tbuckley/cabot-search huggingface dataset:
Intraperitoneal cisplatin and whole abdomen hyperthermia for relapsed ovarian carcinoma
Authors: E. L. Jones, L. R. Prosnitz, T. V. Samulski, J. Soper, A. Berchuck, D. Clarke-Pearson, M. W. Dewhirst, Z. Vujaskovic
Journal: Journal of Clinical Oncology (2004)

5038 Background:The study was designed to determine the maximum tolerated dose (MTD) of intraperitoneal cisplatin [CDDP] combined with intravenous thiosulfate and concurrent whole abdomen hyperthermia for advanced, recurrent or progressive ovarian carcinoma. Furthermore, clinical activity, toxicity and feasibility of the treatment regimen were assessed. Methods:Between September 1991 and November of 1998 forty one patients with advanced epithelial ovarian cancer received escalating doses of intraperitoneal cisplatin (6 cycles given every 3–4 weeks) and whole abdomen hyperthermia with intravenous thiosulfate as second line treatment. Thermometry was obtained both intraperitoneally as well as intravaginally and intrarectally. Results:The first three patients started at a dose of 60 mg/m2 of intraperitoneal cisplatin. All patients completed this dose without complication. Nine patients were entered at the 100 mg/m2 dose, nine patients at 140 mg/m2 and twenty patients at 180 mg/m2. Seven patients completed the full six cycles at 180 mg/m2 dose level and this was deemed to be the maximally tolerated dose (MTD). There were two clinical partial responses (PR) at 60 mg/m2, and one pathologic complete response (CR) and two clinical PR at 100 mg/m2. At 140 mg/m2 there was one pathologic CR, one clinical CR, and two clinical PR. At 180 mg/m2 there were three pathologic CR, four clinical CR, and two clinical PR. This was determined both by CA 125 measurements as well as third look laproscopic evaluation. Median survival for all patients from protocol entry was 30 months (range 2 to 107 months). Median duration of complete response for those achieving a pathologic CR was 14 months (range 2 – 27 months), and median survival for those achieving a CR to this regimen was 35 months (range 14 – 71 months, 95% CI 16 – 54 months). Conclusions:Salvage platinum based intraperitoneal cisplatin with hyperthermia did achieve pathologic complete response in selected patients, and the proportion of responders increased with greater cisplatin doses. These promising results suggest a role for the use of adjuvant whole abdomen hyperthermia as a means of augmenting chemosensitization. No significant financial relationships to disclose.
Enhanced endothelialization and microvessel formation in polyester grafts seeded with CD34+ bone marrow cells
Authors: Vishwanath Bhattacharya, Peter A. McSweeney, Qun Shi, Benedetto Bruno, Atsushi Ishida, Richard Nash, Rainer F. Storb, Lester R. Sauvage, William P. Hammond, Moses Hong-De Wu
Journal: Blood (2000)
Phase I dose escalation study to assess tolerability and pharmacokinetics of recombinant human IL-18 (rhIL-18) administered as fourteen daily subcutaneous injections in patients with solid tumors
Authors: N. Lewis, J. Gollob, R. Cohen, M. Thoreson, C. Oei, L. Kirby, K. Koch, L. Thurmond, M. Dar, W. Bell
Journal: Journal of Clinical Oncology (2004)

