tbuckley/cabot-search huggingface dataset:
Socio-demographic variables influence outcome in Radiation Therapy Oncology Group head and neck trials
Authors: A. A. Konski, T. Pajak, B. Movsas, J. Coyne, J. Harris, C. Gwede, A. Garden, S. Spencer, C. Jones, D. Watkins-Bruner
Journal: Journal of Clinical Oncology (2004)

6043 Background: The specific aim of this study was to evaluate the influence of socio-demographic factors on local-regional (LR) control and survival of patients treated on RTOG head and neck cancer clinical trials. Methods:Patients treated on RTOG 9003, RTOG 9111 and RTOG 9703 were utilized. The model was stratified by protocol and a step-up procedure using a 0.05 significance level was initially used to build the model. The Cox proportional hazards model was used to determine if any tumor or socio-demographic variables (age, gender, race, Karnofsky Performance Status (KPS), T-stage, N-stage, marital status, number of persons in household, education level, household income prior to cancer diagnosis, and tobacco use) are independent prognostic variables for LR control and/or survival. Results:A total of 1901 patients were entered onto the 3 RTOG trials of which 1822 were analyzable. Fifty-nine percent of the analyzable patients were from 9003, 28% from 9111 and 13% from 9703. In multivariate analyses T and N-Stage, and KPS were significant for both survival and LR control. Variables found to have prognostic value independent of disease related variables were gender, age, marital status and income for survival and marital status and race for LR control. A significant interaction between marital status and gender existed for both endpoints. Male patients currently married or a live-in partner, did significantly better than the other male patients, while no such effect was seen in the female patients. Tobacco use at protocol entry was evaluated in the multivariate model with only RTOG 9003 and 9111, and was significant for both endpoints. Conclusions: The socio-demographic variables race and marital status were found to have independent prognostic value for predicting LR control. Income and marital status were found to have independent prognostic value for predicting survival. These variables may identify patients requiring additional support and early interventions during the course of treatment to improve outcome. No significant financial relationships to disclose.
Comparison between immature and mature dendritic cells in a vaccination trial
Authors: R. Ridolfi, A. Riccobon, M. Petrini, L. Ridolfi, L. Fiammenghi, M. Stefanelli, M. Selva, D. Amadori
Journal: Journal of Clinical Oncology (2004)

2562 Background: Dendritic cells may be responsible for awakening immunocompetence in cancer patients (pts). They can be administered therapeutically after loading with tumor antigens (immature dendritic cells, iDC), when it is hypothesized that they migrate to regional lymph nodes and mature in vivo, or they can be administered after in vitro maturation (mature dendritic cells, mDC). These two therapeutic modalities were compared in 19 pts with advanced melanoma or renal cell carcinoma (RCC) using iDC or mDC pulsed with autologous tumor lysate (ATL) and keyhole limpet hemocyanin (KHL), administered intradermally (id). Methods: DC were obtained from adherent mononuclear cells cultured with IL-4 and GM-CSF.ATL and KLH were added on the 6th day. On the 7th day iDC were used to vaccinate 9 pts, while mDC, obtained by a further 48-h culture with IL-1β, IL-6, TNFα and PGE2, were used in 10 pts. Results: Of the 9 pts (8 melanoma,1 RCC) treated with iDC, 4 showed stable disease (SD) of 19, 6, 6, 6 months' duration and 5 progressed (P). Four of the 9 pts had weak delayed-type hypersensitivity (DTH) skin reactions for KLH or ATL. Of the 10 pts (9 melanoma and 1 RCC) treated with mDC, there was 1 complete response (CR) (abdominal lymph nodes) of 10+ months' duration, with positive DTH for both ATL and KLH and onset of vitiligo,1 partial response (PR) (lung and lymph nodes) of 3 months' duration, with subsequent development of brain metastases, 1 mixed response (MR) (skin and lymph nodes) lasting 6 months with positive DTH for both ATL and KLH and subsequent development of brain metastases, 3 SD of 9 (RCC patient), 9 and 7+ months' duration with positive DTH for KLH (1 pt progressed with brain metastases), and 4 P (1 brain metastases), all with negative DTH for ATL. Conclusions: Intradermally administered mDC appear to have a more important therapeutic potential than iDC for anticancer vaccination. Results could be optimized by improving times and modalities of in vitro maturation, with a more specific selection of pts (more immunoresponsive and/or with minimal residual disease) and perhaps with chemoprevention of brain metastases. Partially financed by Ministry of Health Research Projects 2000, n. 352 and 2002, n.234. No significant financial relationships to disclose.
Uridine glucuronosyltransferase 2B7 pharmacogenetics predicts epirubicin clearance and myelosuppression
Authors: M. B. Sawyer, S. Damaraju, E. Pituskin, V. Damaraju, A. G. Scarfe, R. B. Bies, J. Hanson, M. Clemons, M. Kuzma, J. R. Mackey
Journal: Journal of Clinical Oncology (2009)

