tbuckley/cabot-search huggingface dataset:
Safety of a novel capecitabine dosing schedule when combined with lapatinib in patients with HER2-positive metastatic breast cancer refractory to trastuzumab
Authors: T. A. Traina, M. Theodoulou, K. Feigin, S. Patil, S. Geneus, S. Modi, M. Fornier, D. Lake, L. Norton, C. Hudis
Journal: Journal of Clinical Oncology (2009)

1131 Background: Capecitabine (C) is active in breast cancer and is usually dosed for 14 days (d) followed by a 7d rest (14 - 7). We described a mathematical method which predicts the optimal schedule for C to be 7d followed by a 7d rest (7 - 7) (Norton et al, Amer Assn Can Res. 2005). The MTD of C(7 - 7) is 2,000mg BID (Traina et al, J Clin Oncol. April 2008). Lapatinib (L) improves time to progression when added to C(14 - 7) in patients (pts) with HER-2-positive (+) metastatic breast cancer (MBC) that progressed after trastuzumab (T). To optimize this effective combination, we are testing C(7 - 7) + L in a phase II trial. Methods: Eligible pts have measurable, HER-2(+) MBC that has progressed after T. HER-2(+)=IHC 3+ or FISH&gt;2. Pts have normal LVEF by MUGA, ECOG performance status (PS) &lt;2 and normal organ function. &lt;3 prior chemotherapy (CRx) regimens are permitted. Prior fluoropyrimidine is excluded. Therapy (tx) consists of C (2,000 mg BID, 7 - 7) and L (1,250 mg, daily). Cycle length = 4 wk. Pts are evaluated for toxicity q4 weeks (wk), for response q12wk; LVEF by MUGA q12wk. Primary endpoint: response rate (RR). Secondary endpoints: toxicity, stable disease &gt;6 months, PFS. Using a Simon optimal 2-stage design, with alpha = 10%, power = 90% to discriminate between RR 10% and 25%, 21 pts will be accrued to the first stage. If &gt;2 pts respond, 29 additional pts will be enrolled. If &gt;7/ 40 pts respond, then C(7 - 7) + L will be considered worthy of further study. Results: As of January 5, 2008, 6 pts are enrolled and evaluable. Median (med) age 64 yrs (42–71), med ECOG PS 1 (0–1), ER/PR(+) 3, HER-2(+) 6, sites of MBC: bone (2), viscera (4), soft tissue (5). Med baseline LVEF 62% (51–68%). Prior tx: Adjuvant: CRx (5), hormone tx (3), T (3); MBC: CRx (2), hormone tx (1), T (3). After a med of 3 cycles (1–4), there were no grade 3, 4, or 5 events. Tx-related toxicity is: Gr 2 fatigue (1); Gr 1 AST (4), diarrhea (3), ALT (2), vomiting (1), hand-foot (1), fatigue (1). No withdrawls due to reduced LVEF. Two pts evaluable for response: PR = 1, SD&lt;6 mo = 1. Conclusions: Capecitabine (7 - 7) + lapatinib appears well tolerated compared to C(14 - 7)+L (Geyer et al). Additional safety and efficacy data is anticipated prior to this meeting. [Table: see text]
Comparison of Treatment Effects Measured by the Hazard Ratio and by the Ratio of Restricted Mean Survival Times in Oncology Randomized Controlled Trials
Authors: Ludovic Trinquart, Justine Jacot, Sarah C. Conner, Raphaël Porcher
Journal: Journal of Clinical Oncology (2016)

