tbuckley/cabot-search huggingface dataset:
Gemcitabine in combination with capecitabine in metastatic breast carcinoma: A phase I-II study
Authors: P. G. Giannessi, F. Martella, R. Di Marsico, L. Coltelli, V. Safina, M. Andreuccetti, A. Falcone
Journal: Journal of Clinical Oncology (2005)

870 Background: Gemcitabine (G) and Capecitabine (C) are both actives in metastatic breast cancer (MBC). Methods: To define the maximum tolerated dose of this combination we designed a phase I study with escalating dose of G (from 750 mg/m2 up to 1500 mg/m2 with increments of 250 mg/m2) at day 1 and 8 every 3 weeks combined with C 2000 mg/m2/die on days 1 to 14. To better investigate the activity and toxicity at the recommended doses, a phase II study has been subsequently performed in patients (pts) pre-treated with anthracyclines and taxanes. Results: 12 pts have been enrolled in the phase I study. Dose escalation of G reached the maximum dose planned without observing dose-limiting toxicities. In fact, only 6 pts experienced a grade 2 (WHO) toxicity (anaemia, neutropenia, N/V, mucositis). So far, 21 pts have received G at the recommended dose of 1500 mg/m2 and C 2000 mg/m2/die for a total of 125 cycles with a median of 6 cycles for pt (range1–12). Main characteristics included: median age 51 (range 35–71), median PS 1 (range 0–2) and median sites of metastasis 2 (range 1–4) (14 pts liver, 9 lung, 12 skin/lymphnodes and 14 bone). No G3–4 non-haematological toxicities have been observed except for a G3 dermatitis in one pt. G2 toxicities are diarrhoea, nausea/vomiting and mucositis in 2.4%, 4.8% and 1.6% of cycles, respectively. A reduced dose of G (75% of total dose) was administered at day 8 in 4.8% of cycles because of G3 neutropenia. A G2 neutropenia was observed in 11% of cycles. So far 22 pts are evaluable for response (12 pts in the phase I and 10 in the phase II): 9 pts (41%) obtained an OR (5 CR and 4 PR), 12 (55%) a SD and 1 (4%) progressed. Median duration of response is 5+ months (range 2–13) and median progression-free survival is 7+ months (range 2–16). Conclusion: The combination we used shows a favourable toxicity profile and promising activity in pre-treated MBC. Accrual is continuing to include 39 pts in the phase II study.(Partially supported by Fondazione ARCO) No significant financial relationships to disclose.
RRM1 and BRCA1 mRNA expression levels and clinical outcome of advanced NSCLC patients treated with cisplatin-based chemotherapy
Authors: C. Zhou, S. Zhou, L. Zhang
Journal: Journal of Clinical Oncology (2009)

8097 Background: Platinum-based chemotherapy is the standard treatment for advanced NSCLC patients. RRM1 and BRCA1 are important regulators of chemosensitivity of NSCLC. Methods: Stage IIIb/IV NSCLC patients were given cisplatin-based chemotherapy based upon expression levels of RRM1 and BRCA1 mRNA in the tumor. Expression levels of the two genes were determined by real-time PCR and cut-off points were reported in our previous study. The patients with low expression of RRM1 were treated with gemcitabine/cisplatin up to 4 cycles. The others were treated with vinorelbine or paclitaxel plus cisplatin up to 4 cycles. After the chemotherapy, the patients were followed every 6 weeks up to disease progression and then every 3 months up to death. Results: 90 chemonaive, stage IIIB/IV, PS 0–1 NSCLC patients were enrolled. Age 60 (40–78) yrs old, male/female: 73/27%; adenocarcinoma/squamous/adeno-squamous/undefined NSCLC: 49/33/11/7%;,stage IIIb/IV: 13/87%. Overall response rate was 41.1%, stable disease 42.2%, progressive disease 16.7%. Disease was not progressive in 33 patients. Median TTP was 5 months. Response rate and TTP were better in those with low RRM1 expression ( Table ). Toxicity of the chemotherapy was acceptable. Overall survival will be reported in the conference. Conclusions: RRM1 and BRCA1 mRNA expression levels in non-small cell lung cancer are associated with clinical outcome to cisplatin-based chemotherapy. Prospective studies are ongoing to evaluate the role of the two genes in tailoring chemotherapy in our center. [Table: see text] No significant financial relationships to disclose.
A naturally occurring mutation near the amino terminus of αIIb defines a new region involved in ligand binding to αIIbβ3
Authors: Ramesh B. Basani, Deborah L. French, Gaston Vilaire, Deborah L. Brown, Fangping Chen, Barry S. Coller, Jerry M. Derrick, T. Kent Gartner, Joel S. Bennett, Mortimer Poncz
Journal: Blood (2000)
Prospective change in 25-OH vitamin D levels over long-term follow-up and health outcomes in breast cancer survivors.
Authors: S. K. Taylor, M. Ennis, N. S. Hood, M. Graham, K. I. Pritchard, P. J. Goodwin
Journal: Journal of Clinical Oncology (2010)