2504 Background: Epirubicin (EPI) is widely used to treat breast cancer. EPI is predominantly metabolized by uridine glucuronosyltransferase (UGT) 2B7 to inactive glucuronides. We previously showed that a UGT enhancer single nucleotide polymorphism (SNP) at position -161 T to C correlated with rates of morphine glucuronidation. Methods: We performed a prospective pharmacogenetic study of effects of this SNP on EPI metabolism in M0 breast cancer patients (PTS) receiving adjuvant or neoadjuvant FEC100 (5-fluorouracil 500 mg/m 2 , EPI 100 mg/m 2 and cyclophosphamide 500 mg/m 2 ) given every 3 wks. PTS with ALT and AST ≤ upper limit of normal (ULN), a total bilirubin ≤ ULN, and normal renal and cardiac function were eligible. EPI levels were drawn at approximately 1 and 24 hrs. Cycle 1 toxicities were assessed using NCIC CTG toxicity criteria. Results: 123 PTS entered this study, mean (range): age 51 (28 - 74), sex 122 F/ 1 M, baseline AST 24 U/L (13–66), ALT 22 U/L (5–90), bilirubin 8 μmol/L (2–26), creatinine 74 μmol/L (50 - 126). PTS were genotyped using Pyrosequencing; 26 PTS were TT homozygotes, 59 were CT heterozygotes, and 33 were CC homozygotes. 5 PTS could not be genotyped. A three compartment population pharmacokinetic model in NONMEM V 1.1 for EPI was used incorporating all PTS. The baseline objective function was 1817, and inclusion of genotype significantly improved the objective function to 1764; CC genotype PTS had decreased EPI clearance 88.9 L/hr compared to CT/TT genotype PTS 129 L/hr, p&lt;0.001. Rates of first cycle grade 3/4 leucopenia were 78% in CC PTS and 48% in CT/TT PTS; consistent with the pharmacokinetic analysis. Conclusions: A SNP in UGT 2B7 is common and appears to predicts EPI clearance and myelosuppresion in non-metastatic breast cancer PTS and may form the basis for a method to individualize EPI treatment. No significant financial relationships to disclose.
Prediction of complete remission in patients with refractory acute leukemia treated with AMSA.
Authors: E H Estey, M J Keating, T L Smith, K B McCredie, S S Legha, R S Walters, G P Bodey, E J Freireich
Journal: Journal of Clinical Oncology (1984)

The relation between characteristics known at start of therapy and response in 102 adults with refractory acute leukemia who received 4'-(9 acridinylamino)-methane-sulfon-m-anisidide (AMSA) was examined. Twenty-three (23%) of these patients attained complete remission (CR). Univariate analysis showed that the following characteristics were associated with CR: a fewer number of prior induction and maintenance regimens, a shorter time between latest relapse and AMSA therapy, the presence of Auer rods, a circulating blast cell count of less than 25,000/mm3, a marrow cellularity less than 90%, a ratio of marrow blasts and promyelocytes to more mature myeloid cells (differentiation ratio) less than 15, and a first-course AMSA dose of greater than or equal to 375 mg/m2. Some of these factors were interrelated. Multivariate analysis using logistic regression techniques was carried out to determine which of the above factors added independent prognostic information. This analysis produced a statistical model that related probability of response to the following in order of selection: Auer rod status, first-course dose, differentiation ratio, and absolute circulating blast cell count. Such a model could be useful in identifying patients with high, intermediate, or low probability of response to AMSA. AMSA could then be prescribed only for patients likely to respond while affording other patients alternate salvage programs at an earlier time.
No effect of low-intensity endurance exercise on muscle necrosis in the diaphragm of mdx mice
Authors: Monica Frinchi, Giuseppa Mudò, Francesca Rappa, Maria R. Bonsignore, Francesco Cappello, Natale Belluardo, Andrea Pace, Giuseppe Morici
Journal: European Respiratory Journal (2014)

