tbuckley/cabot-search huggingface dataset:
Phase II trial of elesclomol (formerly STA-4783) and paclitaxel in stage IV metastatic melanoma (MM): Subgroup analysis by prior chemotherapy
Authors: R. Gonzalez, D. H. Lawson, R. W. Weber, L. F. Hutchins, C. M. Anderson, K. N. Williams, S. Kong, E. Jacobson, S. J. O’Day
Journal: Journal of Clinical Oncology (2008)

9036 Background: Elesclomol is a novel small-molecule oxidative stress inducer known to synergize with taxanes and certain other chemotherapeutics. Our previously reported 2:1 randomized, double-blinded, placebo-controlled Phase 2 trial of 213 mg/m2 elesclomol co-infused with 80 mg/m2 paclitaxel (E+P) vs. paclitaxel alone (P) in Stage IV MM showed E+P to be tolerable and demonstrated increased median progression-free survival (PFS) and overall survival (OS) for E+P-treated patients (pts). We now report response by prior chemotherapy. Methods: This 21-site study compared E+P (52 pts planned) with P alone (26 pts planned). Pts received 4-week cycles of once weekly E+P or P for 3 weeks and 1 week’s rest until disease progression. Eligible pts with Stage IV MM, 1 or 0 prior chemotherapies, any number of biologic therapies, and ECOG ≤ 2 were evaluated every 8 weeks for progression per RECIST. P-treated pts were eligible for post-progression crossover to E+P. The primary endpoint was PFS; follow-up OS data were analyzed. Additional prior therapy data collection and subset analyses were post hoc. Results: For the chemotherapy naïve group, E+P pts had a statistically significant reduction (69%) in the risk of progression or death, as well as a 5-month extension of median OS compared to P pts. Conclusions: PFS and OS results warrant further study of E+P in MM, especially in chemotherapy-naïve pts. For this subset, reported PFS and OS notably exceed historical data. A multinational Phase 3 trial of E+P vs. P (SYMMETRY) is now enrolling chemotherapy- naïve pts with stage IV MM. Subgroup * E+P chemo**-naive P‡ chemo-naive E+P 1 prior chemo P† 1 prior chemo n 25 8 28 20 Median PFS¶ (95% CI) 7.1 mo. (3.5–9.1) 1.8 mo. (1.6–3.4) 2.8 mo. (1.8–4.4) 1.8 mo. (1.6–3.5) Hazard ratio (P-value) 0.313 (0.019)§ 0.838 (0.568) Median OS¶ (95% CI) 15.1 mo. (8.5–19.4) 10.0 mo. (5.1-unk.) 9.0 mo. (6.4–23.4) 7.8 mo. (4.8–16.9) * Intent-to-Treat; ** cytotoxic(s) for metastatic disease; † Of these 15/20 crossed over to E+P; ‡ Of these 4/8 crossed over to E+P; ¶ From randomization; § Cox modeling adjusted for LDH, liver metastases, and M1 grade yields HR 0.147, P = 0.024 Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration Synta Synta Synta Synta Synta
Activity and safety of carboplatin and paclitaxel followed by capecitabine and radiation as adjuvant therapy for gastric cancer (GC)
Authors: M. Mobayed, P. A. Philip, A. F. Shields, L. Heilbrun, T. Washington, U. Vaishampayan, R. Venkatramanamoorthy, B. F. El-Rayes
Journal: Journal of Clinical Oncology (2007)

