tbuckley/cabot-search huggingface dataset:
A phase Ib study of the MEK inhibitor GSK1120212 combined with gemcitabine in patients with solid tumors: Interim results.
Authors: A. W. Tolcher, J. C. Bendell, A. Patnaik, K. Papadopoulos, K. M. Bellew, D. S. Cox, Y. Xu, H. A. Burris, N. Le, J. R. Infante
Journal: Journal of Clinical Oncology (2011)

278 Background: GSK1120212 (212) is a reversible, allosteric inhibitor of MEK1/MEK2. The objectives of this open-label, single-arm study are to evaluate the safety, pharmacokinetics (PK), and anti-tumor activity of 212 + gemcitabine (gem), and to determine the recommended phase II regimen (RP2R) in patients (pts) with advanced solid tumors. Methods: 212 (1-2.5mg) is given continuously, orally, once daily. Gem (1,000mg/m 2 ) is infused on days 1, 8, and 15 every 28 days. Doses are escalated to the maximum tolerated dose (MTD) and followed by an expansion cohort to confirm the RP2R tolerability. Results: 28 pts received ≥ 1 dose of 212 + gem, including 8 pancreatic, 6 breast, and 4 non-small cell lung (NSCLC) cancer pts. The MTD and RP2R is 2mg 212 + 1,000mg/m 2 gem. Dose-limiting toxicities (DLTs) are G3/G4 febrile neutropenia (n=2), G3 AST elevation (n=2), and G2 uveitis (n=1). 16 serious adverse events (SAEs) were reported; 5 were considered to be related to study drugs (1 pneumonitis, 3 febrile neutropenia, 1 dyspnea). All DLTs and SAEs have resolved. The most common AEs at the RP2R (n=18) were rash (78%), fatigue (67%), thrombocytopenia (61%), neutropenia (50%), decreased appetite (50%), nausea (44%), diarrhea and constipation (39%); all ≤ G2 except thrombocytopenia (17% ≥ G3) and neutropenia (33% ≥ G3). Co-administration did not affect the PK profiles of 212 or gem. 25 pts had measurable disease at baseline. 1 pancreatic cancer pt with previous radiotherapy and 2 cycles of gem achieved a partial response and stayed on study for 6 months. 3 additional pancreatic cancer pts reported stable disease; 2 of which were on the study for 3.5-5 months and the third pt continues in the study. 1 triple-negative breast cancer pt, refractory to chemotherapy, and 1 parotid cancer pt experienced a complete response of their target lesions. Conclusions: 212 + gem is tolerable with an acceptable safety profile in this pt population, with evidence of clinical activity in pancreatic cancer. A randomized phase II study in previously untreated patients with metastatic pancreatic cancer is underway to investigate the clinical activity of this combination. [Table: see text]
Occupational and Environmental Medicine
Journal: JAMA (1998)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
The efficacy of EORTC risk tables in Japanese patients with non-muscle invasive bladder cancer.
Authors: Satoru Muto, Takeshi Ieda, Syou-ichiro Sugiura, Akiko Nakajima, Akira Horiuchi, Fumitaka Shimizu, Masahiro Inoue, Yasuo Noma, Kousuke Kitamura, Keisuke Saito, Shuji Isotani, Hisamitsu Ide, Raizo Yamaguchi, Shigeo Horie
Journal: Journal of Clinical Oncology (2014)

