tbuckley/cabot-search huggingface dataset:
Temozolomide and cisplatin (TP) vs temozolomide (T) in patients with advanced melanoma. A randomized phase II of the Hellenic Cooperative Oncology Group
Authors: D. Bafaloukos, D. Tsoutsos, H. P. Kalofonos, A. M. Dimopoulos, E. Briassoulis, G. Fountzilas, A. Polyzos, D. V. Skarlos, V. Georgoulias, H. Gogas
Journal: Journal of Clinical Oncology (2004)

7545 Background: Temozolomide (T) is an oral alkylating agent that produces methyl adducts at the 0.6 position of guanine. The methyl adducts are removed by the DNA repair enzyme AGAT. As demonstrated by in vitro studies, cisplatin (P) is able to down regulate the AGAT activity, so enhancing the antitumor activity of T. From previous phase I study the recommended doses of T were 200 mg/m2 daily on days 1 to 5 and 75 mg/m2 of P on day 1, respectively, every 4 weeks. We designed a randomized phase II study to evaluate and compare the activity and safety profile of the combination vs single agent T, in patients with advanced melanoma. Patients and Methods: From January 2000 to April 2002, 127 patients were enrolled on the study. Patient and tumor characteristics were well balanced between the 2 arms. Patients with cerebral metastases were included. Patients received T 200mg/m2 /day po for 5 consecutive days every 4 weeks or T+P 200 mg/m2 daily on days 1 to 5 and 75 mg/m2 of P on day 1. Results: Tumor responses (CR and PR) were seen in 16 patients (26%) in arm A and 19 patients (29%) in arm B. The median time to progression (TTP) was 3.6 months in arm A and 5.8 months in arm B. The median survival (OS) was 14.6 months in arm A and 12.4 months in arm B. The difference between treatment arms regarding objective response rates, TTP, OS were not statistically significant. Toxicity was comparable between the two arms for anemia, leukopenia, neutropenia, thrombocytopenia, fatigue, constipation and arthralias-myalgias. There was significantly more grade 3 and 4 emesis in the combination arm. Conclusion: No clear benefit in terms of response rates, median time to progression or overall survival was shown with the combination of T+P. Additionally, the combination was associated with higher incidence of grade 3 and 4 emesis. Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Schering-Plough Pfizer
One cycle of induction chemotherapy (IC) to select for organ preservation for patients (PTS) with advanced squamous carcinoma of the oral cavity (SCCOC)
Authors: S. Urba, F. Worden, T. Carey, D. Chepeha, M. Prince, T. Teknos, A. Eisbruch, J. Lee, G. Wolf, C. Tsien
Journal: Journal of Clinical Oncology (2005)

5555 Background: A previous trial at the University of Michigan demonstrated that one cycle of IC can select pts with advanced laryngeal cancer for organ preservation. Methods: Pts with advanced SCCOC received one cycle of cisplatin and 5-fluorouracil. Those who achieved 50% reduction of their tumor received concurrent chemoradiation; those with less than 50% response underwent salvage surgery. Chemoradiation consisted of 70 Gy (2 Gy fraction daily x 7 weeks) with concurrent cisplatin 100 mg/m2 every 3 weeks x 3 cycles. After chemoradiation, pts with a complete histologic response received 2 cycles of paclitaxel 175 mg/m2; those with residual tumor had salvage surgery. Endpoints were survival and rate of organ preservation. Results: Between 7/24/2000 and 3/29/2004, 18 pts were enrolled, and 18 were eligible. Sixty-one percent were male and 39% were female. Mean age was 59 (range 37–87). Stage III -28% and stage IV -72%. Two patients died immediately after IC, prior to direct laryngoscopy. Following 1 cycle of IC, 16 pts underwent evaluation. Nine pts (56%) had a greater than 50% response and received chemoradiation. All 9 underwent evaluation for histologic response. Three pts had persistent disease: 1 had salvage surgery, 1 was surgically unresectable due to locally advanced disease, and 1 refused surgery. Six pts (67%) were complete histologic responders (CHR). Five CHR underwent neck dissections following chemoradiation. Adjuvant paclitaxel was given to 3 CHR - 2 received 2 cycles and 1 received 1 cycle. Seven pts (44%) had less than 50% response to IC. Of these, 4 had surgical resection; 1 had surgery off study; 1was no longer a surgical candidate and 1 died prior to surgery. The median time to follow-up is 30 months. Nine pts are dead, 7 from local/regional disease (3 after chemoradiation, 2 after surgery following IC, and 2 following IC), and two from other non-cancer related causes. The 3-year overall survival is 47% (95% CI [23.4%, 71.4%]) and the 3-year disease-free survival is 68.2% (95% CI [38.1, 98.3]). Conclusion: Given the poor response to IC and high failure rates following chemoradiation, this approach to organ preservation is not recommended for pts with advanced SCCOC. No significant financial relationships to disclose.
Effect of figitumumab (CP-751871) on the pharmacokinetics of cisplatin and pemetrexed in patients with advanced non-small cell lung cancer (NSCLC).
Authors: D. Yin, M. Carpentieri, A. Gualberto, D. Li, L. G. Paz-Ares, J. R. Canon, J. Sanchez-Torres, K. J. O'Byrne, A. Bello
Journal: Journal of Clinical Oncology (2010)

