tbuckley/cabot-search huggingface dataset:
Current status of treatment of local recurrence and distant metastasis of triple negative breast cancer in Japanese population
Authors: T. Osako, R. Nishimura, Y. Okumura, M. Hayashi
Journal: Journal of Clinical Oncology (2009)

e11548 Background: Triple-negative breast cancers have an aggressive clinical history such as high incidence of visceral metastases, high rate of cerebral metastases, high rate of local recurrence, and early age of onset. However, there are limited long-term clinical data evaluating outcomes of locoregional and systemic therapy. The purpose of this study was to evaluate the clinical outcome of current therapy with TNBC retrospectively. Methods: From the medical records of our hospital, we retrospectively reviewed breast cancer patients whose three markers were available and describe the relationship between current therapy and clinical outcome. Results: Between 1998 and 2007, 1967 breast cancer patients were treated in Kumamoto City Hospital. Of 1967 patients, 264 (13.4%) were classified as TNBC by immunohistochemical technique. As of December 2008, with a median follow-up time of 31months, 53 patients (20.0%) with TNBC had locoregional recurrences or distant metastases (17 local recurrences, 15 nodal recurrences, 44 distant metastases). Forty out of 53 patients with recurrent TNBCs had adjuvant or neoadjuvant chemotherapy around surgery. Of 53 patients with recurrences, 31 had initial locoregional recurrence and 19 had initial distant metastases. Forty two patients had already been dead and common causes of death were lung metastases (19 patients), liver metastases (11 patients), and brain metastases (8 patients). Patients with TNBCs had a poorer 5 year-survival compared with those with non-TNBCs. Furthermore, patients with initial distant metastases had significantly poorer survival than those with initial locoregional recurrence (p=0.015). Focusing on chemotherapy, no specific cytotoxic agent had high effectiveness for recurrent TNBCs. However, patients who had responded to first regimens had a tendency to respond to the next regimens. Conclusions: TNBC had an aggressive behavior and poorer prognosis. However, TNBC with locoregional recurrence and benefits from the first regimen had favorable prognosis. Therefore, to distinguish the subgroup that respond to chemotherapy might contribute to the prolongation of survival of in TNBC. No significant financial relationships to disclose.
Plasma levels of SN-38 after co-administration of gefitinib and oral irinotecan in young and old mice
Authors: D. R. Cook, A. L. Merz, J. A. Zirrolli, M. Basche, D. L. Gustafson
Journal: Journal of Clinical Oncology (2006)

2062 Background: Preclinical studies demonstrate that irinotecan, approved for I.V. administration, is most effective when administered at frequent, low doses. This administration schedule would be most practical if irinotecan were administered orally. However, the oral availability of irinotecan is limited. Gefitinib can alter the oral bioavailability of irinotecan through inhibition of gut transporters (ABCG2) that prevent intestinal absorption. Thus, we evaluated a potential method for giving irinotecan at low doses on a protracted schedule by administering orally with gefitinib. Additionally, we hypothesized that the pharmacokinetics of irinotecan may differ in older versus younger adult mice. Plasma levels of SN-38 were measured and compared in old and young Balb/c mice given oral irinotecan alone or with gefitinib. Methods: Adult (2 months old) and older, retired breeder (10 months old) Balb/c mice were orally administered irinotecan at 10 mg/kg, 20 mg/kg or 40 mg/kg either alone (control) or with 30 mg/kg PO gefitinib daily for 5 days. On the fifth day, the mice were sacrificed approximately 4–6 hours after administering drugs. Plasma was collected and SN-38 levels determined by HPLC. Results: Nearly all mice receiving irinotecan with gefitinib had a 3 fold or more increase in the level of SN-38 in the plasma as compared to the mice receiving irinotecan alone. The older mice had a more dramatic increase. Conclusions: The plasma levels of SN-38 were consistently elevated in mice treated with oral gefitinib and irinotecan when compared to mice treated with irinotecan only. The more pronounced increase in SN-38 levels seen in the older mice may be due to changes in drug elimination with aging. The results indicate that oral irinotecan can be given in the presence of gefitinib resulting in higher levels of SN-38 in the plasma of young and older mice. Combination treatment allows easier titration of irinotecan in protracted dosing protocols evaluating efficacy and toxicity in older mice, and ultimately, humans. [Table: see text] No significant financial relationships to disclose.
Identifying best support care patients in an outpatient medical oncology unity: difficulties presented by training medical oncologists
Authors: M. D. Diz, G. Carelli, P. M. Hoff
Journal: Journal of Clinical Oncology (2008)