Duchenne muscular dystrophy (DMD) is characterized by progressive skeletal muscle weakness. We have previously shown that low-intensity endurance training prevented muscle damage (Frinchi et al, Int J Sports Med 2014). Since the effects of low-intensity endurance training on the the diaphragm in the mdx mouse model are unknown, in the same animals we investigated Cx39 protein levels (Western blotting) in homogenates of the diaphragm before and after training. Mdx and wild-type (WT) mice were randomly assigned to sedentary (mdx-S, n=17; WT-S, n=19) or trained (mdx-EX, n=14; WT-EX, n=16) groups. Low-intensity endurance training (running on a wheel) was done 5 days/week for 6 weeks at progressively increasing time (15 min to 1 h) and speed (rpm from 16 to 24, distance covered during training sessions from 48 to 288 m). Compared to our previous analysis of skeletal muscles changes in gastrocnemius and quadriceps, showing decreased muscle damage in trained vs sedentary mdx mice, analysis of protein level of Cx39 showed similar values in diaphragm homogenates from sedentary and trained mdx mice.  These preliminary data suggest that prevention of muscle necrosis after mild training does not occur in the diaphragm. As a speculation, continuous work of diaphragm vs intermittent work of skeletal muscle might at least partly account for the different results obtained in respiratory and locomotor muscle.
Abstract 12547: Time-Course Influence of Brain Death on Cardiac Function and Its Impact on Posttransplant Graft Function
Authors: Shiliang Li, Sevil Korkmaz, Sivakkanan Loganathan, Tamás Radovits, Peter Hegedüs, Matthias Karck, Gábor Szabó
Journal: Circulation (2014)

Introduction: Heart transplantation became the most effective treatment for end-stage heart failure. Donors after brain death are currently the only reliable source for cardiac transplants. However, hemodynamic instability and cardiac dysfunction have been demonstrated in brain-dead donors and this could therefore also affect posttransplant graft function. Hypothesis: Our aims were to evaluate in rats the time-course cardiac influence of brain death and we tested the hypothesis that brain death impairs graft left ventricular function. Methods: Lewis rats were either maintained brain death for 5h by inflation of a subdurally placed balloon catheter (n=7) or subjected to sham-operation (control group, n=9). We continuously assessed cardiac function during 5 h. Then, hearts were excised, stored in cold preservation solution for 1 h, and heterotopically transplanted. We evaluated graft function 1.5 h after transplantation. Results: Brain death was associated with decreased left ventricular contractility (ejection fraction: 37±6% vs. 57±5%; dP/dt max : 4770±197 mmHg/s vs. 7604 ±348 mmHg/s; dP/dt max -EDV: 60±7 mmHg/s vs. 74±2 mmHg/s; E max : 2.4±0.1 mmHg/μl vs. 4.4±0.3 mmHg/μl; PRSW: 47±9 mmHg vs. 78±3 mmHg; p&lt;0.05) and relaxation (dP/dt min: -6638±722 mmHg/s vs. -11285±539 mmHg/s; Tau: 12.6±0.7 ms vs.10.5±0.4 ms; EDPVR: 0.33±0.14 mmHg/μl vs. 0.09±0.03 mmHg/μl, p&lt;0.05) 45 min after its initiation and for the rest of 5 h compared to controls. Moreover, after transplantation, graft systolic and diastolic functions were impaired in the brain-dead group compared to controls (reflected by decreased left ventricular systolic and developed pressures, dP/dt max and dP/dt min , and prolonged Tau). Conclusions: In conclusion, we have a well detailed characterized in vivo rat model to examine the influence of brain death on ventricular dysfunction using a microconductance catheter technology via pressure-volume analysis. These results demonstrate that brain death increases the susceptibility of donor heart to ischemia/reperfusion injury after transplantation.
A Phase 1 Study of Veliparib (Abt-888) in Combination with Carboplatin/Paclitaxel in Japanese Subjects with Non-Small Cell Lung Cancer (Nsclc)
Authors: H. Mizugaki, H. Nokihara, N. Yamamoto, Y. Fujiwara, H. Horinouchi, S. Kanda, S. Kitazono, S. Yagishita, H. Xiong, J. Qian, S. Shepherd, V.L. Giranda, T. Tamura
Journal: Annals of Oncology (2014)
Will the UK’s new alcohol guidelines change hearts, minds—and livers?
Authors: Theresa M Marteau
Journal: BMJ (2016)