e18046 Background: Figitumumab is a fully human IgG2 monoclonal antibody targeting the IGF-1 receptor (IGF-1R). The combination of figitumumab with cisplatin and pemetrexed was evaluated in a phase I trial in patients with advanced non-small cell lung cancer (NSCLC). The effect of figitumumab on the pharmacokinetics (PK) of cisplatin and pemetrexed was determined as part of the phase I trial. Methods: A total of 13 patients with NSCLC were administered 20 mg/kg of figitumumab, 75 mg/m2 of cisplatin, and 500 mg/m2 of pemetrexed via intravenous infusion in cycles of every 3 weeks. Patients received the combination therapy for a maximum of 6 cycles, with the option to continue treatment with single agent figitumumab upon chemotherapy discontinuation. Plasma PK of total cisplatin and pemetrexed were evaluated over a 24-hour period before figitumumab dosing in cycle 1 and after concomitant figitumumab dosing in cycle 2. The concentration–time data were analyzed by noncompartmental methods to determine PK parameters. Results: Figitumumab at the dose level evaluated was well tolerated when given in combination with cisplatin and pemetrexed. For cisplatin, although mean values for Cmax and AUC0-24hr in cycle 2 (in the presence of figitumumab) were respectively, 23% and 26% higher than for cycle 1 (in the absence of figitumumab), individual Cmax and AUC0-24hr values from both cycles were in a similar range. Based on preliminary pemetrexed PK data available from 10 of the 13 patients, the mean Cmax and AUC0-24hr in cycle 2 were approximately 16% and 21% higher than corresponding mean values from cycle 1, respectively. These findings should be viewed in the context of the high inter-patient variability (CV% up to 44%) for cisplatin and pemetrexed PK parameters. Conclusions: Concomitant administration of figitumumab with cisplatin and pemetrexed appeared to result in slight increases in systemic exposures of cisplatin and pemetrexed. The high inter-patient variability in cisplatin and pemetrexed PK parameters and the overall tolerability of the tested combination suggest that adjustment of the starting dose for the chemotherapeutics may not be necessary. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Pfizer Pfizer Pfizer Pfizer
Abstract #2341: Tumor explant animal model: Moving towards tailor-made therapy of renal cell carcinoma
Authors: Marco De Velasco, Motoyoshi Tanaka, Kazuto Nishio, Hirotsugu Uemura
Journal: Cancer Research (2009)

AACR Annual Meeting-- Apr 18-22, 2009; Denver, CO

At present, there is no means of predicting the response of an individual patient to a given drug, invariably some patients will respond whereas others will fail and many will experience adverse drug reactions. Recent advances in chemotherapy have introduced a battery of receptor tyrosine kinase and mTOR inhibitors targeting renal cell carcinoma (RCC). In this experiment, we apply a new in vivo model of \#8220;tailor-made chemotherapy\#8221; to determine an individual\#8217;s tumor response to multiple chemotherapeutic treatments to predict the right treatment option. We compared the treatment response form fresh surgically resected clear cell carcinoma transplanted into nude mice treated with bevacizumab (5 mg/kg i.p.) or RAD001 (5 mg/kg i.p. twice/week). We determined treatment efficacy by measuring tumor growth, morphology, angiogenesis and expression of associated signaling pathway markers by histology and immunohistochemistry. Treatment responses to bevacizumab or RAD001 based on tumor volumes are summarized below:$$table_{E0EECD69-52EC-47A7-8784-69EC2C674228}$$ Tumor response to bevacizumab coincided with tumor over expression of VEGFR-2 marked by decreased post-treatment microvessel density counts. Decreased p-MTOR and p-S6K levels characterized tumors responding to RAD001. Further experiments to evaluate more treatment options need to be conducted to validate its utility in the clinical setting.