15162 Background: Adjuvant 5FU based chemo-radiotherapy is considered the standard of care for the treatment of GC. However, the reduction in distant metastases has not been significant indicating the poor systemic effect of this regimen. A regimen of carboplatin and paclitaxel followed by capecitabine and radiation was adopted at the Karmanos Cancer Institute to improve the systemic effects of adjuvant therapy and to utilize the significant antitumor effects of taxanes demonstrated in advanced GC. Methods: We reviewed the outcomes of 21 consecutive patients with GC who were treated with carboplatin (AUC 5 mg/ml x min) and paclitaxel (175–200 mg/m2), followed by concurrent capecitabine (1600–2000 mg/ m2) and radiation (45–50.4 Gy) since January, 1999 for curatively resected GC. Patients received a total of 4–6 cycles of carboplatin and paclitaxel. Results: The median age at diagnosis was 60 years old. Sixteen patients had stage 3 disease and 7 of them had positive margins (R1/R2 resection), 3 patients were stage 2 and 2 patients were stage 1 and both groups had negative margins; all patients had D1/D2 lymph node dissection. Thirteen patients had recurrent disease, 10 of whom had distant metastases. The median recurrence free survival was 12.3 months (90% CI; 9.7–27.7 months). Seven patients are still alive. The median OS was 16.0 months (90% CI; 13.3- 28.8 months). The median follow up for OS was 30.4 months. Grade 3–4 hematologic toxicities were found in 7 patients (33.3 %). Non-hematologic toxicities included grade 3 diarrhea in 3 patients (14%), severe fatigue in 2 patients (10%). No treatment related deaths were observed. Conclusions: Carboplatin and paclitaxel alongside radiation plus capecitabine is a well tolerated regimen in the adjuvant setting. The activity of this regimen in this relatively high risk group of GC patients is of interest for future development. No significant financial relationships to disclose.
Changes in Body Mass Related to the Initiation of Disease‐Modifying Therapies in Rheumatoid Arthritis
Authors: Joshua F. Baker, Brian C. Sauer, Grant W. Cannon, Chia‐Chen Teng, Kaleb Michaud, Said Ibrahim, Erik Jorgenson, Lisa Davis, Liron Caplan, Amy Cannella, Ted R. Mikuls
Journal: Arthritis & Rheumatology (2016)

Unintentional weight loss is important and can be predictive of long-term outcomes in patients with rheumatoid arthritis (RA). This study was undertaken to assess how primary therapies for RA may influence changes in body mass index (BMI) in RA patients from a large administrative database.Unique dispensing episodes of methotrexate, prednisone, leflunomide, and tumor necrosis factor inhibitors (TNFi) administered to RA patients were identified from the US Department of Veterans Affairs pharmacy databases. Values for C-reactive protein (CRP) level and BMI closest to the time point within 30 days of the treatment course start date and at follow-up time points were linked. Missing laboratory values were imputed. Weight loss was defined as a decrease in BMI of >1 kg/m(2) . Regression models were used to evaluate changes in BMI during each drug treatment as compared to treatment with methotrexate. To assess the impact of confounding by indication, propensity scores for use of each drug were incorporated in analyses using matched-weighting techniques.In total, 52,662 treatment courses in 32,859 RA patients were identified. At 6 months from the date of prescription fill, weight gain was seen among patients taking methotrexate, those taking prednisone, and those taking TNFi. On average, compared to methotrexate-treated patients, prednisone-treated patients had significantly more weight gain, while leflunomide-treated patients demonstrated weight loss. In multivariable models, more weight loss (β = -0.41 kg/m(2) , 95% confidence interval [95% CI] -0.46, -0.36; P < 0.001) and a greater risk of weight loss (odds ratio 1.73, 95% CI 1.55, 1.79; P < 0.001) were evident among those receiving leflunomide compared to those receiving methotrexate. Treatment with prednisone was associated with greater weight gain (β = 0.072 kg/m(2) , 95% CI 0.042, 0.10; P < 0.001). These associations persisted in analyses adjusted for propensity scores and in sensitivity analyses.Leflunomide is associated with significantly more, but modest, weight loss, while prednisone is associated with greater weight gain compared to other therapies for RA.
Abstract 187: αB-crystallin Interacts And Prevents Stress-activated Proteolysis Of Focal Adhesion Kinase In Cardiomyocytes
Authors: Aline M dos Santos, Michelle B Pereira, Danieli C Gonçalves, Alisson C Cardoso, Silvio R Consonni, Fabio C Gozzo, Paulo S Oliveira, Alana R Figueiredo, André A de Thomaz, Carlos L Cesar, Carlos H Ramos, Kleber G Franchini
Journal: Circulation Research (2014)