331 Background: To predict recurrence and progression of non-muscle invasive bladder cancer (NMIBC), EORTC risk tables are widely used worldwide. EORTC risk tables were, however, developed on the basis of individual data from 2,596 NMIBC patients included in seven special European Organization for Research and Treatment of Cancer trials. Therefore, it is not clear the efficacy of these risk tables in clinical practice, especially in Japan. I will report the recurrence and progression rate on the basis of EORTC risk tables in Japanese NMIBC patients. Methods: A retrospective analysis of 619 patients with NMIBC treated between January 1998 and 2012 was performed. Patients were divided into three groups on the basis of EORTC risk tables. We compared recurrence- and progression-free survival rates between groups. Recurrence- and progression-free survival was estimated using the Kaplan-Meier method. Results: We evaluated the clinical outcome of 1,032 TUR-Bt. The recurrence rate is 32.3% in low risk group (n=31), 44.5% in intermediate risk group (n=757), and 49.4% in high risk group (n=85). The median recurrence free survival time is 87 months in low risk group, 35 months in intermediate risk group, and 25 months in high risk group. Although there are significant differences in recurrence free survival time between low risk group and intermediate risk group (p=0.0351), there are no significant differences between intermediate risk group and high risk group (p=0.1871). On the other hand, the progression rate is 1.6% in low risk group (n=128), 5.8% in intermediate risk group (n=451), and 18.0% in high risk group (n=294). The median progression free survival time is 176 months in low risk group, 131 months in intermediate risk group, and 109 months in high risk group. There are significant differences in progression free survival time between low risk group and intermediate risk group (p=0.0138), and between intermediate risk group and high risk group (p=&lt;0.0001). Conclusions: There is an urgent need to establish the standard of recurrence risk classification in Japan.
13-year oncologic and functional outcomes and morbidity in men </= 55 years treated with I-125 brachytherapy +/- external beam radiation and/or androgen deprivation.
Authors: Daniel Shasha, Robert Salant, Ahalya Sivathayalan, Patrick Farrell, Philippa Cheetham, Louis B Harrison
Journal: Journal of Clinical Oncology (2016)

121 Background: Young patients are most often recommended prostatectomy because few radiation series have reported long-term outcomes specifically for this age group. We now address that deficit by presenting single-institution 13-year oncologic outcomes and morbidity after I-125 prostate brachytherapy (BRT). Methods: Between 1998-2014, 227 patients &lt; 55 years were prospectively followed after PCa treatment with BRT +/- external-beam irradiation +/- androgen deprivation. NCCN risk stratification identified 99 low-, 51 intermediate-, 77 high- + very-high-risk patients treated. Endpoints include Phoenix biochemical control (BC), prostate-cancer-specific survival (PCSS), overall survival (OS), and urinary, bowel, and sexual complications. Results: With a minimum and median follow-up of 26 and 72.3 months, respectively the 13-year actuarial rate of BC, PCSS, and OS for low-risk disease: 97.8%, 100%, 100%, respectively; for intermediate-risk disease: 94.0%, 100%, 88.1%, respectively and for high + very-high-risk disease 83.6%, 89.9%, 77.6%, respectively. Only 3 patients died of prostate cancer. Multivariate analysis demonstrated race, EBRT use, ADT use, PSA &gt; 10, PSA &gt; 20, GS &gt; 7, T3a, T3b, smoking, diabetes as significant for BC and PCSS (p &lt; 0.05). Permanent incontinence occurred only in the one patient who underwent TURP, 4 transient urethral strictures were all successfully dilated, and no other grade 3 intestinal or urinary complications were reported. In the 77.5 % potent at baseline, preservation was reported at 5 and 10-years overall in 75.8 % and 54.6 %, and with PDE5-I, 83.3% preserved potency at 10-years. Conclusions: Patients &lt; 55 years achieve excellent and durable prostate cancer control at 13 years after I 125 BRT, most notably in high-risk, with prostate cancer specific mortality uncommon in all but very-high-risk group. Significant urinary or bowel morbidity is uncommon, and potency preservation is expected with PDE5-I. We conclude age &lt; 55 years should not be used to discriminate against LDRBT.
Gene expression analysis of hormone-refractory prostate cancer in transurethral resection samples
Authors: P. Albers, M. Thiele, O. Stoss, N. Jost, C. Schmidtgen, J. Rueschoff, T. Henkel
Journal: Journal of Clinical Oncology (2005)