2591 Background: Tolerability of rhIL-18 (SB485232) administered intravenously on 5 consecutive days was reported previously (Proc. ASCO 22:713a 2003). A subcutaneous (SC) route of administration was evaluated to compare the effects of route of administration on the biological/clinical activity and tolerability of rhIL-18. Methods: In an ongoing phase I dose-escalation study, rhIL-18 was administered as daily subcutaneous injections for 14 consecutive days to patients (pts) with solid tumors. Doses ranging from 3–300 μg/kg/day are planned. The objectives are to determine tolerability, define a biologically effective dose, and assess pharmacokinetics, immunogenicity, immunomodulatory and anti-tumor activity of rhIL-18. Patients with detectable anti-SB-485232 antibodies at screening were excluded. Results: Six pts were treated at dose levels up to10 μg/kg/day. No dose limiting toxicities were observed. Drug-related adverse event data are available for 6 pts: Grade (G) 1 fever (n=1), chills (n=1), arthralgias (n=2), myalgias (n=2), hypotension (n=1), hypertension (n=1), tachycardia (n=2), rash (n=1); G1–2 injection site reaction (n=2); G2 anemia (n=1), lymphopenia (n=1); G1 increased AST (n=1), hyperbilirubinemia (n=1). No treatment-related antibodies to SB-485232 were detected. Plasma rhIL-18 concentrations demonstrated modest accumulation and an absolute bioavailability of approximately 20%. A rapid fall in circulating NK cells within 8 hours of the first SC injection as well as upregulation of FasL and CD69 on NK, CD8+, and CD4+ cells were observed. Conclusions: Preliminary data demonstrate rhIL-18 administered SC for 14 consecutive days is well tolerated at doses up to 10 μg/kg/day. In addition, there is evidence of immunomodulatory activity even at the lowest dose level at time points when no detectable rhIL-18 is present in circulation. Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration GlaxoSmithKline GlaxoSmithKline GlaxoSmithKline
Phase II trial of weekly <i>nab-</i>paclitaxel in combination with bevacizumab as first-line treatment in metastatic breast cancer
Authors: M. A. Danso, J. L. Blum, N. J. Robert, L. Krekow, R. Rotche, D. A. Smith, P. Richards, T. Anderson, D. A. Richards, J. O'Shaughnessy
Journal: Journal of Clinical Oncology (2008)

1075 Background: In a clinical trial of 722 patients (pts) with locally recurrent metastatic breast cancer (MBC) solvent-based paclitaxel 90 mg/m2 was administered intravenously (IV) over 1 hr weekly for 3 weeks followed by a week of rest (q3/4w) alone or in combination with bevacizumab 10 mg/kg every 2 weeks (q2w) (Miller et al, ASCO 2005). As compared with single agent, the combination had a greater median progression-free survival (PFS; 11.4 vs. 6.11, p < 0.0001) and overall response rate (ORR; 30% vs. 14%, p < 0.0001). The purpose of the current study is to evaluate safety and tolerability and PFS, and secondarily ORR, of a solvent-free, 130- nanometer albumin bound (nab-) paclitaxel in combination with bevacizumab in MBC. Methods: In this multicenter, open-label study in the US Oncology Research Network, HER2-negative pts with MBC, receiving first line chemotherapy were given weekly nab- paclitaxel 125 mg/m2 IV infused over 30 minutes on days 1, 8, and 15, and bevacizumab 10 mg/kg on days 1 and 15 of a 28- day cycle. HER2-negative pts with measurable adenocarcinoma of the breast with ECOG PS 0–2 were included. Results: 49 women were enrolled from 19 October 2005 to 26 October 2007 with 41 pts treated (mean age, 59 years; mean # cycles, 4.0). To date 27 pts are evaluable for response. 93% of pts had visceral disease 59% had prior chemotherapy, 41% had anthracycline, 12% had docetaxel and 12% had paclitaxel in the adjuvant setting. The confirmed ORR was 30% (8/27 pts with a partial response). Stable disease>16 wks was 22% (6/27). The median PFS was 9.2 months (95% confidence interval: 5.3 - >16.1). Grade 3, 4 hematologic adverse events were neutropenia (30%, 16%) and anemia (8%, 3%). The most common nonhematologic grade 3, 4 adverse event was sensory neuropathy (10%, 2%). Conclusions: Results on this preliminary analysis shows that nab-paclitaxel in combination with bevacizumab has promising PFS and an acceptable safety profile with no unanticipated toxicities. Updated data will be presented. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration Abraxis Abraxis
Analysis of Thymidine Kinase Activity and Glucocorticoid-Binding Capacity in the Thymuses of Healthy and Tumor-Bearing Chickens
Authors: Anikó Náray, Péter Arányi, István Földes, István Horváth
Journal: JNCI Journal of the National Cancer Institute (1977)