Focal adhesion kinase (FAK) contributes to cellular homeostasis under stress conditions. Here, we show that αB-crystallin confers protection to FAK against calpain-mediated proteolysis under mechanical stress in cardiomyocytes. Biochemical assays, chemical cross-linking coupled to mass spectrometry experiments, mutational analyses and Förster resonance energy transfer (FRET) were combined to investigate the basis of FAK and αB-crystallin interaction. A hydrophobic patch mapped between helices 1 and 4 of the FAK FAT domain was found to bind to the β4-β8 groove of αB-crystallin. Such an interaction requires FAK tyrosine 925 and is enhanced following its phosphorylation by Src, which occurs upon FAK stimulation by mechanical stress. αB-crystallin silencing results in calpain-dependent FAK depletion and in increased apoptosis of cardiomyocytes. The overexpression of a myc-FAK construct or treatment with a calpain inhibitor (E64) restored the survival of cardiomyocytes depleted of αB-crystallin. The association between FAK and αB-crystallin was also demonstrated to occur in response to pressure overload in rat left ventricle. The myocardial depletion of αB-crystallin by siRNA results in enhanced apoptosis of cardiomyocytes and myocardial fibrosis in overloaded hearts. These alterations were markedly attenuated in the overloaded left ventricles of transgenic mice with cardiac specific FAK expression. These findings define a novel mechanism by which αB-crystallin controls FAK function, with impact on cardiomyocyte survival and cardiac remodelling in response to stress.
Gastrointestinal stromal tumors: A monoinstitutional experience
Authors: M. Di Battista, M. A. Pantaleo, M. Astorino, G. Brandi, M. Saponara, V. Di Scioscio, D. Santini, P. Castellucci, F. Catena, G. Biasco
Journal: Journal of Clinical Oncology (2007)

15161 Background: Optimal management of GIST pts required a multidisciplinary approach. Novel tyrosine kinase inhibitors provide an improvement of disease treatment. Methods: We report the clinical results of 67 pts treated in our institution from January 2003 to October 2006, including 41 men and 26 women. Their ages ranged from 28 to 86 yrs (mean 65). 24% of pts were classified into low risk categories, 22% intermediate risk, 54% high risk. At diagnosis, 53/67 patients (79%) presented a localized disease and underwent to surgery, and 14/67 patients (21%) patients presented a metastatic disease. Among these 14 metastatic patients, 8 underwent to surgical removal of primary tumor and metastatic site before treatment with imatinib (2 patient R0) and 6 patients were inoperable at diagnosis and received treatment with imatinib. In total, 61/67 (91%) of patients underwent surgery, R0 resection was achieved in 51 patients. Among 61 operated patients, 24 patients developed a recurrence and received medical treatment with Imatinib. In total, 30/67 (44,7%) patients were treated with Imatinib, and 27 were enrolled in a clinical studies of second line treatment with Sunitinib because of progression or intolerance to treatment with Imatinib. Results: After a follow-up of 42 months we report a median DFS of 14.5 months for radically operated patients. The 3 year-DFS rate was 28.6%. The differential analysis according to risk showed a median DFS of 16.5 months with 16.7% of pts disease free at 3 yrs for the high risk category (36 pts); in the low-intermediate risk categories (31 pts), a median DFS of 21 months with 38% of patients disease-free at 3 yrs was observed. Considering all 38 metastatic pts, 14 at diagnosis and 24 with recurrence, a progressive disease was seen in 94% (median 12 months). In first line of treatment with Imatinib we recorded a median TTP of 17 months with 30% of responders after 2 yrs of treatment. Conclusions: Surgery remains the only curative treatment for localized disease. imatinib is the standard of care for patients with metastatic Gist. For imatinib-resistant GISTs a novel agent such as Sunitinib appears promising. No significant financial relationships to disclose.
Matrix Metalloproteinase Inhibition of Pancreatic Cancer: Matching Mechanism of Action to Clinical Trial Design
Authors: Kenneth R. Hess, James L. Abbruzzese
Journal: Journal of Clinical Oncology (2001)