The effects of fenbufen on the transport of ciprofloxacin (CPFX) into the brain and cerebrospinal fluid (CSF) were investigated in rats. Periodically after a bolus i.v. dose of CPFX (10 mg/kg), alone or with fenbufen (20 mg/kg), to rats, aliquots of CSF and blood were collected and then the whole brain was readily excised from the animal after sacrifice by microwave irradiation. Serum levels of CPFX in the terminal phase were significantly elevated by the coadministration with fenbufen. However, the extent of CPFX binding to serum protein was not affected by fenbufen. Immediately after the coadministration with fenbufen, brain and CSF levels of CPFX were raised by about 15 to 70% and 70 to 100%, respectively. Both brain/serum unbound and CSF/serum unbound level ratios were increased by fenbufen at relatively early periods after drug injection. Analysis based on physiological models indicated that fenbufen significantly increased the apparent diffusion clearances of CPFX across blood-brain and blood-CSF barriers. These findings suggest that coadministered fenbufen may facilitate the entry of CPFX into the central nervous system not only by elevation of serum level but also by enhancement of permeability across the blood-brain or blood-CSF barrier.
Cardioprotective activities of dexrazoxane (D), amifostine (A) and D,L-alpha-tocopherol (E) against cardiotoxicity of doxorubicin (Dx) alone and in combination with cyclophosphamide (C)
Authors: S. Radulovic, S. Bjelogrlic
Journal: Journal of Clinical Oncology (2004)

2118 Background: We compared the cardioprotective activities of D, A and E against cardiotoxicity of Dx alone and Dx in combination with C. Methods: BalbC female mice, 9 weeks old, were treated with Dx (10 mg/kg, iv) alone or with A plus C (150 mg/kg, ip), in single bolus doses (positive controls). In experimental groups, mice were pretreated with: 1. D (200 mg/kg, ip) 1 hour; 2. A (200 mg/kg, ip) half an hour; or 3. E (100 IU/kg, per os) 24 hours before Dx/Dx+C, respectively. AST, LDH, alpha-HBDH and CK serum activities were assayed 48 hours after. Animals were sacrificed 1.5 and 3 months after treatments and the heart muscle histopathology (HP) results were scored according to Billingham roles. Results: In animals treated with Dx alone, HP scores were 2.0 and 2.5 after 1.5 and 3 months and after Dx+C, 2.0 and maximal 3.0, respectively. D appeared to be the most active agent to inhibit the increase in all enzyme activities induced by Dx or Dx+C. According to HP scores D was more active compared to E or A. The HP scores were 1.0 after 1.5 and 3 months respectively when D were used before Dx, and 1.5 and 2.0 after 1.5 and 3 months respectively when used before Dx+C. E was surprisingly active against Dx induced HP changes, with Billingham scores 1.5 after 1.5 and 3 months. Conclusions: Cardioprotective activity of the investigated compounds could be ranged as :D>E>A. Biochemical parameters were less reliable then HP scores in investigating cardioprotective agents. Cardioprotective activity of E should be reinvestigated. A failed as cardioprotector, while D and E were effective against Dx alone only. Neither of the investigated protectors prevented cardiotoxic activity of Dx+C. No significant financial relationships to disclose.
Phase I results of RTOG L-0117; a phase I/II dose intensification study using 3DCRT and concurrent chemotherapy for patients with Inoperable NSCLC
Authors: J. D. Bradley, M. Graham, S. Suzanne, R. Byhardt, R. Govindan, J. Fowler, J. Purdy, J. Michalski, E. Gore, H. Choy
Journal: Journal of Clinical Oncology (2005)