Thymidine kinase activity in the lymphoid organs of healthy and tumor-bearing chickens was studied after hydrocortisone or dexamethasone treatment. Glucocorticoid hormones (10 mg/100 g body wt) administered twice in 48 hours resulted in an 80% decrease in thymidine kinase activity in the thymuses of healthy chickens, whereas birds with transplantable MC 29 chicken hepatoma failed to respond to the hormones. In the bursae of Fabricius of healthy or tumor-bearing chickens, thymidine kinase activity did not change considerably after administration of hydrocortisone or dexamethasone. The steroid-binding capacity in cellfree systems prepared from thymuses of tumor-bearing birds was significantly decreased. Thus the difference in steroid-binding capacity between thymuses of healthy and tumor-bearing chickens correlated well with, and could account for, the failure of hydrocortisone and dexamethasone to reduce the thymidine kinase level in tumor-bearing birds.
Phase I dose-escalation study of sodium stibogluconate (SSG), a protein tyrosine phosphatase inhibitor, combined with interferon-alfa for patients with solid tumors
Authors: A. Naing, J. M. Reuben, C. F. Verschraegen, L. H. Camacho, S. Stephen, D. S. Hong, J. J. Wheler, S. Fu, M. Martinez, L. Akinsanmi, R. Kurzrock
Journal: Journal of Clinical Oncology (2008)

3011 Background: SSG is a potent inhibitor of IFN-α signaling protein tyrosine phosphatases (PTPases). Combination of SSG+IFN alpha-2b inhibits growth of melanoma, myeloma, colon, prostate, and breast carcinoma cell lines in vitro. We designed a dose-finding trial to assess toxicities, MTD, PK, PTPase modulation, and the immune effects of this combination. Methods: A phase I trial testing a 6-week regimen consisting of: (1) IV SSG for 5 days of the first week of cycle (2) IFN α-2b was administered SQ 3 times/wk (tiw) during week (3) Both drugs are given in combination thereafter on a 2 wk-on /1 wk-off schedule. SSG was administered at 5 different dose levels (400; 600; 900; 1,350; 1,125mg/m2). Results: 19 patients (17 patients at MDACC and 2 at UNM) (median patient age =59 yrs, range 33–82) received 31 courses. Diagnoses included; melanoma (5), colorectal (3), pancreas (3), and prostate (1), neuroendocrine (1), adenocystic carcinoma (1), malignant granulosa cell (1), squamous cell carcinoma of head/neck (1), peritoneal mesothelioma (1) and ovarian (1). Common toxicities include fatigue, myalgia, fever, chills, serum elevation of amylase/lipase, leukopenia, and thrombocytopenia. Hypokalemia and rash were dose-limiting toxicities at 1,350 mg/m2. Cmax on Day 8, 30 min post IV administration was (72,428 mcg/L); elimination half-life is 22.5 hours. Significant changes in immune parameters were observed in patients receiving 900 mg of SSG and above. There was a significant decrease in the number of CD4+CD25hi T-regulatory cells (26.6/μL vs 14.0/μL, p = 0.012) and in myeloid DC (3.1/μL vs 1.7/μL, p = 0.028). With respect to function, there was significant increase in %NKC that synthesized perforin (65.9% vs 75.6%, p = 0.046), and an increase in the % plasmacytoid DC that secreted IFN-α (3.2% vs 19.8%, p = 0.018) in response to activation through TLR7/8 by CL097. Conclusions: SSG in combination with IFN was well tolerated. Dose escalation stopped at 1,350 mg/m2. PK data suggest a linear accumulation of SSG with rapid excretion after 120 minutes. Preliminary immune monitoring suggests that the combination of SSG and IFN-α is capable of augmenting cellular immunity. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration Pharmion Pharmion, VioQuest Pharmion, Vioquest
Old, white, rich patients find it easier to get GP appointments than young, poor, black patients
Authors: Gareth Iacobucci
Journal: BMJ (2015)