Article Tools EDITORIAL Article Tools OPTIONS & TOOLS Export Citation Track Citation Add To Favorites Rights & Permissions COMPANION ARTICLES No companion articles ARTICLE CITATION DOI: 10.1200/JCO.2001.19.15.3445 Journal of Clinical Oncology - published online before print September 21, 2016 PMID: 11481348 Matrix Metalloproteinase Inhibition of Pancreatic Cancer: Matching Mechanism of Action to Clinical Trial Design Kenneth R. HessxKenneth R. HessSearch for articles by this author , James L. AbbruzzesexJames L. AbbruzzeseSearch for articles by this author Show More University of Texas M.D. Anderson Cancer Center, Houston, TX https://doi.org/10.1200/JCO.2001.19.15.3445 Full Text PDF Figures and Tables "Matrix Metalloproteinase Inhibition of Pancreatic Cancer: Matching Mechanism of Action to Clinical Trial Design." Journal of Clinical Oncology, 19(15), pp. 3445–3446© 2001 by American Society of Clinical Oncology
Antibodies to HTLV-III/LAV in Venezuelan Patients with Acute Malarial Infections
Authors: D J Volsky, Y T Wu, M Stevenson, S Dewhurst, F Sinangil, F Merino, L Rodriguez, G Godoy
Journal: New England Journal of Medicine (1986)

Malarial infections have been associated with an immunosuppressive state similar to that seen in acquired immunodeficiency syndrome (AIDS).  Its manifestations include severe lymphopenia depletion of the T4-lymphocyte subset activation of B cells and diminished in vitro lymphocyte responses.  Because of these similarities the authors tested Venezuelan patients with acute malaria for antibodies to human T-lymphotropic virus type III (HTLV-III).  The sample included 12 patients with acute Plasmodium vivax infection and 12 with P. falciparum infection.  None of the patients were receiving antimalarial drugs and none belonged to any of the recognized risk groups for AIDS.  3 of the patients with P. falciparum infection (25%) and 5 with P. vivax (41%) were found to be positive for HTLV-III antibodies by indirect immunofluorescence.  Western blot and radioimmunoprecipitation tests.  The pattern of the Western blot and radioimmunoprecipitation bands obtained with samples from malaria patients was similar to that noted in AIDS patients.  Since acute malaria does not evolve into an AIDS-like syndrome it is concluded that exposure to HTLV-III and the occurrence of severe immunoregulatory disturbances are not always sufficient for the induction of AIDS.
The Safety of Eribulin for Breast Cancer Patients with Child-Pugh a Liver Dysfunction
Authors: Akihiko Shimomura, Yuji Miura, Kahori Fukushi, Tadaaki Ito, Koichi Suyama, Daishu Miura, Hidetaka Kawabata, Masahiro Hayashi, Toshimi Takano
Journal: Annals of Oncology (2014)
Pyridoxine and oestrogen-induced glucose intolerance. [Letter]
Authors: Cornish Ej, Tesoriero W
Journal: BMJ (1975)