20613 Background: the large increase in the number of new drugs and technologies requires that oncologists correctly identify pts who are candidates for BSC, to provide appropriate symptom control and avoid futile aggressive treatments to poor prognosis patients who do not benefit from them. It may be particularly difficult to young medical oncologists in training to identify these patients. We conducted a survey between medical oncology residents to measure their perception of patients not able to receive chemo, radio or hormonal therapy for advanced cancer. Methods: For a week, questionnaires were answered by medical residents at the end of all outpatient consults in an adult, solid tumor medical oncology unit, in a public university hospital. A score was applied to identify patients that could be candidates to BSC, and this data was compared with the actual treatment given. Results: Questionnaires were answered in 200 (95,2 %) medical consults done in a week at the unit. Median age was 56.5 ± 14 years (range 18 - 89), 131 (65.5 %) patients were female and 69 (34.5 %) male. Primary tumor sites were mainly breast (75; 37.5 %), colorectal (43; 21.5 %), head and neck (24;12.0 %), lung (18; 9.0 %), and gynecological (13; 6.5 %). ECOG was 0 in 70 (35%), 1 in 76 (38 %), 2 in 41 (20.5 %) and 3 in 13 (6.5 %) pts. Out of the 200 cases, 26 (13%) were scored as candidates to BSC. However, while 126 (63%) patients received radio/chemo or hormonal therapy, only 8 (4%) were referred to BSC. From 93 (46.5 %) stage IV pts, 11 (12%) were considered potentially curable by the residents. Conclusions: Medical oncology residents have difficulties identifying BSC candidates among patients with advanced cancer. Development of appropriate skills and application of algorithms to identify BSC pts may be necessary to better control symptoms and avoid unnecessary treatments. No significant financial relationships to disclose.
Endothelial deletion of hypoxia-inducible factor–2α (HIF-2α) alters vascular function and tumor angiogenesis
Authors: Nicolas Skuli, Liping Liu, Anja Runge, Tao Wang, Lijun Yuan, Sunny Patel, Luisa Iruela-Arispe, M. Celeste Simon, Brian Keith
Journal: Blood (2009)
Daily irinotecan and concomitant radiotherapy for locally advanced pancreatic cancer: Feasibility and MTD
Authors: C. Carrie, C. De La Fouchardière, D. Perol, S. Negrier, F. Desseigne, P. Meeus, H. Labrosse, I. Martel Lafay
Journal: Journal of Clinical Oncology (2007)