7063 Background: The standard radiation dose for NSCLC was established by RTOG 7301 as 60 Gy. Local failure rates with this dose remain unacceptably high. Current cooperative group trials continue to use doses of 60–63 Gy in the setting of concurrent chemotherapy. The primary endpoint of the Phase I portion was to establish the maximum tolerated dose (MTD) of radiation therapy, in the setting of concurrent chemotherapy, using 3DCRT for NSCLC. Methods: Eligibility included patients with histologically proven, unresectable Stages I-III NSCLC and a Zubrod perfomance status of 0–1. Weight loss eligibility was ≤10%. Concurrent chemotherapy consisted of paclitaxel 50 mg/m2 and carboplatin AUC=2 given weekly. Radiation dose was to be sequentially intensified by increasing the daily fraction size starting at 75.25 Gy/35 fractions. Interim analysis was planned after the initial 7 patients were enrolled with application of the stopping rule if DLTs occurred in 2 or more patients. Radiation therapy volumes consisted of gross tumor and nodes plus a margin. Elective lymph nodes were not included in the treatment fields. Technical criteria included strict dosimetric constraints on the normal lung (V20 ≤30%) and esophagus (mean dose ≤34 Gy and V55 ≤ 30%) and water-based dose calculations prescribed to the isocenter. Results: The Phase I portion of this study accrued 17 patients from 10 institutions and was closed in January 2004. After the initial eight patients were accrued to Arm 1, the trial closed temporarily on September 26, 2002 due to reported toxicity. Two acute treatment-related DLTs were reported: a grade 5 and a grade 3 pneumonitis. Subsequent DLTs since closure of Arm 1 include a grade 3 late pneumonitis and a grade 4 pain toxicity. The protocol was revised to de-escalate the radiotherapy dose (74 Gy/37 fractions). Arm 2 accrued 9 patients. One patient on Arm 2 developed a grade 3 esophagitis. Conclusions: The MTD was determined to be 74 Gy/37 fractions (2.0 Gy per fraction) using 3DCRT with concurrent paclitaxel and carboplatin. The Phase II component of RTOG L-0117 remains open to accrual at 74 Gy. No significant financial relationships to disclose.
A multicenter prospective study of carboplatin and paclitaxel for advanced thymic carcinoma: West Japan Oncology Group 4207L.
Authors: Koji Takeda, Fumihiko Hirai, Takeharu Yamanaka, Kenichi Taguchi, Haruko Daga, Junichi Shimizu, Yoshihito Kogure, Tatsuo Kimura, Kaoru Tanaka, Yasuo Iwamoto, Akira Ono, Hidefumi Sasaki, Junya Fukuoka, Kenichi Nishiyama, Takashi Seto, Yukito Ichinose, Kazuhiko Nakagawa, Yoichi Nakanishi
Journal: Journal of Clinical Oncology (2013)