4778 Background: After a mean of 15 months, patients with metastatic carcinoma of the prostate (CaP) develop resistance to hormone ablation therapy. However, the underlying molecular mechanisms are still unknown. Our goal is to identify the transcriptional changes that are characteristic for the transition to hormone resistant prostate cancer (HRPC) using oligonucleotide microarrays. A challenge for this approach is the availability of fresh frozen tissue material from patients with HRPC. Here we report the attempt to profile tissue obtained by palliative transurethral resection (TUR). Methods: Indications for palliative TUR were locally progressive tumors with obstruction and voiding problems. HRPC was defined according to the criteria of Scher et al. 1995. Hormone-sensitive CaP tissue has been obtained from patients with incidental CaP during TUR. Samples of benign prostatic hyperplasia (BPH) were collected from age-matched patients undergoing TUR. All tissue samples had been pathologically evaluated and immediately processed (< 10 min) after TUR. Only macrodissected prostate samples with at least 70% tumor content were used for analysis. Results: RNA was successfully isolated from BPH, hormone-sensitive CaP and HRPC samples using a modified purification protocol. The isolated RNA passed well defined quality criteria such as the 28S/18S rRNA ratio (>1,0) and the area under curve (AUC >20%) which were assessed using the Bioanalyzer Nanochip (Agilent Technologies, Palo Alto). Subsequently, RNA integrity was confirmed on human genome FOCUS arrays (Affymetrix Inc., Santa Clara). Conclusions: The reported feasibility of generating expression-profiles from BPH, PCA and HRPC transurethral resection samples now offers the possibility to reveal pathways leading to hormone resistance. Furthermore, the identification of chemopredictive and prognostic marker profiles seems possible. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Novartis Oncology
Primary non-Hodgkin lymphoma of the colon: A Veterans Affairs Central Cancer Registry analysis.
Authors: A. Wilkes, T. Tashi, J. Wolpert, A. Goshgarian, W. Gonsalves, R. Thota, J. Krishnamurthy, I. T. Aldoss, A. R. Sama, P. Townley, N. Didwaniya, A. K. Ganti, P. T. Silberstein, S. Subbiah
Journal: Journal of Clinical Oncology (2011)

e18525 Background: Primary non-Hodgkin lymphoma (NHL) of the colon represents less than 1% of all colonic neoplasms. Due to the rarity of this disease there is a lack of prospective randomized clinical trials, hence optimal treatment is uncertain. We provide the largest descriptive study of this tumor to date. Methods: Retrospective analysis of 109 patients diagnosed with primary non-Hodgkin lymphoma of the colon from 1995 to 2008 was done via the Veteran's Affairs Central Cancer Registry. By definition, all cases presented with a lymphomatous involvement of the colon as the first manifestation of their disease with no previous diagnosis of NHL of any type or site. Lymphomas were classified as aggressive or indolent based on their histology. Demographic, staging, histology, treatment, and outcome data was recorded. Results: There were 36,260 colon cancers diagnosed in 1995-2008 of which 109 (0.3%) were primary non-Hodgkin colon lymphomas. Median age of diagnosis was 67 years. 55 pts had aggressive disease, 27 pts had indolent disease, and 27 pts had inadequate histological data. Diffuse large B cell lymphoma (73%) was the most common aggressive lymphoma whereas marginal zone (56%) was the most common in the indolent group. The indolent group had 5-year survival rate of 76.9% compared to 48.6% for the aggressive group. Both groups received a variety of treatment regimens as seen in the table below with variable survival outcomes. Conclusions: Our data suggests addition of adjuvant chemotherapy improved survival compared to surgery alone in the treatment of aggressive disease. Multimodality therapy does not appear to provide any benefit in the treatment of indolent disease. However, patient numbers are too small to draw definite conclusions and warrant future investigation in a multinational randomized fashion. Treatment modality No (%) Survival (mos) Indolent group No treatment 13 (48%) 65.5 Surgery 8 (30%) 82.5 Chemotherapy 3 (11%) 60.4 XRT 1 (4%) 52.9 Surgery + adj chemotherapy 2 (7%) 32.4 Aggressive group No treatment 6 (11%) 3.5 Surgery 12 (22%) 47.8 Chemotherapy 9 (16%) 42.3 Surgery + adj chemotherapy 25 (45%) 98.6 Chemotherapy + XRT 2 (4%) 27.6 Surgery + adj chemotherapy/XRT 1 (2%) 22.3
Macrophage phenotypes and their expression in non-small cell lung cancer
Authors: C. Ohri, A. Shikotra, D. Waller, P. Bradding
Journal: Journal of Clinical Oncology (2008)