15124 Background: To determine the maximal tolerated dose (MTD) of daily irinotecan with radiotherapy (RT) in patients (pts) with locally advanced adenocarcinoma of the pancreas. Methods: Between 09/2000 and 05/2006, 30 pts with histologically proved adenocarcinoma of pancreas were included in this prospective phase I/II study. Irinotecan was administrated daily, 1 hour before RT session. Doses were escalated by increment of 2 mg/m 2 every 3 patients for an initial dose of 6 mg/m 2 /day. RT was delivered at 2 Gy per session, 5 fractions per week to a total dose of 50 Gy to the doses tumor volume. Primary endpoint was toxicity; secondary endpoints were tumor objective response (OR) defined as complete or partial response, secondary operability and overall survival (OS). Inoperability was assessed by surgeon. All images were reviewed by a radiologist. OR rates were compared using the Fisher’s exact test. Results: 30 pts were entered over 6 years through 7 dose levels from 6 mg/m 2 /day. Sex ratio was 1:1, median age was 58 years (range 33–71), Karnofsky score was ≥ 90 in 93%. Current median follow-up is 45 months. No dose limiting toxicity was yet observed (last level 18 mg/m 2 /day). Three patients experienced grade 3 toxicity at level 1 (ulcer perforation), level 6 (nausea, vomiting and abdominal pain), and level 7 (nausea, vomiting and hypokaliemia), respectively. OR rates were 33% at 4 weeks. 3/13 pts (23%) included within the 3 first levels (= 10 mg/m 2 /day) experienced an OR at 4 weeks, versus 7/17 (41%) in the levels &gt; 10 mg/m 2 /day (P = 0.44). 3 pts underwent surgery because of control tumor. Median OS was 13 months (95% CI 11–14) with 24 patient’s death. One patient is in complete remission since 21 months. Conclusions: Maximal tolerated dose is not yet reached. Despite response rate is not the main aim of the study, results suggest that RT combined with a higher daily level of irinotecan could be associated with a better tumor control. No significant financial relationships to disclose.
Expression of angiogenic genes in tumor and stroma as biomarkers of prognosis in NSCLC.
Authors: E. Jantus, E. Sanmartin, A. Blasco, R. Sirera, R. Guijarro, T. Donnem, S. Al-Saad, L. Busund, R. M. Bremnes, C. Camps
Journal: Journal of Clinical Oncology (2010)

e21013 Background: In tumor angiogenesis there is a complex interplay between endothelial, stromal, and tumor cells. The VEGF and PDGF families of ligands and receptors play important roles in this process. We investigate the correlations between the expression of ligands and receptors of both families in tumor and stromal cells in patients with resectable NSCLC and their possible role as prognostic biomarkers. Methods: Primary tumor tissues (n = 84) from NSCLC patients (I-IIIA) were used in this study. Representative areas of tumor, stroma and normal tissue were carefully selected. RNA was extracted from 2 sampled cores (0.6 mm) and RT-PCR was performed using TaqMan probes. Relative quantification was calculated using actin-β as endogenous control. Results were normalized against a calibrator sample (NCI-H23 cell line). Statistical analysis were considered significant at p < 0.05. Results: Significant differences between tumor and stroma expression were found for VEGFR-1, -3, neuropilin-1 (NRP-1), PDGF-B, PDGFR-α and -β. We observed a statistical association between lower expression of PDGFR-α (in tumor) and relapse. Significant differences between histological groups (squamous [SCC] vs. adenocarcinoma) were found for: PlGF and VEGFR-2 (in tumor) and VEGF-A, VEGFR-2, -3, NRP-1 (in stroma). Survival analyses revealed that patients coexpressing low tumor VEGFR-2 levels and high stromal VEGF-A levels had significantly worse prognosis (p = 0.017). In the SCC subgroup, data show that patients with high stromal PDGF-A and low tumor cell PDGFR-α levels have shorter overall survival (p = 0.019). Conclusions: There are “angiogenic profiles” in tumor and stroma that could be used as prognostic markers in NSCLC and may help in the selection of patients that will better benefit of the antiangiogenic therapies. Results normalized against normal tissue are under study. Supported by ISCIII grant. No significant financial relationships to disclose.
Results of a Prospective Phase II Randomized Study of Deferasirox (Exjade®) to Prevent Iatrogenic Iron Overload in Patients Undertaking Induction/Consolidation Chemotherapy for Acute Myeloid Leukaemia (HREC/10/QRBW/135)
Authors: Glen A Kennedy, Kirk Morris, Elango Pillai, Cameron Curley, Jason P. Butler, Simon Durrant
Journal: Blood (2012)
1-acyl-sn-glycero-3-phosphocholine Levels are Related to Obesity and Several Markers of Subclinical CV Disease and its Biosynthesis is Associated With Genetic Variants in the 9p21 Region
Authors: Andrea Ganna, Tove Fall, Erik Ingelsson, Lars Lind
Journal: Circulation (2013)