We aimed to compare empirically the treatment effects measured by the hazard ratio (HR) and by the difference (and ratio) of restricted mean survival times (RMST) in oncology randomized trials.We selected oncology randomized controlled trials from five leading journals during the last 6 months of 2014. We reconstructed individual patient data for one time-to-event outcome from each trial, preferably the primary outcome. We reanalyzed each trial and compared the treatment effect estimated by the HR with that by the difference (and ratio) of RMST. We estimated an average ratio of the HR to the ratio of RMST; an average ratio less than one indicates more optimistic assessments with HRs.We analyzed 54 randomized controlled trials totaling 33,212 patients. The selected outcome was overall survival in 21 (39%) trials. There was evidence of nonproportionality of hazards in 13 (24%) trials. The HR and RMST-based measures were in agreement regarding the statistical significance of the effect, except in one case. The median HR was 0.84 (Q1 to Q3 range, 0.67 to 0.97) and the median difference in RMST was 1.12 months (range, 0.22 to 2.75 months). The average ratio of the HR to the ratio of RMST was 1.11 (95% CI, 1.07 to 1.15), with substantial between-trial variability (I(2) = 86%). Results were consistent by outcome type (overall survival v other outcomes) and whether the proportional hazard assumption held or not.On average, the HR provided significantly larger treatment effect estimates than the ratio of RMST. The HR may seem large when the absolute effect is small. RMST-based measures should be routinely reported in randomized trials with time-to-event outcomes.
Formation of Larger Cell Aggregates by Transformed Cells: An In Vitro Index of Cell Transformation2
Authors: Anton F. Steuer, Robert C. Ting
Journal: JNCI Journal of the National Cancer Institute (1976)

Journal Article Formation of Larger Cell Aggregates by Transformed Cells: An In Vitro Index of Cell Transformation Get access Anton F. Steuer, Anton F. Steuer Search for other works by this author on: Oxford Academic PubMed Google Scholar Robert C. Ting Robert C. Ting Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 56, Issue 6, June 1976, Pages 1279–1280, https://doi.org/10.1093/jnci/56.6.1279 Published: 01 June 1976 Article history Received: 20 October 1975 Accepted: 24 December 1975 Published: 01 June 1976
Irinotecan (CPT-11) and Mitomycin-C (MMC) as second-line treatment in advanced gastric cancer patients. A phase II study of the Gruppo Oncologico dell'Italia Meridionale (GOIM)
Authors: F. Giuliani, E. Maiello, S. Molica, C. Battaglia, N. Gebbia, M. Di Bisceglie, G. Vinciarelli, G. Colucci
Journal: Journal of Clinical Oncology (2004)

4235 Background: Irinotecan (CPT-11) is active in the treatment of advanced gastric cancer (AGC) (Futatsuki K: JPN Cancer Chem. 1994, 21 (7) 1033–1038; Khone CH: Proc. Asco 1999, 18: 258). Mitomycin-c is traditionally considered active in AGC. CPT-11 and MMC demonstrated to be synergic in colture (Kano Y: Int. J. Cancer 1992, 50: 604–610). Taking in account these data the GOIM started a phase II study to evaluate the activity and toxicity of this combination in pretreated AGC patients. Methods: Pretreated AGC patients with PS ≥ 70- ≤ 100 (Karnofsky scale), age between 18–75 years, bidimensionally measurable disease, life expectancy more than 3 months, adequate bone-marrow, renal and hepatic function, written informed consent, entered into the trial. The two drugs were administered as follow: CPT-11 at the dosage of 150 mg/mq (120 mg/mq if age >70 years) as 90' iv infusion on days 1–8 and MMC at 8 mg/mq as short infusion immediately after CPT-11 on day 1. The cycles were repeated every 4 weeks. Up to now, 29 patients were enrolled. Their main characteristics were: sex (M/F) 18/11, median age 66 (range 42–75), median PS 80. The main sites of disease: liver 13, lymph nodes 10, local relapse 5, lung 3, peritoneum 5. Eleven patients had multiple sites of disease. Results: Twenty-four patients are evaluable for activity and toxicity; two are too early and three patients are not evaluable (two refused). One CR (4%) and 9 PR (37%), 4 SD (17%) and 10 PD (42%) were observed, for an overall objective response rate of 41% and a tumor growth control rate of 58%. The median time to disease progression was 5 months and the median overall survival was 10+ months. The main observed percent toxicity rate (G1–2 vs 3–4, NCI criteria) were: leukopenia 54/4, neutropenia 42/17, anemia 54/4, nausea/vomiting 42/4, diarrhea 33/0, mucositis 4/0, cholinergic syndrome 17/0. In 9 pts (37.5%) G-CSF was employed. Conclusions: The combination of CPT-11 and MMC is active and well tolerated in pretreated AGC patients; further studies will clarify its role also in untreated patients. No significant financial relationships to disclose.
Multi-center performance evaluation of a biochip designed to analyze the expression of 11q23/<i>MLL</i> abnormal fusion transcripts in acute leukemia
Authors: N. Maroc, A. Morel, C. Harrison, M. Griffiths, G. Mitterbauer-Hohendanner, S. Shurtleff, V. Fert, F. Hermitte, V. Castéras
Journal: Journal of Clinical Oncology (2004)