Citation Information: In: Proc Am Assoc Cancer Res; 2009 Apr 18-22; Denver, CO. Philadelphia (PA): AACR; 2009. Abstract nr 2341.
Exhaustive prospective collection of new sarcomas: Report of an unexpectedly high incidence
Authors: F. Ducimetiere, A. Lurkin, D. Ranchere-Vince, P. Biron, M. Peoch, L. Istier, D. Salameire, P. Chalabreysse, J. Y. Blay, I. Ray-Coquard
Journal: Journal of Clinical Oncology (2007)

20513 Background: Sarcomas are rare malignant tumors reported to account for 1% of all adult tumors - respectively 1–3 per 100,000 persons per year for soft tissue sarcomas (STS) and less than 0.5 for bone sarcomas (BS). There are more than 50 histological subtypes of STS, each with its own clinical management. Within the context of an evaluation of medical practices, we decided to assess the medical management of all sarcoma patients seen in one year in the Rhone-Alpes (RA) region which represents 10% of the total French population. One of the secondary objectives was to assess the incidence of sarcomas. About 1,800 STS cases are diagnosed each year in France, hence 200 new sarcomas (STS, BS, visceral) were expected in the region. Methods: A prospective and exhaustive collection of pathology data was launched in direct collaboration with the network of pathologists in the RA region. All patients in primary care, above 15 years old, and diagnosed with sarcoma from March 2005 to Feb 2006 in RA were included. Collection comprehensiveness was checked. Results: In one year, 417 patients met inclusion criteria and were analyzed: 65% STS (n=270), 20% visceral sarcomas (Gastro Intestinal Stromal Tumor (GIST), uterine sarcomas) (n=84), 12% BS (n=49) and 3% undifferentiated malignant tumors (n=14). The most frequent histological subtypes were GIST (17% n=72), liposarcomas (17% n=71), leiomyosarcomas (9% n=38). 27% og sarcomas were not otherwise specified (NOS) (n=74). 5 patients were between 15 and 18 years old at diagnosis. Conclusions: The first year of inclusion showed an incidence of sarcomas twice higher than reported in the literature. French registris classify tumours per organ site, leading to an underestimation of the number of cases. This is partly due to the non-identification of GIST or uterine sarcomas. This study raises the question of a need for a national registry of these rare tumors. Similarly, a histological classification is necessary to obtain accurate and specific incidence rates. Financial support: Merck KGgA, Ligues Ain et Rhône, CONTICANET network. No significant financial relationships to disclose.
Increased in vitro phenol-soluble modulin production is associated with soft tissue infection source in clinical isolates of methicillin-susceptible Staphylococcus aureus
Authors: Robert Qi, Hwang-Soo Joo, Batu Sharma-Kuinkel, Nicholas R. Berlon, Lawrence Park, Chih-lung Fu, Julia A. Messina, Joshua T. Thaden, Qin Yan, Felicia Ruffin, Stacey Maskarinec, Bobby Warren, Vivian H. Chu, Claudio Q. Fortes, Efthymia Giannitsioti, Emanuele Durante-Mangoni, Zeina A. Kanafani, Michael Otto, Vance G. Fowler
Journal: Journal of Infection (2016)
Effect of radiation therapy on survival of patients with surgically resected retroperitoneal sarcoma: A population-based matched pair study.
Authors: A. Choi, J. Barnholtz-Sloan, J. Kim
Journal: Journal of Clinical Oncology (2010)