6111 Background: 25 OH vitamin D (VitD) deficiency, common at breast cancer (BC) diagnosis, is associated with poor BC outcomes. Change in VitD after diagnosis of BC and associations with other health outcomes are unknown. Methods: 535 patients with T1-3,N0-1,M0 newly diagnosed BC enrolled in a prospective cohort study (1989-1996) were candidates for a long-term follow-up (LTFU) study (2004-2007). 123 had died, 75 were ineligible (33 distant recurrence, 28 other invasive cancer, 14 moved > 1 hour away). Of the remaining 337, 29 (9%) refused participation, 23 (7%) could not be contacted, 285 were enrolled. Women reported medical status, diet and exercise, allowed anthropometric measurements, and completed questionnaires (EORTC QLQ C-30, SF36, POMS, Key Everyday Problems, and Ladder of Life). Fasting blood was analyzed for VitD (nmol/L) by radioimmunoassay (DIASORIN, Stillwater, MN). Associations of VitD with health outcomes were examined in 231 women with VitD levels at baseline and LTFU using standard statistical tests. Results: Reflecting known prognostic effects, LTFU survivors had less aggressive tumors (lower T,N, and grade), lower BMI, and higher baseline VitD than the full cohort. Mean ages at diagnosis and LTFU of the 231 patients were 49.8 ± 8.9 and 62.2 ± 8.5 years respectively. VitD (proportion with adequate levels) increased from 61.3 ± 23.6 (27%) at baseline to 93.8 ± 32.3 at LTFU (71%) (p < 0.0001). Vitamin supplement use also increased. VitD increased more in those reporting (vs. not reporting) osteoporosis at LTFU (46.9 ± 45.2 vs. 28.9 ± 29.0, p = 0.001). Lower VitD at both baseline and LTFU was significantly associated with LTFU cardiovascular risk factors (mainly hypercholesterolemia), but not with cardiac or kidney disease, diabetes, arthritis, asthma, Charlson comorbidity index, QOL, anthropometric measures, or self-reported physical activity; these findings persisted when adjusted for age. Conclusions: VitD increased over time in BC survivors, notably in those with osteoporosis (likely reflecting treatment effects). Lower VitD at diagnosis and LTFU was associated with cardiovascular risk factors but not cardiovascular disease, and did not predict other health outcomes or QOL. No significant financial relationships to disclose.
HEALTH-RELATED QUALITY OF LIFE (HRQOL) ANALYSES IN THE AVAGLIO STUDY, A RANDOMIZED, PLACEBO-CONTROLLED PHASE III TRIAL OF BEVACIZUMAB, TEMOZOLOMIDE AND RADIOTHERAPY IN NEWLY DIAGNOSED GLIOBLASTOMA
Authors: Martin J. B. Taphoorn, Roger Henriksson, Andrew Bottomley, Timothy Cloughesy, Wolfgang Wick, Warren Mason, Frank Saran, Ryo Nishikawa, Arliene Ravelo, Magalie Hilton, Olivier L. Chinot
Journal: Neuro-Oncology (2013)

