperative groups, research institutes, academic centers, and others were primarily involved in 31.4%, 24.4%, 19.9%, 18.6%, and 5.8% of studies, respectively. Over the two study periods, there was a significant increase in the percentage of trials involving more than 500 patients (9.1% to 37.1%; p < 0.001). Multiple vs. single institution participations were noted to increase over time (83.1% to 96.6%; p = 0.004). The percentage of trials involving pharmaceutical groups increased from 21.0% to 42.2% (p = 0.05). High attrition rates (> 20%) were noted in larger percentage of these trials over time (1.7% to 16.3%) (p = 0.027). The proportion of trials reporting a high response rate (> 60%) increased from 23.1% to 43.1% (p = 0.022). The proportion of phase III studies with positive outcomes also increased over time from 17.0% to 36.0% (p = 0.013). Conclusions: In phase III studies on targeted agents in advanced cancers, the number of patients enrolled per trial, multicenter vs. single institution trials, and pharmaceutical group involvement vs. academic center-based studies has increased significantly. Identifying the progress and trends of phase III clinical trials may have significant implications for the design of future clinical trials. No significant financial relationships to disclose.
First-line gefitinib for poor <i>PS</i> patients with EGFR mutations
Authors: K. Kobayashi, A. Inoue, K. Usui, M. Maemondo, S. Okinaga, I. Mikami, M. Ando, A. Gemma, S. Morita, K. Hagiwara
Journal: Journal of Clinical Oncology (2008)

8070 Background: We had previously reported several phase II studies using good performance status (PS) patients (pts) with advanced non-small cell lung cancer (NSCLC) harboring epidermal growth factor receptor (EGFR) mutations (JCO, 2006:24, 3340, BJC, 2006:95, 998, and 1483). This phase II study was undertaken to investigate the efficacy and feasibility of gefitinib for poor PS pts with EGFR mutations. Methods: The peptide nucleic acid-locked nucleic acid polymerase chain reaction clamp method (PNA-LNA PCR clamp) can detect EGFR mutations using cytology specimens such as sputum and pleural effusion (Cancer Res, 2005;65:7276). Chemonaïve advanced NSCLC pts with poor PS and EGFR mutations examined by the PNA-LNA PCR clamp were enrolled and received gefitinib (250 mg/day) alone. The response rate, progression-free survival, overall survival, PS improvement rate and toxicity profile were assessed prospectively. Sample size was decided to be > 25 pts to show the lower limit of 90% confidence interval (CI) > 50% of each of response rate and PS improvement rate. Results: Between February 2006 and May 2007, 30 patients were enrolled into the study, and 29 pts were treated with gefitinib except for an early death before the treatment (PS 3–4:22 pts, PS 1–2 and over 80 years old:7 pts; 7 males/22 females; median age:72; adenocarcinoma:27 pts; Stage IV:27 pts; exon 19 del:18 pts, L858R:10 pts and L861Q:1 pt). The overall response rate was 66% (90% CI, 51 to 80) and the disease control rate was 90%. And 79% (90% CI, 63 to 91) of the patients improved performance status. Especially, 65% of the patients with PS 3–4 at baseline improved to PS 0–1. The median progression-free survival, median survival time, and 1-year survival rate were 9.3 months, 17.8 months and 73%, respectively. No treatment-related death was observed. Conclusions: This is the first study suggesting that first-line gefitinib treatment provides high efficacy with acceptable toxicity in advanced NSCLC patients harboring EGFR mutations, even in those with extremely poor PS. Since there has hitherto been no standard treatment for these patients with short life expectancy other than best supportive care, examination of EGFR mutations is strongly recommended in this patient population because it identifies patients who may be salvaged by EGFR tyrosine kinase inhibitors. No significant financial relationships to disclose.
Concordance in <i>miR-221</i>, <i>miR-222</i>, and <i>miR-370</i> expression and advanced nodal metastases of gastric carcinoma
Authors: S. Lo, C. Wu
Journal: Journal of Clinical Oncology (2008)