7529 Background: Thymic carcinoma (TC) is a rare malignant tumor originated within the thymus gland and is associated with a poor prognosis, differing from thymoma which is the most common type of thymic malignant neoplasm. No results of clinical trials focusing on TC have been reported. This single-arm study evaluated carboplatin and paclitaxel (CbP) in previously untreated patients (pts) with advanced TC. Methods: Pts with Masaoka’s stage III to IVb TC, ECOG PS 0 to 1, and more than 20 years old were eligible. The study treatment consisted of carboplatin (AUC 6) and paclitaxel (200 mg/m 2 ) every 3 weeks for a maximum of 6 cycles. The primary endpoint was objective response rate (ORR) by extramural assessment. Secondary endpoints included overall survival (OS), progression-free survival (PFS), and safety. All pts were followed-up until 24 months (mo) after last enrollment. Based on the SWOG 2-stage design, the planned sample size of 40 pts was determined to reject the ORR of 20% under the expectation of 40% with a power of 0.85 and a type I error of 0.05. Results: From May 2008 to November 2010, 40 pts were enrolled from 21 centers. Of 39 evaluable for analysis, the median age was 62 years (range, 36–84); 23/16 males/females; 3/10/26 with Masaoka’s stage III/IVa/IVb; 9/11/19 with squamous cell carcinoma/poorly differentiated neuroendocrine carcinoma/other types. The median number of cycles was 6. There was 1/13 complete/partial responses with an ORR of 36% (95% confidence interval [CI], 21-53%; P = 0.031). The median PFS was 8.1 mo (5.4-13.1 mo) while OS did not reach the median value. The 1-year and 2-year survival rates were 85% (95% CI, 69-93%) and 71% (95% CI, 54-83%), respectively. Major adverse event was grade 3-4 neutropenia in 34 pts (87%). Two cases (5%) of grade 3 febrile neutropenia, neuropathy, and arthralgia were observed, respectively. There was no treatment-related death. Conclusions: CbP showed higher efficacy in advanced TC as compared with anthracycline-based chemotherapy which is the current standard for the treatment of thymoma. Our results established that CbP, one of the standard treatments for non-small cell lung cancer, also serves as a key chemotherapy regimen for TC. Clinical trial information: UMIN000001358.
Serum Levels of Fibronectin and a Fibronectin-Like DNA-Binding Protein in Patients With Various Diseases&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: Todd, Heather D., Coffee, Marie S., Waalkes, T. Phillip, Abeloff, Martin D., Parsons, Robert G.
Journal: JNCI Journal of the National Cancer Institute (1980)

Journal Article Serum Levels of Fibronectin and a Fibronectin-Like DNA-Binding Protein in Patients With Various Diseases Get access Heather D. Todd, Heather D. Todd 4Biological Markers Program, NCI Frederick Cancer Research Center, P.O. Box B, Frederick, Md. 21701. Search for other works by this author on: Oxford Academic PubMed Google Scholar Marie S. Coffee, Marie S. Coffee 4Biological Markers Program, NCI Frederick Cancer Research Center, P.O. Box B, Frederick, Md. 21701. Search for other works by this author on: Oxford Academic PubMed Google Scholar T. Phillip Waalkes, T. Phillip Waalkes 5The Johns Hopkins Oncology Center, The Johns Hopkins Hospital, Baltimore, Md. 21205. Search for other works by this author on: Oxford Academic PubMed Google Scholar Martin D. Abeloff, Martin D. Abeloff 5The Johns Hopkins Oncology Center, The Johns Hopkins Hospital, Baltimore, Md. 21205. Search for other works by this author on: Oxford Academic PubMed Google Scholar Robert G. Parsons Robert G. Parsons 6 4Biological Markers Program, NCI Frederick Cancer Research Center, P.O. Box B, Frederick, Md. 21701. 6Address reprint requests to Dr. Parsons. Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 65, Issue 5, November 1980, Pages 901–904, https://doi.org/10.1093/jnci/65.5.901 Published: 01 November 1980 Article history Received: 24 April 1980 Accepted: 18 June 1980 Published: 01 November 1980
MPs pass innovative medicines bill
Authors: Clare Dyer
Journal: BMJ (2016)

A private member’s bill that would encourage UK doctors to try innovative treatments and consider the off-label use of drugs has passed its Commons stages with government support, and will go to the House of Lords.

The central plank of the Access to Medical Treatments (Innovation) Bill is a database that would let doctors search for drugs that are in clinical trials (for which their patients might be eligible) and drugs licensed to treat one condition that could be used for another.

The bill, proposed by the Conservative MP Chris Heaton-Harris, …