HEALTH-RELATED QUALITY OF LIFE (HRQOL) ANALYSES IN THE AVAGLIO STUDY, A RANDOMIZED, PLACEBO-CONTROLLED PHASE III TRIAL OF BEVACIZUMAB, TEMOZOLOMIDE AND RADIOTHERAPY IN NEWLY DIAGNOSED GLIOBLASTOMA
Abstract 15328: Acute and Chronic Effects of Percutaneous Renal Sympathetic Denervation on Renal Hemodynamics Using a Novel Catheter for Radiofrequency Ablation: Data from an Animal Study
Authors: Costas Tsioufis, Vasilios Papademetriou, Kyriakos Dimitriadis, Dimitris Tsiachris, Costas Thomopoulos, Euljoon Park, Cary Hata, Christodoulos Stefanadis
Journal: Circulation (2012)

Introduction: Sympathetic overdrive impairs renal blood flow, whereas the effect of renal sympathetic denervation (RSD) on acute and chronic autoregulation of renal hemodynamics has yet to be adequ...
Association of cytokines with quality of life among breast cancer survivors: A randomized pilot study exploring the effect of Tai Chi Chuan
Authors: T. V. Darling, K. M. Mustian, C. E. Heckler, L. J. Peppone, M. C. Janelsins, G. R. Morrow
Journal: Journal of Clinical Oncology (2009)

e20556 Background: While advances in cancer treatment can increase breast cancer (BC) survival, cancer treatment side effects can decrease quality of life (QOL). Cancer cardiotoxicity is a major side effect of chemotherapy and radiotherapy that leads to cardiovascular disease (CVD). The combined burden of cancer and cancer cardiotoxicity drastically affects QOL. Cytokine-mediated inflammatory profiles are dysregulated by cancer treatments and are implicated in the pathogenesis of CVD. Tai Chi Chuan (TCC), an exercise mode with an energy expenditure equivalent to brisk walking, has been shown to improve cardiovascular function and QOL among BC survivors. The purpose of this pilot study was to explore how TCC affects cytokines and how cytokine changes are related to QOL changes among BC survivors. Methods: This pilot study compared the effects of 12 weeks (3, 60 min. sessions/week) of TCC with support therapy on IL-2 and IL-8 and on QOL among 21 BC survivors (mean age=51; range 33–78). Cytokine responses were obtained via serum ELISA and QOL were assessed via the FACIT measurement system pre- and post-intervention. Results: Mean levels of IL-2 decreased in the TCC group (CS=-8.82) but increased in the control group (CS=4.60). Mean levels of IL-8 increased in the TCC group (CS=0.32) but decreased in the control group (CS=-3.82). ANCOVA, controlling for baseline, revealed no treatment effect for IL-2 but there was a statistical trend suggesting a possible treatment effect and baseline interaction for IL-8 (p=0.1). Bivariate analyses revealed a negative association between overall QOL and IL-8 (p=0.07), functional QOL (e.g. ability to work) and IL-8 (p=0.03), as well as physical QOL (e.g. energy level) and IL-8 (p=0.01) in the TCC group. Correlations also showed a negative association between overall QOL and IL-2 (p=0.05) and between functional QOL and IL-2 (p=0.005) among the control group. Conclusions: These findings suggest that TCC-induced changes in cytokines may be associated with changes in QOL, specifically in the physical and functional domains. Future research is needed to verify these pilot study findings and should focus on cardiotoxic effects associated with physical and functional QOL. NCI grant 1R25-CA102618 and Sally Schindel Cone. No significant financial relationships to disclose.
Role of MSI and DCC status to predict response to FOLFOX in metastatic colorectal cancer
Authors: M. Bennamoun, O. Schischmanoff, A. Martin, P. Mariani, L. Ah Koon, J. Morere, G. Des Guetz
Journal: Journal of Clinical Oncology (2007)