22132 Background: The role played by the innate immune system in determining survival from non-small cell lung cancer (NSCLC) is unclear. There is a survival advantage for patients with NSCLC expressing high numbers of macrophages in their tumour islets. The aim of this study was to investigate the immunological phenotype of islet and stromal macrophages in NSCLC. Methods: We used double-stain immunohistochemistry to identify CD68+ macrophages along with markers of either the non-cytotoxic M2 phenotype (CD163), or the cytotoxic M1 phenotype (HLA-DR,inducible nitric oxide synthase (iNOS), myeloid-related protein 8/14 dimerisation (MRP 8/14) and tumour necrosis factor-alpha (TNFα). This was performed on surgically resected tumours for 20 patients with good survival (median 92.7 months) compared to 20 patients with poor survival (median 7.7 months). Results: CD68+ macrophages were detected in both the tumour stroma and islets in all patients. There were significantly more double-stained CD68+ macrophages for all five phenotypes (11.5 cells/mm2 for CD163, 13.2 for HLA-DR, 21.6 for iNOS, 22.5 for MRP and 16.9 for TNFα) in islets of patients with > median survival compared with patients with < median survival (3.4, 3.9, 1.8, 2.9 and 3.7 cells/mm2 respectively) (p≤0.001). Conversely, there was no significant difference noted for the densities of these double-staining cells in the two survival groups in the stroma. Putative M1 macrophages were significantly increased compared to M2 macrophages in the islets of the good prognosis group (p≤0.05 for each marker). Conclusion: Macrophages in the tumour islets of patients with NSCLC express predominantly markers of the cytotoxic M1 macrophage population (HLA-DR, iNOS, MRP 8/14 & TNFα). This supports the view that the extended survival associated with islet macrophage infiltration is due to the cytotoxic anti-tumour activity of this macrophage population. No significant financial relationships to disclose.
A phase I-II open-label trial of ispinesib on an alternate dosing schedule in chemotherapy-naive patients with locally advanced or metastatic breast cancer (MBC)
Authors: M. Philco, S. Falcon, H. Gomez, R. Escandon, K. Saikali, A. Wolff
Journal: Journal of Clinical Oncology (2008)

1143 Background: Kinesin spindle protein (KSP) is a mitotic kinesin essential for cell cycle progression. Ispinesib, a selective KSP inhibitor, blocks mitotic spindle assembly with cell cycle arrest in mitosis and subsequent cell death. In the first-in-humans trial, the maximum tolerated dose (MTD) was 18 mg/m2 q21 days (d). Neutropenia, the dose-limiting toxicity (DLT), reached nadir at 7–10 d and recovered fully by d15. Other toxicities ≥ grade 3 were uncommon and unrelated to dose. A prior phase II trial evaluating ispinesib at 18 mg/m2 q21d in patients (pts) with locally advanced or MBC which recurred or progressed after treatment with anthracyclines and taxanes identified partial responses (RECIST) in 4 of 45 evaluable pts in this heavily pre-treated population. Ispinesib was also well tolerated in this trial; neutropenia again reached nadir at 7–10 d and recovered by d15 with no cumulative effect, suggesting ispinesib may be given on d1 and d15 q28d, thus increasing dose density (and possibly efficacy) while maintaining favorable tolerability. Methods: Phase I of this trial determines the DLT and MTD of ispinesib given d1 and d15 q28d as 1st-line therapy for locally advanced (Stage IIIB) or MBC (Stage IV). Pts are either chemotherapy-naïve or ≥ 1 year has elapsed since adjuvant or neoadjuvant treatment with anthracycline-based chemotherapy. Ispinesib is given to cohorts of 3 pts on d1 and d15 q28d, starting at 10 mg/m2 and escalates based on tolerability. A cohort expands to 6 pts if 1/3 pts have a DLT. Phase II of this trial evaluates the potential efficacy of ispinesib at the phase I MTD in pts with locally advanced or MBC who have had no prior chemotherapy. The primary endpoint is response rate by RECIST. Results and Conclusions: Enrollment initiated with ispinesib at 10 mg/m2 given d1 and d15 q28d. Data from phase I (DLT, MTD, and potential efficacy) will be presented. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration Cytokinetics
The accuracy of tobacco assessment during definitive radiotherapy or chemoradiotherapy in patients with head and neck cancer.
Authors: M. R. Kudrimoti, S. M. Arnold, J. Valentino, T. Gal, A. Hyland, A. Singh, V. Rangnekar, K. M. Cummings, J. R. Marshall, G. W. Warren
Journal: Journal of Clinical Oncology (2011)