Patients in England from a white ethnic background and those from affluent areas find it easier to get an appointment with their family doctor than those from other ethnic groups or deprived areas, a new report from the National Audit Office (NAO) has found.1

The report also found that older patients were more likely than younger patients to get an appointment and more likely to rate the appointment as convenient.

Overall, auditors found that people’s experience of accessing general practice appointments remained largely positive, with 89% of patients in 2014-15 reporting that they could get an appointment when they had last tried to book one.

But despite this the NAO noted that patients’ satisfaction with access to their GP was slowly declining, with a fifth of patients reporting …
Effect of Various Levels of Dietary Butylated Hydroxyanisole on Methylazoxymethanol Acetate-Induced Colon Carcinogenesis in CF1 Mice&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;&lt;xref ref-type="fn" rid="FN3"&gt;3&lt;/xref&gt;
Authors: Bandaru S. Reddy, Yosiichi Maeura, John H. Weisburger
Journal: JNCI Journal of the National Cancer Institute (1983)

The effect of dietary butylated hydroxyanisole (BHA) on methylazoxymethanol (MAM) acetate-induced colon carcinogenesis was studied in female CF1 mice fed the NlH-07 open formula diet and the AIN-76 semi purified diet. BHA levels in the experimental diets were 0.6% in the AIN-76 diet and 0.03, 0.1, 0.3, and 0.6% in the NlH-07 diet. Starting at 5 weeks of age, groups of mice were fed diets with or without BHA. At 7 weeks of age, all animals except vehicle-treated controls were given ip injections of MAM acetate (15 mg/kg body wt), four times in 11 days (low dose) and eight times in 22 days (high dose). Animals were fed their experimental diets until 2 weeks after carcinogen treatment, when those receiving the BHA diets were fed their respective control diets without BHA until termination of the experiment. With a low dose of carcinogen, BHA in the NIH-07 diet inhibited lung tumor incidences in a dose-related manner; with a high dose of carcinogen the inhibition was apparent with 0.1–0.6% BHA. Lung tumor incidence was lower in the low carCinogen treated group fed the AIN-76 diet containing 0.6% BHA than in the animals fed the diet without BHA. Colon tumor incidence was lower in mice fed the NIH-07 diet containing 0.3 and 0.6% BHA and treated with a low dose of carcinogen than in the animals fed no BHA; colon tumor multiplicity (adenomas/animal and adenomas/tumor-bearing animal) was inhibited in mice fed the diets containing 0.03–0.6% BHA. In groups given a high dose of MAM acetate, the NlH-07 diet with 0.03–0.6% BHA and the AIN-76 diet with 0.6% BHA greatly inhibited colon tumor incidence and multiplicity.
Abstract 12432: A Novel Vasculoprotective Role of Nitric Oxide Synthases in Bone Marrow-Derived Vascular Progenitor Cells
Authors: Masato Tsutsui, Yumi Furuno, Tsuyoshi Morishita, Nobuyuki Yanagihara, Masahito Tamura, Hiroaki Shimokawa, Yutaka Otsuji
Journal: Circulation (2013)
Docetaxel: current status and future prospects.
Authors: E Eisenhauer
Journal: Journal of Clinical Oncology (1995)