21056 Background: Microsatellite instability (MSI) and lack of Deleted Colon Cancer (DCC) protein expression have been observed respectively in ∼15% and 70% of colon cancer cases and are considered as prognostic factors in colorectal cancer (CRC). In adjuvant setting these markers could be considered to decide treatment. We know that MSI colon cancer do not benefit from 5Fluorouracyl (5FU)-based chemotherapy. A current treatment of reference for colon cancer is a combination of 5FU and Oxaliplatin (FOLFOX). Our aim was to determine whether MSI status or DCC expression are predictive markers of FOLFOX efficiency in patients with metastatic CRC. Methods: Tumour specimens were collected from patients with metastatic colon cancer treated with FOLFOX. The FOLFOX regimen was evaluated in first line treatment according to the WHO criteria. The microsatellite instability status was assessed by measurement of the length of five monomorphic mononucleotide markers. DCC protein expression were evaluated by immunohistochemistry. Results: Forty patients (22 men, 18 women), median age 63.5 years (27–83) were treated with FOLFOX. Nine patients had tumours exhibiting high microsatellite instability (microsatellite instability group, MSI group) and 31 patients had tumours exhibiting microsatellite stability (microsatellite stable group, MSS group). In MSS group, we observed 11 partial responses (36%) and only two in MSI group (22%) (not significant difference). Both disease free survival and overall survival were not significantly different for MSI and MSS groups. Determination of DCC status is under investigation. Conclusions: There was no significant difference in chemosensitivity to FOLFOX for MSI and MSS metastatic patients. Therefore FOLFOX regimen could be proposed to metastatic patients irrespective of MSI status. The study of the relationship between DCC expression and response to FOLFOX is ongoing. No significant financial relationships to disclose.
Angiogenesis inhibition in metastatic hormone refractory prostate cancer (HRPC): A randomized phase II trial of two doses of the matrix metalloproteinase inhibitor (MMPI) BMS-275291
Authors: P. N. Lara, J. Longmate, W. Stadler, D. I. Quinn, P. Twardowski, C. I. Martel, N. J. Vogelzang, E. E. Vokes, J. H. Doroshow, D. R. Gandara
Journal: Journal of Clinical Oncology (2004)

4647 Background: BMS-275291 is a selective MMPI that does not inhibit sheddases implicated in the dose-limiting arthritis of older MMPIs. We conducted a randomized phase II trial of 2 doses of BMS-275291 (1200 vs. 2400 mg) in HRPC patients (pts) with bone metastasis to probe for a dose-response relationship and assess differential toxicities. Methods: Primary endpoint was 4-month progression-free survival (PFS): 68 pts were needed to detect PFS > 50% versus a null hypothesis of PFS 60%, and no more than 1 prior chemotherapy regimen. Pts were randomized to 1200 mg po QD (Arm A) vs. 1200 po BID (Arm B). Results: Rapid multi-center accrual resulted in 80 pts randomized w/in 14 months (mos): Arm A –39, Arm B –41. Pt characteristics: median age=70 yrs; Gleason's 7/unspecified = 0/34/33/13; KPS > 80% = 67 pts; prior chemo = 25%. Attributable grade 3–4 toxicities were 15% in Arm A, 24% in Arm B. There were no responders. At 2 mos, 22 progressed on Arm A vs. 29 on B. PFS at 4 mos in Arms A and B were 25% and 8%, respectively. Median overall survival was not reached in Arm A, 12 mos in Arm B. PSA slope was compared in 54 pts with at least 2 pre-treatment, on-study, and post-treatment PSA values using a paired t-test. Mean pre/post change in PSA slopes was 0.0018 (p=0.3), equivalent to an increase in PSA doubling time from 70 to 86 days. Evaluation of bone metabolism markers from serial plasma/urine samples is ongoing. Conclusions: 1) BMS-275291 was well tolerated in HRPC pts and had no dose limiting arthritis. 2) Toxicities differed modestly according to dose-schedule employed. 3) PFS and response were similar between the arms, with a trend towards decreasing PSA slope pre- vs. on-treatment. 4) In view of its presumed cytostatic mechanism of action, further studies to define the effect of BMS-275291 in earlier stage disease could be performed at either dose studied here. (NOI CM17101, CM17102, ACS-CRTG 19701-CCE) No significant financial relationships to disclose.
Analysis of circulating tumor cells in prostate, colorectal and ovarian cancer using robotic microscopy
Authors: N. Romas, M. W. Kilpatrick, T. G. Ntouroupi, A. Seppo, Y. Kim, S. Cohen, W. F. Bodmer, P. Tsipouras, T. Tafas
Journal: Journal of Clinical Oncology (2008)