11025 Background: MicroRNAs (miRNAs) are short, endogenous non-coding RNAs involved in repressing target genes, which may be associated with the pathogenesis of tumor and other disease. Gastric carcinoma (GC) is a worldwide disease and the extent of nodal metastasis influences outcome of GC patients. The alterations of miRNA have not been fully defined. This study aimed to identify the expression signature, the clinical implication and functional role of miRNA in GC. Methods: Stem-looped quantitative RT-PCR analysis, cluster analysis, lentivirus-transduced expression system, reporter system and functional assays were used in this study. Results: Initial screening using quantitative RT-PCR analysis and cluster analysis established a profile of 29 aberrantly expressed miRNAs in tumors. miR-125b, miR-221, miR-222 and miR-370, and miR-200c were further confirmed over- expressed and under-expressed, respectively, in 33 GC and 5 GC cell lines. There was a statistically significant correlation among the expression of miR-221, miR-222 and miR-370. GC cases having concordance in the expression of miR-221 and miR-370, as well as the expression of miR-222 and miR-370 had more advanced nodal metastasis in relation to the contrasting group. Cases having concordance in the expression of miR-222 and miR-370 also exhibited more the most advanced clinical stage comparing to the contrasting group. The lentivirus-transduced plasmids for exogenous expression of miR-221 and miR- 222 and reporter plasmids constructed by ligation of complimentary sequences of these miRNAs to the 3’-end of the lacZ reporter gene were generated for functional assays. The forced expression of miR-221 and miR-222 repressed LacZ expression by targeting the complimentary sequences in AGS cells. In vitro assays indicated that the forced expression of miR-221 and miR- 222 enhanced the neoplastic phenotypes of AGS cells. Conclusions: The aberrant expression of miR-221 and miR-222 may be associated with the progression of GC. Interception of these miRNAs could be beneficial for the control of GC. No significant financial relationships to disclose.
Effectiveness and patterns of bortezomib use in real-life practice: Results of VESUVE, a French cohort study.
Authors: A. Fourrier-Réglat, H. Eghbali, T. Facon, J. Fermand, O. Fitoussi, G. Marit, A. Grelaud, E. Bignon, J. Jove, N. Moore
Journal: Journal of Clinical Oncology (2010)

e18522 Background: Targeted therapies are a very important therapeutic progress in the treatment of multiple myeloma (MM). Bortezomib (BTZ), the first proteasome inhibitor, was registered in France in April 04 for third-line therapy and in April 05 for second-line therapy. To date, no evaluation of BTZ in a real-life setting has been conducted in France. The VESUVE cohort study aimed to describe the effectiveness and the patterns of BTZ use in a real-life setting. Methods: VESUVE is a cohort study, conducted in 60 French centres that included patients initiating BTZ between May 04 and April 06, using nominative hospital pharmacy dispensations. Among those identified, patients treated for MM were followed for 36 months. For each patient, demographic data, clinical characteristics of MM, and treatment data were collected from medical files using a standardized case report form. Response was assessed by an independent committee according to adapted International Myeloma Working Group criteria. Results: Among the 798 patients followed-up, mean age was 65.6 years and 53.3% were men. Immunoglobulin MM was reported for 83.5% (56.3% IgG, 25.1% IgA), light chain for 14.9%, and non-secretory for 1.6%. About one third (34.1%) had a ß2-microglobulin level of more than 3.5 mg/L. Cytogenetic exams were available for 340 patients, 35.0% had a deletion of chromosome 13. Most patients received BTZ in second-line (17.7%), third-line (33.3%), or fourth-line (21.1%) treatment. The median number of BTZ cycles was 4 (6.3% of the patients completed more than 8 cycles). At the onset of treatment, 75.7% of patients had a BTZ dose of 1.3 mg/m2, 42.9% received BTZ alone, 43.0% in association with dexamethasone. Among the 593 patients for whom response was assessed, the overall best response rate was 58.4% (2.2% CR, 13.2% VGPR, 43.0% PR). 35.4% had stable disease and 6.2% progressive disease. The overall survival rate was 61.1% at 1 yr, 42.2% at 2 yrs and 31.1% at 3 yrs. Conclusions: This observational study shows that conditions of use in real-life settings may differ from those of the summary of product characteristics, e.g. the number of cycles was lower than that recommended. Nevertheless, the overall response rate was close to that reported in clinical trials. No significant financial relationships to disclose.