1-acyl-sn-glycero-3-phosphocholine Levels are Related to Obesity and Several Markers of Subclinical CV Disease and its Biosynthesis is Associated With Genetic Variants in the 9p21 Region
“Sebaceous Glands” and “Hyperplasia” Tests as Screening Methods for Tobacco Tar Carcinogenesis
Authors: I Chouroulinkov, P Lazar, C Izard, C Libermann, M Guérin
Journal: JNCI Journal of the National Cancer Institute (1969)

Journal Article “Sebaceous Glands” and “Hyperplasia” Tests as Screening Methods for Tobacco Tar Carcinogenesis Get access Ivan Chouroulinkov, Ivan Chouroulinkov C.N.R.S., Cancer Research Institute, 94 Villejuif, France Search for other works by this author on: Oxford Academic PubMed Google Scholar Philippe Lazar, Philippe Lazar C.N.R.S., Cancer Research Institute, 94 Villejuif, France Search for other works by this author on: Oxford Academic PubMed Google Scholar Camille Izard, Camille Izard C.N.R.S., Cancer Research Institute, 94 Villejuif, France Search for other works by this author on: Oxford Academic PubMed Google Scholar Conrad Libermann, Conrad Libermann C.N.R.S., Cancer Research Institute, 94 Villejuif, France Search for other works by this author on: Oxford Academic PubMed Google Scholar Maurice Guérin Maurice Guérin C.N.R.S., Cancer Research Institute, 94 Villejuif, France Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 42, Issue 6, June 1969, Pages 981–985, https://doi.org/10.1093/jnci/42.6.981 Published: 01 June 1969 Article history Received: 19 December 1968 Accepted: 27 February 1969 Published: 01 June 1969
Quantitative monitoring of circulating epithelial cells for individual therapy control in lung and breast cancer during neoadjuvant treatment, surgery and adjuvant chemotherapy
Authors: K. Pachmann, J. H. Clement, K. Hoeffken, C.-P. Schneider, K. Lobodasch, O. Camara, U. Pachmann
Journal: Journal of Clinical Oncology (2005)

631 Background: A universal characteristic of solid tumors is poor penetration into and distribution of chemotherapeutic agents in the tumor tissue due to interstitial hypertension. Individualized tumor cells shed from the tumors or seeded into the circulation before and at different times of manipulation and therapy may be better accessible and their reduction, therefore, better represent the sensitivity of the tumor. The number of circulating tumor cells can be monitored real-time using the MAINTRAC method and correlated to the extent of manipulation, tumor size reduction in the neoadjuvant and relapse in the adjuvant setting. Methods: Whole blood samples from patients were stained for epithelial cells using fluorochrome-labeled anti human epithelial antibody and positive events quantified using combined laser scanning cytometry and visual verification before each therapy cycle, before and 3, 7 and 14 days after surgery and at different times after completion of therapy. Results: The reduction in number of circulating epithelial antigen positive tumor cells during the first three to four cycles very closely reflected the response of the whole tumor to neoadjuvant therapy (R2= 0.6–0.9). Later massive release of tumor cells from disintegrating tumor tissue occurred into circulation remaining even after surgery which frequently lead to an additional spike of circulating epithelial cells, possibly a mixture of normal and live and dying tumor cells. They were only partly removed during further therapy and cells could be detected in the circulation even after months to years presumably the live tumor cells. Adjuvant therapy reduced the number of circulating epithelial cells. An increase in such cells during or subsequent to therapy was a statistically significant predictor of relapse. Conclusions: Tight monitoring of circulating epithelial/tumor cells from peripheral blood provides so far unexpected insights into the interrelationship between circulation and tumor and may become an important tool for monitoring therapeutic interventions in solid tumors. No significant financial relationships to disclose.
Activity of tivozanib (AV-951) in patients with renal cell carcinoma (RCC): Subgroup analysis from a phase II randomized discontinuation trial (RDT).
Authors: P. Bhargava, B. Esteves, M. Al-Adhami, D. Nosov, O. N. Lipatov, A. A. Lyulko, A. A. Anischenko, R. T. Chacko, D. Doval, W. J. Slichenmyer
Journal: Journal of Clinical Oncology (2010)