11084 Background: Identification and analysis of rare circulating tumor cells (CTCs) has great clinical potential. The challenge to the utilization of rare tumor cells diagnostically is to accurately detect cells present in small numbers in a large, complex cellular background, whilst preserving cell morphology, such that the cells detected can be fully analysed. Methods: A customized robotic microscopy system, developed specifically for cell identification and analysis, by automated fluorescence microscopy, was used. Fully automated slide analysis allows rare cell detection, avoiding complex purification procedures which risk cell loss and can create unresolved clusters of normal and cancer cells. Blood samples were collected from 7 prostate, 10 colorectal, and 4 ovarian cancer patients and 11 healthy controls. The mononuclear cells were labeled with Cam5.2 directed against epithelial specific Cytokeratins 7/8 and either AUA1 (directed against EpCam) or anti-PSA. For a subset of patients, FISH analysis was further performed. Results: Five out of seven prostate cancer patients presented EpCam/cytokeratin or PSA/cytokeratin-positive cells with the morphological characteristics of tumor cells. The number of cells ranged from 2.2 to 22.7 per ml blood. All the colorectal and ovarian cancer patients had EpCam/cytokeratin-positive cells, with the number of cells ranging from 0.1–18.5 and 0.5–1.9 cells per ml blood, respectively. No immunoreactive cells were detected in the blood samples from healthy volunteers. All samples additionally analysed by FISH showed polysomy of at least one of chromosomes 7 and 8. Conclusions: These data support the potential clinical utility of CTC detection and analysis. By maintaining the integrity of the tumor cells detected, the approach has the added advantage of allowing the further analysis of both cell morphology and genotype. In this way, utilization of different combinations of antibodies and/or a combination of antibodies and genomic FISH probes, could provide valuable information, as an aid to prognosis and treatment of cancer patients, or the monitoring of response to treatment. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration Ikonisys Inc Ikonisys Inc Ikonisys Inc Ikonisys Inc
Development of radiolabeled mapatumumab and imaging in solid tumor patients who are treated with gemcitabine, cisplatin, and mapatumumab
Authors: C. Oldenhuis, E. C. Dijkers, E. W. Duiker, N. L. Fox, J. L. Klein, J. A. Gietema, A. H. Brouwers, M. N. Lub-de Hooge, E. G. de Vries
Journal: Journal of Clinical Oncology (2009)