Article Tools Article Tools OPTIONS & TOOLS Export Citation Track Citation Add To Favorites Rights & Permissions COMPANION ARTICLES No companion articles ARTICLE CITATION DOI: 10.1200/JCO.1995.13.12.2865 Journal of Clinical Oncology - published online before print September 21, 2016 PMID: 8523048 Docetaxel: current status and future prospects. E EisenhauerxE EisenhauerSearch for articles by this author https://doi.org/10.1200/JCO.1995.13.12.2865 First Page PDF © 1995 by American Society of Clinical Oncology
Phase I trial of N-methylformamide (NMF, NSC 3051).
Authors: P J O'Dwyer, M Donehower, L M Sigman, C L Fortner, J Aisner, D A Van Echo
Journal: Journal of Clinical Oncology (1985)

N-methylformamide (NMF) is a polar-planar solvent with both cytotoxic and differentiating activity in preclinical models; it also acts as a radiosensitizer. We treated 17 patients with 18 courses of NMF on a schedule of six weekly doses, administered on a rapid intravenous infusion, which were escalated from 875 to 2,000 mg/m2/wk. The predominant toxicity was a dose-related syndrome of fatigue, malaise, nausea, and anorexia, which was reflected by a decrease in performance status (Karnofsky) of greater than or equal to 20% in six of ten patients who received doses greater than or equal to 1,500 mg/m2/wk. Other gastrointestinal toxicities included moderate vomiting and mild diarrhea. Reversible increase of liver enzymes occurred in six of ten patients at doses greater than or equal to 1,500 mg/m2/wk. The maximum tolerated dose on this schedule is 1,500 mg/m2/wk; the dose recommended for phase II studies is 1,125 mg/m2/wk. Future studies of this regimen in a combined modality setting are planned.
Evaluation of angiogenis activation during interleukin-2 infusion in patients with renal cell cancer (RCC)
Authors: C. Simonelli, R. Talamini, A. Bearz, M. Berretta, P. Monini, C. Sgadari, I. Sartor, B. Ensoli, E. Vaccher, U. Tirelli
Journal: Journal of Clinical Oncology (2006)

14640 It is well known that during IL-2 administration a complex activation of the cytokine network is on going, but few data are available about the effect of this activation on angiogenesis. In our Institution all patients with metastatic RCC undergo to the following schedule of IL-2 infusion: IL-2 10 MIU continuous infusion (ci) 5/7 days, one week off followed by IL-2 10 MIU ci 5/7 days, 4 week off (1 cycle); for a total number of 2 cycles. We evaluated the activation of angiogenesis measuring the plasma level of VEGF MMP2 and MMP9 before, during and after the 5 days IL-2 ci. In 13 patients analysed, before IL-2 ci, we have the following median level of plasma VEGF (773+ 378 pg/ml), MMP2 (55.9 + 19.9 ng/ml) and MMP9 (1146+498 ng/ml). The baseline median values of VEGF MMP-9 showed a trend to correlate with the number of metastasis before therapy. During 3 days of IL-2 ci we did not observed any significant increase of VEGF MMP2 and MMP9 as well as after 24 hours from the end of the 5 days ci. On the contrary, at the same time-points, during and after IL-2 ci, we observed the activation of pro-inflammatory cytokines network, measured by the statistically significant increased levels of neopterin IFN-γ and TNF-α and sIcam.This preliminary observation demonstrated that IL-2 ci, even if it highly activates the release of pro-inflammatory factors, does not affect the release of angiogenic surrogate markers such as VEGF MMP2 and MMP9. On the basis of our experience we can suggest that the most suitable time to test angiogenesis inhibitors during IL-2 therapy appear to be the intervals between IL-2 administration and not during IL-2 infusion when the most severe side effects occur and it is not observed a significant increase of angiogenic factor release. No significant financial relationships to disclose.
Interaction of sunitinib and paclitaxel on inhibition of human angiosarcomas
Authors: M. K. Wong, D. O. Henry, C. K. Mavis, S. Chen, P. R. Reczek
Journal: Journal of Clinical Oncology (2008)