9577 Background: 11q23/MLL abnormalities are generally associated with unfavorable prognosis in acute myeloid leukemia (AML). More than 50 partners have been described for MLL, and 35 of these partners have been cloned and analyzed at the molecular level to date. The functional role of each specific fusion transcript on the progression and outcome of disease remains to be elucidated. We present here the results of an international multi-center study aimed at assessing the clinical performance of a new biochip based molecular device (MLL FusionChip™ kit) designed to confirm the 11q23 abnormality and identify the MLL fusion gene partner. Methods: Nine laboratories in 7 countries ran 4 sets of 5 assays. Each run included a control sample (positive cell line), 2 negative samples, and 2 positive samples. Sample inclusion criteria were made by current standard diagnostic procedures: MLL status of all samples were characterized by cytogenetics, FISH, and/or RQ-PCR, and RNA sample quality assessed prior to analysis on the MLL FusionChip. Results: Nine different partners were accurately identified, including rare cases such as AF17, AF10, MSF, and P300. Overall agreement between routine diagnostic analysis and the MLL FusionChip was >90%. Conclusions: A previous study showed the analytical performance of this oncodiagnostic device is consistent with its claimed use. Taken together, these results collectively demonstrate the MLL FusionChip provides reliable data that may enrich minimal residual disease (MRD) follow-up in the clinical setting. Further studies are necessary to evaluate the clinical utility of the molecular classification of acute leukemia, and whether additional molecular information acquired with this device will contribute to refinement of the 2001 WHO classification. Expected consequences may be enhanced patient stratification, expansion of personalized therapeutic approaches, and optimized use of molecular targeted-based therapeutics. No significant financial relationships to disclose.
Phase II study of VNP40101M in patients (pts) with acute myelogenous leukemia (AML) and high-risk myelodysplasia (MDS)
Authors: F. J. Giles, S. O’Brien, N. Vey, E. Feldman, D. Rizzieri, K. D. Khan, S. F. Bilgrami, G. Verhoef, G. Mufti, B. Johnson, J. Karp
Journal: Journal of Clinical Oncology (2005)