10082 Background: Although the only curative treatment for retroperitoneal sarcoma (RPS) is surgical resection, radiation therapy is frequently added. Currently no prospective randomized trial has measured the efficacy of neoadjuvant or adjuvant radiation therapy in patients with resected RPS. The purpose of this study was to determine the effect of radiation therapy on overall survival between propensity score-matched, surgically-resected RPS patients using the Surveillance, Epidemiology, and End Results (SEER) database. Methods: The study population consisted of SEER patients with histologically-confirmed RPS between the years of 1973 and 2006. Only patients who were coded with surgical resection were included. Exclusion criteria included multiple malignancies, distant metastasis, and unknown grade or stage. Univariate and multivariate logistic regression was used to identify covariates associated with radiation therapy. Cox regression analysis was used to determine associations of covariates with overall survival. Finally, propensity score methods were used to perform a survival analysis in patients who underwent surgery and radiation therapy matched with control patients who underwent surgery alone. Results: Prior to matching there were 762 patients (558 surgery only, 204 with radiation therapy). Factors independently associated with radiation therapy by multivariate analysis were: age (p=0.037), geographic region (p=0.041), grade (p=0.047), stage (p=0.003), and surgery type (p=0.01). Cox regression analysis demonstrated that age and tumor grade were independently associated with survival. Propensity scoring resulted in 317 pairs of patients who had surgery and radiation therapy matched with patients who had surgery alone. Survival analysis using both Kaplan Meier and matched pair analyses demonstrated no difference between patients receiving radiation therapy and those who did not (p=0.22). Conclusions: At present, patients with surgically-resected RPS entered into the SEER database who have received radiation therapy have not demonstrated a survival benefit as compared to surgery alone. No significant financial relationships to disclose.
Cancer stem cell gene signature identified from advanced stage papillary serous ovarian adenocarcinoma side populations
Authors: Laurent Ozbun, Vinod Vathipadiekal, Michael Radonovich, Cindy Pise-Masison, Deepa Saxena, Peter Hauschka, Samuel Mok, Michael Birrer
Journal: Cancer Research (2008)

AACR Annual Meeting-- Apr 12-16, 2008; San Diego, CA

5005 

Recent studies support the concept that cancer as a disease is driven by cancer stem cells and these are the cells that can both initiate tumor growth and then re-initiate tumor expansion after therapy. Hence an understanding of gene expression profiles of cancer stem cells may lead to improved therapies as well as novel insights into the cellular mechanisms of carcinogenesis in ovary. The aim of this study is to generate a cancer stem cell gene expression signature from isolated Side Populations of fresh ascites obtained from women with high-grade advanced stage papillary serous ovarian adenocarcinoma at the time of cytoreductive surgery at Brigham and Women's Hospital, Boston, MA. All patients had been diagnosed with ovarian cancer for the first time. All patient specimens were collected and studied under protocols approved by the institutional review board of the parent institution. Gene expression profiling using Affymetrix Human Genome U133 2.0 Plus microarray platform was performed on Side Populations (SP) and Main Populations (MP) isolated by Hoechst staining/FACS method. Array data was analyzed using BRB-ArrayTools. Paired T-test analyses (p<0.01) was utilized to identify differentially expressed genes between SP and MP. We identified 446 genes (138 up-regulated and 302 down-regulated) that were differentially expressed between all 10 SP and MP pairs. The microarray data was validated using quantitative reverse transcription polymerase chain reaction (qRT-PCR) on 19 randomly selected differentially regulated genes. 17/19 (89.5%) genes showed robust correlations between microarray and qRT-PCR expression data. The gene signature was enriched for genes in Gene Ontology biological processes of cell cycle, transport, apoptosis, regulation of translation/transcription, signal transduction, and cell proliferation. Further data mining for biologically relevant processes using Pathway Studio 5.0 identified genes overexpressed in SP that were related to functional cancer stem cell-like phenotypes of cell survival (PAWR), proliferation (EPHB), and apoptosis (AKT). WNT signaling pathway genes (FZD) were downregulated in SP, and genes implicated in normal stem cell  (NUP, ST3GAL, LTBP) were upregulated in SP. Taken together these results highlight the  function of the ovarian cancer SP gene signature. In conclusion, we generated an expression profile from SP enriched for cancer stem cells from ascites from ovarian cancer patients. The nature of the stemness of the SP gene signature was revealed by the identification of several stem cell-related genes and genes involved in the WNT -signaling pathway. These genes may be key players involved in the mechanisms controlling ovarian cancer stem cell functions, and may represent potential therapeutic targets.
Abstract P325: Quantifying the UK Social and Economic Benefits of Potential Policies to Reduce dietary Trans Fats: Modelling Study.
Authors: Jonathan Pearson-Stuttard, Kirk Allen, William Hooton, Peter Diggle, Simon Capewell, Martin O'Flaherty
Journal: Circulation (2015)