1556 Background: The accuracy of self-reported (SR) tobacco use at the time of cancer diagnosis and during treatment and the utility of biochemically confirmed (BC) tobacco use assessment during cancer treatment has not been established. Methods: Patients with squamous cell carcinoma of the head and neck treated with definitive radiotherapy or chemoradiotherapy (CRT) were eligible for voluntary unpaid enrollment on an Institutional Review Board approved study. Structured entry and weekly SR tobacco use was obtained and weekly patient serum was obtained for BC assessment using serum cotinine. Results: Of 50 patients, median age is 56, 80% are male, 92% are Caucasian, 92% are stage III-IVB, 92% have laryngeal or oropharyngeal cancer, and 84% were treated with CRT. Any tobacco use history was reported in 82%. At baseline, 39% of patients SR current tobacco, but 46% had BC tobacco use. The accuracy of tobacco use during treatment based upon baseline SR tobacco assessment ranged from 73-92%, but weekly SR tobacco assessment increased accuracy to between 85-92%. In patients with current SR tobacco use at baseline, 63% tested positive by BC during the final week of treatment. In patients who denied SR tobacco use at baseline, 16% tested positive by BC and 7% tested positive by BC during the final week of treatment. The average positive predictive value of weekly SR was 92% and the average negative predictive value of weekly SR was 87%. Evaluation of patient specific SR characteristics over the course of treatment demonstrates a consistent group of patients who repeatedly misrepresent weekly SR tobacco use. Weekly secondhand smoke exposure was higher (range 31-61%) in patients who report current SR tobacco use at diagnosis as compared with patients who deny SR tobacco use at diagnosis (range 7-19%). Patient compliance for completion of all assessments was 93%. Conclusions: Repeated SR tobacco use assessment during cancer treatment increases the accuracy of identifying true tobacco use as compared with baseline assessment alone, but BC assessments may be necessary to detect true tobacco use status in a subset of patients who consistently misrepresent SR tobacco use. Patient compliance for BC assessment was high.
Therapeutic choices for patients with hemophilia and high‐titer inhibitors
Authors: Roshni Kulkarni, Louis M. Aledort, Erik Berntorp, Hans H. Brackman, Deborah Brown, Alan R. Cohen, Nadia P. Ewing, Alessandro Gringeri, Ralph Gruppo, Keith Hoots, Cindy Leissenger, Katheliijne Peerlinck, Man‐Chiu Poon, Wing‐Yen Wong
Journal: American Journal of Hematology (2002)
In-breast tumor recurrence rate of breast CT-guided lumpectomy: A prospective multi-institutional study in Japan.
Authors: Nobuaki Sato
Journal: Journal of Clinical Oncology (2012)

170 Background: We have conducted the prospective multicenter study to evaluate the usefulness of breast CT in delineating tumor extent and preoperatively determining the optimal surgical procedure (Sadako Akashi-Tanaka et al, Ann Surg in press). Breast CT, carried out in the supine position, was useful since breast CT correctly changed the extent of surgery in 13.1% of patients. Here, we present the in-breast tumor recurrence (IBTR) of these patients undergoing CT guided breast conserving surgery. Methods: The follow-up records of 271 women treated with local excision (complete removal of gross tumor with a margin) for breast cancer at 3 Japanese hospitals were reviewed. CT guided surgery was performed as follows; the surgeon marked the line of planned excision prior to CT on the skin, which was also recorded on the CT image. Contrast-enhanced breast CT was performed in the supine surgical position. The CT results were used to determine the extent of surgery. IBTR was defined as a recurrence in the treated breast without regional or distant metastases. Results: The median age at surgery of them was 55 years (range, 21 to 88 years). The median palpable tumor size was 1.6cm (range, 0 to 3.5 cm). Tumor histology was as follows: ductal carcinoma in situ 13, invasive ductal carcinoma 234, invasive lobular carcinoma 10, mucinous carcinoma 6, and special type 8. The median follow-up after treatment was 3.8 years (range, 3.0 to 5.3 years). The rate of IBTR was 10/271 (3.7%). The 3.8-year rate of IBTR was 4.5%. Discussion: Without prospective randomized controlled studies, it is unlikely that a definitive conclusion can be reached on whether imaging-guided diagnosis of tumor extent will reduce the rate of IBTR. However, it seems almost ethically impossible to conduct such a clinical study in Japan, because preoperative imaging-guided diagnosis of tumor extent is routinely performed prior to surgery. Conclusions: Although this was not the randomized controlled study, CT-based preoperative diagnosis of tumor extent has the potential to improve the accuracy of breast-conserving surgery. The long-term results of IBTR need to be assessed.