6541 Background: VNP40101M is a novel sulfonylhydrazine alkylating agent with significant activity in refractory AML. In a phase I single agent study of pts with relapsed/refractory leukemias, the DLT was prolonged myelosuppression, with minimal extramedullary toxicity (Giles. Clin Cancer Res. 2004;10:2908). Methods: A single agent phase II study of VNP40101M (600 mg/m2 IV on d1) is being conducted in two groups of pts: Group A- AML or high-risk MDS, age ≥ 60, no prior induction treatment; Group B- Adult AML in first relapse after CR < than 12 months. All pts receive hydroxyurea 30mg/kg q12hrs x 6 doses, d1–3. A second induction cycle is administered no earlier than d35 to pts with partial response or hematologic improvement; pts with CR or CRp (CR criteria with platelets < 10x109/L) receive consolidation at VNP40101M dose of 400mg/m2. Interim analyses at 1/3 and 2/3 of pt accrual are planned. Results: 101 pts were enrolled by Dec 1, 2004; 93 patients (A=60; B=33) are currently evaluable for toxicity and response at > 30 days from day 1 of treatment. Group A=50 elderly AML pts and 10 high risk MDS pts. Median age (range): A=71 yrs (54–84), B=59 yrs (29–84); male: A=65%; B=58%; ECOG PS 0, 1, 2: A=28%, 43%, 28%; B=48%; 39%; 12%. Cytogenetic risk categories are: A=0 favorable; 32 (53%) intermediate; 12 (20%) unfavorable; 16 (27%) unknown. B=1 (3%) favorable; 15 (45%) intermediate; 8 (24%) unfavorable; 9 (27%) unknown. Responses are observed in both groups. A: CR=13 (22%), CRp=3 (5%), ORR=27%; B: CR=2 (6%), CRp=2 (6%), ORR=12%. VNP40101M-attributable serious adverse events, excluding febrile neutropenia, bleeding and infection were rare. Toxicities included nausea, diarrhea, fatigue, fever, pain and dyspnea. 12 pts (13%) died before d30 (A=8; B=4); 2 pts died within 30d after cycle 2. Conclusions: VNP40101M has significant activity, producing objective response in 27% elderly high-risk MDS/AML and 9% poor prognosis first relapse AML pts. VNP40101M is well tolerated; severe drug-related non-hematologic toxicities are uncommon. An international prospective randomized comparison of VNP40101M plus ara-C versus ara-C for patients with first relapse of AML is underway. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Vion Vion Vion
Influence of tiotropium bromide (TB) on the severity of clinical, functional symptoms and health-related quality of life (HRQL) in COPD patients (pts)
Authors: Lyudmyla Konopkina, Tetyana Pertseva, Vitalii Berezovskyi, Bogdana Basina
Journal: European Respiratory Journal (2011)

Aim: To study influence of TB on the severity of clinical, functional symptoms and HRQL in COPD pts.

Materials and methods: We studied 24 pts in stable phase of COPD (age – 64,3±2,3 yrs), who used fenoterol/ipratropium bromide (Berodual-H), before and after 2-month's course of treatment with TB (Spiriva® HandyHaler). Measurements included clinical status (severity of cough score (1 – mild, 2 – moderate, 3 – severe), quality of mucus score (1 – low, 2 – moderate, 3 – high), severity of breathlessness MRC-score), spirometry, St.George's Hospital Respiratory Questionnaire (SGRQ).

Results: Results are presented in the Table.

View this table:



Conclusion: 1) 2-month's course of treatment of COPD pts with TB leads to more rapidly improvement of clinical status than of functional one; 2) symptoms score of SGRQ reflects clinical changes of COPD pts and may be use as an objective parameter during introductions of new treatment programs.
Possible Etiological Role of Virus Particles Detected in Rat and Monkey Mammary Tumors&lt;xref ref-type="fn" rid="FN1"&gt;1&lt;/xref&gt;
Authors: Harish C. Chopra, Herbert K. Oie
Journal: JNCI Journal of the National Cancer Institute (1972)