e14521 Background: Mapatumumab is a fully human agonistic monoclonal antibody (mAb) to the tumor necrosis factor-related apoptosis-inducing ligand receptor 1 (TRAIL-R1). Mapatumumab combined with gemcitabine and cisplatin increased cytotoxicity in preclinical models and was safe in a phase 1 study. To study its biodistribution, 111 Indium ( 111 In) labeled mapatumumab was developed for γ-camera imaging and tested in mice. Subsequently, 111 In-mapatumumab scintigraphy was performed in patients (pts). Methods: Mapatumumab was labeled with 111 In. Labeling efficiency, radiochemical purity, stability and binding properties were determined in vitro. Biodistribution was studied at multiple time points in nude mice bearing human xenografts (SKBR3 or SW948). Tissue activity was expressed as % injected dose/gram tissue (%ID/g). In a feasibility study, gemcitabine 1250 mg/m 2 IV on days 1 and 8, cisplatin 80 mg/m 2 IV and mapatumumab 20 mg/kg on day 1 was administered to advanced solid tumor pts every 21 days. In cycles 1 and 3, pts underwent γ-camera imaging directly, and at day 1, 3, and 6 after 150 MBq 111 In-mapatumumab IV (planar and single-photon emission computed tomography (SPECT)). Results: Labeling efficiency was 92.0% and radiochemical purity 96.0%. 111 In-mapatumumab was stable in serum for 1 week at 37°C and specific TRAIL-R1 binding was maintained after labeling. In mice, high uptake was seen in liver (8.14 ± 0.75 %ID/g), kidneys (16.30 ± 1.75 %ID/g), spleen (7.25 ± 2.64 %ID/g) and bone (5.68 ± 1.31 %ID/g), with a maximum 24–72 hours (h) after tracer injection. Maximum uptake in the xenografts was observed after 72 h (7.55 ± 3.54 %ID/g for SKBR3 and 6.21 ± 2.03 %ID/g for SW948). Five pts have been enrolled in the ongoing clinical study. Known tumor lesions (by CT-scan) showed variable tracer uptake in 3 pts, while within pts not all known tumor lesions were positive on SPECT. Conclusions: Mapatumumab can be efficiently radiolabeled for clinical use. Preliminary results show that mapatumumab scintigraphy identifies some but not all tumor lesions in pts. This is the first demonstration that mAb targeting a TRAIL-R distributes to tumor tissues in patients and could potentially guide mapatumumab therapy. [Table: see text]
High-dose bolus interleukin-2 in elderly patients (&gt;60 years old) with metastatic melanoma or renal cell cancer
Authors: J. Homsi, L. C. Kim, D. Goetz, D. Chen, M. Fishman, A. Daud
Journal: Journal of Clinical Oncology (2007)

19559 Background: Although durable complete responses have been reported from using high-dose bolus interleukin-2 (HDB IL-2) in a small number of patients with metastatic melanoma and renal cell cancer (RCC), IL-2 toxicity limits its use especially in the elderly. Methods: the medical records of patients older than 60 years old with melanoma or renal cell carcinoma who received HDB IL-2 at the Moffitt Cancer Center between 2000–2005 were reviewed. The effect of increased age, primary diagnosis, and the HDB IL-2 regimen used on the side effects, number of administered doses, and survival was analyzed. Results: 55 cycles were administered to 35 patients (23 RCC, 12 melanoma, 26 men). Median age was 67 years old (range: 61–77). 17 patients received a traditional regimen (one cycle: 600,000 IU/Kg intravenously every 8 hours for 14 doses repeated in 2 weeks, maximum of 28 doses) and 18 received a clinical trial regimen (one cycle: 600,000 IU/Kg intravenously every 8 hours for 5 doses repeated weekly, maximum of 20 doses). Median number of administered cycles was 1 (range 1–4) and median number of total doses was 24 (range 3–79). Increased age was not related to total number of administered doses. Median percentage of IL-2 administered in a cycle was 75% of planned (range 11%-100%). Reasons to discontinue therapy were: oliguria (35%), hypotension (25%), and arrhythmia (15%). Side effects in all cycles were: hypotension (71%), oliguria (67%), Arrhythmia (18%), Myocardial infarction (7%), pulmonary edema (7%), hypothyroidism (4%), confusion (4%), seizures (2%) and stroke (2%). Pressors were used in 58% of all cycles. 20 patients died within a year from starting treatment and 5 lived more than 2 years (4 had RCC). Conclusions: 1) HDB IL-2 has multiple and life-threatening side effects in the elderly and caution is needed when selecting these patients to such therapy 2) the number of doses administered is comparable to that general population 3) more studies are needed to identify the population that would mostly benefit from HDB IL2. [Table: see text] No significant financial relationships to disclose.