Background: Industrial trans fatty acids (TFAs) are commonly added to processed foods as a cheap way to increase shelf-life and enhance palatability. Natural TFA are found in small quantities in meat and dairy products. TFA substantially increase the risk of Coronary Heart Disease (CHD). The UK burden of CHD remains large, and unequal across socio-economic groups. TFA intake is also unequal, with largest intake in the most deprived groups. Methods: We modelled three policy options for reducing TFA in the English diet; a) increased labelling requirements resulting in partial voluntary reformulation; b) a ban on TFA in all restaurant &amp; take-away food, and c) a total TFA ban in all processed foods. We quantified health benefits for the period 2015-2020 for each policy (deaths prevented and life-years-gained -LYG). Analyses were stratified by age, gender, and socioeconomic quintiles (IMDQ). Mortality gains were linked to economic cost and benefits: direct healthcare costs, productivity loss averted, and informal care; government costs comprising legislative and monitoring; and costs to industry. Results were tested in a probabilistic sensitivity analysis. Results: The most effective UK policy in reducing CHD mortality from 2015-2020, would be a total TFA ban resulting in approximately 8,600 fewer CHD deaths [95% confidence interval 3,400 - 14,700] with a substantial inequality reduction of some 3,300 deaths [1,300 - 6,000]. Labelling with partial voluntary reformulation might result in approximately 2,500 fewer CHD deaths [1,100 - 4,600]; and an inequality reduction of some 800 deaths [300 - 1,400]. Whilst a TFA ban in restaurant and take-away food could yield approximately 2,200 fewer CHD deaths [900 - 3,800]; and an inequality reduction of some 700 [300 - 1,200]). All policies would be cost-saving for the government due to big reductions in health care costs. A total ban could achieve annual societal savings of approximately £96 million The labelling and restaurant and take-away bans might gain £12 - £14 million savings for, representing £8,600 to £3,700-£4,800 per QALY. Industry costs might reach some £210 million if extensive reformulations were required, but could be negligible if reformulations were absorbed into natural product reformulation cycles. Conclusions: Policies to reduce TFA consumption in the English population are a priority public health measure. As both TFA consumption and CHD burden are higher deprived groups, any TFA reduction will reduce inequalities in CHD mortality. A total ban on TFA in ALL processed foods would have the greatest coverage across social groups. It would also represent a good investment from a societal perspective. Policies with less comprehensive coverage would be correspondingly less effective at reducing mortality, inequalities and cost effective, but would still yield substantial health, and economic gains.
Two different schedules of docetaxel plus cisplatin as first-line therapy in advanced non-small cell lung cancer: A preliminary result from a randomized phase II study
Authors: S. Park, S. Bang, E. Cho, D. Shin, J. Lee
Journal: Journal of Clinical Oncology (2006)

7135 Background: There has been increasing interest in the use of a weekly administration of docetaxel as a way of reducing its hematologic toxicity. The purpose of this randomized study is to evaluate the toxicity and efficacy of docetaxel and cisplatin combination on two schedules in patients with previously untreated, advanced non-small cell lung cancer (NSCLC). Methods: Consenting patients with stage IIIB/IV or recurrent NSCLC were randomized to receive first-line chemotherapy with cisplatin 75 mg/m 2 on day 1, plus either weekly (35 mg/m 2 on day 1, 8, 15 of a 4-week cycle) or 3-weekly (75 mg/m 2 on day 1 of a 3-week cycle) docetaxel, both for up to 6 cycles. Objectives of this randomized phase II trial were response, toxicity and quality of life (QOL; measured with EORTC QLQ-C30). With a two-stage phase II design, the required number of patients was 39 per each arm. Results: Of 85 patients accrued, 71 patients were evaluable for response and 83 for safety. Baseline characteristics were well-balanced between the two arms: male (56 patients); median age (64 years); adenocarcinoma/squamous cell carcinoma (53/32); stage IIIB/IV/recurrent (12/63/10); ECOG performance status 0/1/2 (20/44/21). Median number of chemotherapy cycles was 3 (1–6) for both arms. Median dose intensities were docetaxel 88%, cisplatin 98% in weekly arm, and docetaxel 97%, cisplatin 98% in 3-weekly arm. The objective responses of weekly and 3-weekly arm were 38% (95% CI, 23–53) and 42% (95% CI, 27–57), respectively. There was significantly more grade 3/4 neutropenia (66% v 12%; P &lt; .001) and febrile neutropenia (40% v 7%; P &lt; .001) on 3-weekly arm but less grade 3/4 diarrhea (2% v 14%; P = .05) and severe skin/nail toxicity (5% v 29%; P = .003). No difference in the rates of treatment delay or dose reduction for both arms; however, 19% of day 15 docetaxel were omitted in weekly arm due to toxicity. Conclusions: Both weekly and 3-weekly docetaxel plus cisplatin appear to be active as first-line chemotherapy for advanced NSCLC, with different safety profiles. Updated results and QOL data, including a prolonged follow-up, will be presented. No significant financial relationships to disclose.