Type-C particles were isolated From a spontaneous mammary adenocarcinoma (R-35) of Sprague-Dawley rats. The virions were propagated in tumor cell cultures. Inoculation of concentrated cell-free virus and tumor tissue-culture cells intraperitoneally into newborn rats produced mammary adenocarcinomas. Serologically, this virus was unrelated to type-C particles of murine, avian, hamster, and feline leukemia viruses. It had a density of 1.16 g/cm8 and contained 60–70S RNA and RNA-dependent DNA polymerase. Recent evidence of this virus infecting lactating rat mammary-gland cells with oncogenic potentials suggests its etiological relationship to rat mammary cancer. Similar, but clearly not identical, particles were detected in a spontaneous mammary carcinoma of a rhesus monkey. In the tumor cells the virions developed intracytoplasmically (type A) and budded off extracellularly from the cell surface. The isolated virus is being propagated in monkey embryo cells and in human leukocytes (NC-37). The ultramorphology of long-term propagated virus exhibited eccentric nucleoids, thus resembling type-B particles of mouse mammary tumor virus both in its development and extracellular form. It had a density 1.16 g/cm3, contained 60-70S RNA, and demonstrated reverse transscriptase. Serologically, the virus did not cross-react with other oncogenic viruses or simian foamy viruses. Type-B morphology of this virus and its biochemical characteristics of oncogenic viruses suggest its etiological relationship to the monkey breast cancer.
Crucell: Biopharmaceuticals-As Human as They Get
Authors: GINA KIRSCHWEGER
Journal: Molecular Therapy (2003)

The production of recombinant insulin in genetically engineered bacteria in the 1970s marked the beginning of a new era in the pharmaceutical industry. Since then, biopharmaceuticals have become far more sophisticated, and more often than not the demands of producing complex drugs overtax the lowly prokaryotes. Today, producer cell lines derived from animal cells are used for large-scale production of vaccines, virus-based gene therapy vectors, and monoclonal antibodies and other bioactive proteins.
Survival update for the phase III study of pemetrexed vs docetaxel in non-small cell lung cancer (NSCLC)
Authors: F. Demarinis, S. Paul, N. Hanna, T. Chang Yao Tsao, S. Adachi, H. L. Lim
Journal: Journal of Clinical Oncology (2006)

7133 Background: Results from a large, randomized, phase III study of pemetrexed vs docetaxel as second-line treatment for advanced NSCLC indicated that pemetrexed, a novel multitargeted antifolate, has a median survival time (8.3 months) similar to that of docetaxel (7.9 months) with a more favorable safety profile [JCO 2004;22:1589–97]. This updated analysis reflects data available 23 months after the original analysis, which was performed Jan 2003 (after 519 deaths). Methods: Pts (n = 571) were randomized from March 2001 to Feb 2002 to receive either pemetrexed (500 mg/m 2 IV infusion), supplemented with vitamin B 12 injections and folic acid, or docetaxel (75 mg/m 2 IV infusion) on day 1 of a 21-day cycle. An unadjusted survival analysis was performed and a Cox multiple regression analysis (n = 532) was done to adjust for factors (other than treatment intervention) that affected survival including ECOG performance status (PS), disease stage, and time since last chemotherapy. Percent retention was performed using the Rothmann method. Results: The updated survival analysis (performed after 519 deaths) indicated similar median survival times for pemetrexed (8.3 months; 95% CI: 7.0–9.4) and docetaxel (8.0 months; 95% CI: 6.6–9.3), and comparable hazard ratios (HR) (original 0.99 [95% CI: .82–1.20] vs updated 0.97 [95% CI: .81–1.15]). Percent of docetaxel benefit over best supportive care retained by pemetrexed was similar in both analyses: original 102% (95% CI: 52%-157%) vs updated 106% (95% CI: 68%-163%). Cox multiple regression analysis again showed that the two drugs were similar in survival after adjusting for factors significantly associated with increased survival. Conclusions: These updated survival analyses consistently demonstrate that second-line pemetrexed has similar survival to docetaxel in pts with NSCLC. Given the continued finding of comparable therapeutic efficacy, pemetrexed may be considered a standard second line therapy. [Table: see text] [Table: see text]
Journal for immunotherapy of cancer reviewer acknowledgement 2015
Authors: Pedro Romero
Journal: Journal for ImmunoTherapy of Cancer (2016)