4599 Background: Tivozanib, a potent and selective inhibitor of VEGFR-1, 2, and 3 kinases, was tested in a phase II RDT that included patients (pts) with all histologies of RCC, as well as pts who had not undergone nephrectomy or had received prior therapy with cytokines or chemotherapy. The median PFS in all pts was 11.8 months [ASCO 2009; abstract #5032] Methods: A retrospective subgroup analysis was conducted in pts with RCC with clear cell component (CC), pts who had undergone nephrectomy (N), or both (CC+N). Subgroup analysis was also conducted to explore the effect of prior therapy. ORR and PFS were analyzed in pts who attained 25% regression during the first 16 wks, as well as pts who were randomized to placebo and subsequently crossed over to tivozanib after PD on placebo. Results: 272 pts were enrolled between Oct 2007 and July 2008: 83% had RCC with clear cell component, 73% had undergone nephrectomy, and 46% had received prior therapy. Based on a data cutoff of 31 Jan 2009, the ORR by independent radiology review (IRR) was 25.4% in all pts, 27.0% in CC, 28.1% in N, and 29.6% in CC+N. Median PFS was 11.8 mo in all pts, 12 mo in CC, 12 mo in N, and not reached in CC+N. Median PFS was similar in pts who had received prior therapy and those who were treatment naïve. The safety profile of tivozanib was similar to that reported previously, with hypertension (54.4%) and dysphonia (21%) as the most frequent treatment related adverse events (AEs) of any grade. There was a low incidence of fatigue (9.9%), diarrhea (10.7%), stomatitis (3.7%) and hand- foot syndrome (3.3%). With a median duration of treatment of 7.6 mo (range 0.02-15.4 mo), 8.5% pts required dose reduction and 2.9% required treatment interruption due to AEs. Conclusions: Pts with RCC with a clear cell component who have undergone nephrectomy appear to experience the greatest benefit from tivozanib with a median PFS that was not reached at the time of this analysis (based on IRR). Updated ORR and PFS results will be presented. The AE profile of tivozanib was consistent with that of a selective VEGFR inhibitor with minimal off-target toxicities. Tivozanib is currently being tested in a phase III trial in RCC. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration AVEO AVEO
Phase II study of postoperative chemoradiotherapy for esophageal carcinoma
Authors: S. Wu, X. Deng, P. Zhang, C. Xie, X. Zhang, Z. Jin
Journal: Journal of Clinical Oncology (2009)