14629 Background: Angiosarcoma (AS) is a malignancy of vascular endothelial cells. AS respond to cytotoxic chemotherapy and in particular taxanes such as paclitaxel. However tumor resistance is a major cause of treatment failure. In order to study this, we successfully established primary cell lines derived from patients with AS. The resistance phenotype in these cells is associated with Vascular Endothelial Growth Factor (VEGF) overexpression and interference of this pathway can have beneficial therapeutic consequences. Thus we hypothesized that human AS would be particularly sensitive to the combination of the VEFGR inhibitor, sunitinib, plus the cytotoxic agent, paclitaxel. Methods: Primary cell lines from a patient with sporadic breast angiosarcoma were used for this study. AS cells were tested in vitro with various concentrations of paclitaxel (0 -20 ng/ml) and sunitinib (0 - 10 uM) either individually or again in combination. Human AS tumors were established in nu/nu mice and treatment with test agent began when tumors were 100 m3 in size. Paclitaxel was given once by intraperitoneal injection. Sunitinib was given as a daily oral dose. Results: Human AS cells are maximally inhibited in vitro by paclitaxel at 5 ng/ml and by sunitinib at 10 uM. Paclitaxel 1 ng/ml or sunitinib 2.5 uM individually has minimal effect on AS cells however there was significant inhibition when cells were treated with both drugs at this dose level. The combination of both drugs is more potent than each drug by itself at all doses tested. This also held true in vivo. The addition of oral sunitinib to paclitaxel 7.5 mg/kg or 21 mg/kg significantly inhibited tumor growth over those mice treated with paclitaxel alone. There was gross inhibition of angiogenesis in the paclitaxel and sunitinib groups; however the most profound inhibition was in the combined treatment group. Conclusions: The combination of sunitinib and paclitaxel is effective against human angiosarcoma cells. In vivo inhibition may act through enhanced anti-tumor angiogenesis. No significant financial relationships to disclose.
Using patient-reported outcomes for technology assessment (TA) and quality improvement (QI) in prostate cancer brachytherapy
Authors: R. C. Chen, A. L. Zietman, A. V. D’Amico, I. Kaplan, J. A. Clark, J. Manola, J. A. Talcott
Journal: Journal of Clinical Oncology (2007)

5139 Background: Despite their sensitivity, validity and increasing prominence in clinical reports, patient-reported outcomes have played little role in TA and QI. We used our validated disease-specific instrument to compare outcomes after alternative brachytherapy techniques for early prostate cancer, both experimental vs. standard technique and between implementations of the standard technique. Methods: One radiation oncologist performed experimental MRI-guided brachytherapy (MRB) on protocol and 2 performed standard ultrasound-guided brachytherapy (USB1 and USB2). We prospectively measured urinary and bowel function of 237 men before brachytherapy and at 1, 3 and 12 months after treatment. Each symptom index is scored from 0 (no dysfunction) to 100 (maximum dysfunction). We report outcomes both as mean change in scale score from baseline and as the distribution of functional categories, grouped by pretreatment functional level: normal, intermediate, and poor (severe dysfunction). Results: Among all patients, MRB caused less urinary obstruction/irritation at 3 months after treatment than ultrasound-guided brachytherapy (mean score change 9.2 vs. 23.6, p&lt;.001). Significant differences in outcome also existed between USB1 and USB2 (19.5 vs. 29.0, p=.01). When baseline function was normal, 15% of MRB patients reported severe 3-month dysfunction, compared to 50% of USB1 and 71% of USB2 patients ( Table ). Outcomes of patients with pretreatment urinary dysfunction differed less. Preliminary results documenting inferior outcomes prompted modification of the USB2 brachytherapy technique, producing a trend toward improved outcomes in small patient numbers (mean score change: 30.4 vs. 22.8, p=.25). Bowel symptom outcomes varied less. Conclusions: Patient-reported outcomes can provide sensitive and valid indicators of TA and QI that may contribute to optimal patient-centered care. [Table: see text] No significant financial relationships to disclose.