On behalf of the JITC Section Editors and Associate Editors, I wish to acknowledge with sincere appreciation the assistance of the following reviewers who generously contributed their time and efforts in 2015 in the appraisals of manuscripts submitted to the journal. These reviewers not only have been invaluable in assessing the merit of submitted studies but also, by their careful analysis and critique and their general and specific constructive recommendations, have often greatly enhanced the value of these manuscripts. The quality of JITC can be attributed in large measure to their dedication and we are sincerely grateful.
In vivo metabolic activity and transcriptional profiling in melanoma (MM) patients during sorafenib and dacarbazine (DTIC) treatment.
Authors: M. J. Barysch, M. B. Karpova, H. Steinert, D. Widmer, C. Burger, M. J. Okoniewski, K. Hoek, N. Maradan, R. Dummer
Journal: Journal of Clinical Oncology (2010)

8575 Background: The multi-tyrosine kinase inhibitor sorafenib affects the Raf/Mek/Erk and VEGF pathway. The therapy impact on in vivo metabolic activity and transcriptional profiling was investigated. Methods: Single-arm investigator-initiated pilot study enrolled 13 first-line stage IV MM patients (LDH > 1.1 ULN) with metastases accessible for repeated biopsies. Patients were treated with sorafenib (400 mg bid, day 1-56) and DTIC (1,000 mg/m2, day 14, 42). Primary endpoints were changes in glucose uptake (PERCIST 1.0), S100 and LDH serum levels. Secondary endpoints were determination of differentially expressed genes and alternative splicing events during treatment. PET/CT, serum S100, LDH and biopsies were taken on screening, day 10, 16, and 60. Transcriptional profiling was performed using Human Exon 1.0 WT microarrays (Affymetrix). Differentially expressed genes and alternative splicing events were determined by R-Bioconductor using exonmap, limma, stats and samr packages. Enrichment analysis was performed using Genego Metacore. Results: At day 60, 5 responders and 8 non-responders (clinical and metabolic) were observed. Glucose uptake was inversely associated with response (p = 0.003) with a significant decrease of S100 in responders (p = 0.01), but not of LDH (p = 0.8, 2-tailed Mann-Whitney test). Transcriptional analysis of day 10 biopsies detected PEG10, HIGD2A, TOM1L1 for responders, and GMGF, CD163, CD53 for non-responders as top differentially expressed genes. Glucose metabolism network provided the best tool for hierarchical sample classification into responders and non-responders, confirming the in vivo data. JAK, TGFbeta and PIK3 signaling pathways, xenobiotic metabolism, DNA repair and vascularization processes were upregulated in non-regressive, but stress-induced metabolism and transcriptional reorganization networks in regressive lesions. Conclusions: Reduced glucose uptake by MM metastases under sorafenib predicts tumor regression. Metabolic tumor response is associated with distinctive molecular signatures on the transcriptional level and may contribute to rational personalized treatment approaches in MM patients. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Bayer Bayer Bayer
Hormone replacement therapy (HRT) in women with previously treated primary breast cancer
Authors: A. Z. Bluming
Journal: Journal of Clinical Oncology (2004)

685 Background: To assess the incidence of contralateral or recurrent breast cancer among women prospectively treated with HRT after initial breast cancer diagnosis. Methods: A community-based prospective, single-arm, pilot study of HRT among 232 women with previously treated primary breast cancer. Results: Median duration of HRT is 73+ months (range 12–136+). Median interval from initial surgery to initiation of HRT is 57 months (range 2–361 months). Follow-up to date is 100%. Actual disease-free survival (DFS), disease-specific survival (DSS), & median duration of HRT by stage are: Seventy four patients have stopped HRT (32%), 37 because of breast cancer development (16%), 2 because of the development of non-breast cancers, 2 died of nonmalignant disease, 2 because of HRT-associated symptoms, 1 because of pulmonary emboli without clinical phlebitis, and 30 because of anxiety about taking HRT. Actuarial DFS to 20 years for T1N0 patients was 73% versus 56% for comparable T1N0 patients who did not receive HRT. Conclusions: No evidence to date of increased development, recurrence or of breast cancer-related death associated with post diagnosis HRT. No significant financial relationships to disclose.