e15606 Background: Esophageal squamous cell carcinoma is still a virulent disease diagnosed at late stage and remains a major cause of carcinoma mortality in China. The preoperative chemoradiotherapy had been applied to patients with esophageal carcinoma in an effort to reduce the relapse and improve survival. However, randomized controlled trails have shown conflicting results. Intergroup study 0116 demonstrated that postoperative chemoradiotherapy significantly improved overall survival in gastric carcinoma patients. The question remains whether postoperative chemoradiotherapy can improve overall survival in patients with esophageal carcinoma. Our planning study was to investigate the role of postoperative chemoradiotherapy in the multimodality treatment for locally advanced esophageal carcinoma. Methods: From October 2000 to October 2007, Fifty-two patients who underwent esophagectomy with stage II-III esophageal carcinoma were enrolled. All patients received 50Gy of postoperative radiotherapy over 25 fractions in 5 weeks. Two cycles of chemotherapy (Paclitaxel 135mg/m 2 d1,cisplatin 20mg/m 2 d1–3) were administered concurrently on days 1–3 and days 29–31 of radiotherapy. Results: Of the total 52 patients, 28 (54%) developed grade 3 or 4 toxicity.At the time of analysis, 23 patients died. The median follow-up for surviving patients was 23.5 months. The median survival time was 37.2 months. Incidences of tumor recurrence were 53.8 % (28/52) of patients. As expected, distant metastasis was predominant. The 2-year local-regional control survival, distant metastasis-free survival and relapse-free survival were 60.01%, 71.38% and 42.01%, respectively. 1-year and 3-year overall survival were 82.19% and 47.13%, respectively. Conclusions: This novel postoperative chemoradiation regimen for treatment of patients with stage II-III esophageal cancer has a tolerable toxicity and promising 3-year overall survival. No significant financial relationships to disclose.
Nuclear Factor-κB(NF-κB)/Interleukin-6 (IL-6) pathway activation confers resistance to docetaxel (D) in hormone-independent prostate cancer (HIPC)
Authors: J. Domingo-Domenech, A. Rovira, J. Codony-Servat, X. Filella, C. Montagut, J. S. Ross, M. Rolfe, P. Gascon, J. Albanell, B. Mellado
Journal: Journal of Clinical Oncology (2005)

9630 Background: The activation of the NF-κB/IL-6 pathway is associated with androgen-independent progression of prostate cancer (PC) and may be implicated in resistance to chemotherapy. We investigated the role of NF-κB/IL-6 in the response to D in human PC cell lines and in HIPC pts, and the inhibition of NF-κB as a strategy to increase chemosensitivity in PC cells. Methods: The hormone-dependent (LNCaP) and hormone-independent (PC-3, DU-145) PC cells were treated with D+/- PS-1145 (specific IκB kinase 2 inhibitor). Cells were tested for activated p65/ NF-κB (western blot using anti-p65NLS antibody), IL-6 in culture medium (ELISA) and cell viability (MTT). Pts with metastatic HIPC receiving D were tested for plasma IL-6 (ELISA) before the start and every 3–4 weeks until the end of D. Results: In vitro sensitivity towards D was lower for p65NLS expressing and IL-6 producing cells (PC3, DU145) versus LNCaP, with lower p65NLS and no IL-6 production. Media IL-6 increased in both PC-3 and DU-145 after D treatment. Combined therapy with D+PS-1145 resulted in an increased cell death and lower IL-6 production in PC3 and DU145, compared with D alone. We also studied whether plasma IL-6 predicted response to D in 30 HIPC patients. Median age was 67 (range 54–79). Median follow-up:13.2 months (range, 1.5–27.8). Sixteen pts (53.3%) had a PSA-response. Median pre-treatment IL-6 levels were 16 pg/ml (range 0–70) and correlated to PSA- response (median IL-6 was 13.0 pg/ml ± SD 14 in PSA-responder pts vs 33.4 pg/ml ± SD 21.2 in the non-responders, p=0.006). Median PFS was 3.7 months (5.7 vs 1.9 months in pts with IL-6 < and ≥16 pg/ml, respectively, p=0.0001). On multivariate analysis, PS (p=0.05) and pre-treatment IL-6 (p=0.001) were independent prognostic factors for PFS. Conclusion: IL-6 is associated with resistance to D in PC cells and HIPC pts. Moreover, IL-6 is an independent prognostic factor for PFS in these pts. In vitro inhibition of NF-κB by PS-1145 results in a decreased IL-6 production and in an increased cell death when is combined with D. These results suggest that NF-κB/IL-6 pathway inhibition may be a strategy to overcome resistance to D in HIPC. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Millenium Millenium Millenium