Clinical examination of the possibility that xanthurenic acid is the cause of oral contraceptive (OC) induced glucose tolerance and gestational diabetes has been carried out.  The reduction by pyridoxine of excessive xanthurenic acid excretion following a tryptophan load has been associated with an improvement in glucose tolerance yet it is not believed that the 2 are causally related.  Instead the beneficial effects of pyridoxine are possibly because of normalization of other tryptophan metabolites.  Some women suffer from estrogen-induced glucose intolerance independent of any abnormalities in xanthurenic acid excretion.  It has been found that the administration of xanthurenic acid 120 mg/kg intraperitoneally in ammoniated saline failed to alter blood glucose in male Sprague Dawley or Wistar rats.  The experiments were repeated using the special high fat diet which had been used in the original studies on the diabetogenic effects of xanthurenic acid and xanthurenic acid was found to be inactive.  Xanthurenic acid did not impair glucose tolerance when given 1 hour before an oral glucose load in further experiments.  The failure to demonstrate any diabetogenic effect of xanthurenic acid could not be because of contamination with the 8-methyl ether of xanthurenic acid which has been reported to be antidiabetogenic since the sample of xanthurenic acid used was found to be free from this contaminant.
A retrospective review of the efficacy of gefitinib in the treatment of NSCLC in Lebanon
Authors: A. Shamseddine, K. Rashid, M. Ghoson, J. Kattan, N. Saghir, N. Bitar, G. Nsouli, W. Moukadem, G. Chahine, Z. Salem
Journal: Journal of Clinical Oncology (2005)

3217 Background: Gefitinib (Iressa) is a tyrosine kinase inhibitor belonging to the anilinoquinazoline class of compounds. It acts to inhibit the effect of EGFR, long recognized as the cellular homologue of the viral oncogene v-erb. Study Design: This study is a multi-center, retrospective review that aims to evaluate the Lebanese experience with gefitinib in the treatment of non-small cell lung cancer. Results: Among the 50 patients the mean age was 61 (median 64) 72% were male and 28% female. As for histological type, 15 patients (44.1%) had adenocarcinoma, 12 (35.3%) had squamous cell carcinoma, 2 (5.9%), 3(8.8%) and 2(5.9%) had non-small cell lung carcinoma, large cell, and epidermoid types respectively. 27 patients (54%) underwent radiation therapy and 12 (24%) had prior surgery. 45 patients (90%) had prior conventional chemotherapy which contained cisplatin in 35 (70%). 18 patients (36%) had 1 chemotherapy regimen before Iressa, 18 (36%) had 2 regimens, while 8 (16%) had 3 or more. Response rates to gefitinib were as follows: Complete response 2 patients (4%), partial response 4 (8%), with an overall response rate of 12%, stable disease 12 (24%) and progressive disease 29 (58%). When stratified by histology type, 14 patients had adenocarcinoma. Of those 1 had complete response, 2 had stable disease and 11 progressive disease while on gefitinib. Of the 25 patients who had ECOG functional status 0 or 1, 11 (44%) had disease progression vs 12 of the 15 patients (80%) who had ECOG functional status of 2 or more. (p = 0.046). This didn’t translate into survival benefit however with a survival time of 34 ± 7 months for ECOG functional status of 0 and 1 and 21± 4 months for ECOG functional status of 2 and above (p = 0.213). Conclusion: Despite the fact that the response rate to gefitinib is rather low (12%) it is higher for patients with ECOG functional status of 0 and 1 (p = 0.046) with a trend to improve survival among these patients (34 ± 7 vs 21± 4 months). No significant financial relationships to disclose.
Oral contraceptives and ovarian cancer [letter]
Authors: Casagrande Jt, Pike Mc, Henderson Be
Journal: New England Journal of Medicine (1983)

Cramer et al. reported the results of a case control study of ovarian cancer in women under age 60 indicating that oral contraceptive (OC) use was associated with a decreased risk of the disease.  Yet according to Cramer et al. the decreased risk was evident only in women over age 40 and that below this age OC use was actually associated with an increased risk of ovarian cancer.  As other workers had not broken down the data in this manner Cramer et al. were unable to compare this result with the results from other studies.  This group of researchers has reanalyzed their data to allow such a comparison.  In contrast to the results of Cramer et al. it was found that only in the young cases was their any possible negative association between OC use and ovarian cancer.  The data for both women under and over 40 showed a steady decrease in ovarian cancer with increasing duration of OC use.
Male gender, low education and cognitive deficit, but not advanced age, predict limited medical knowledge in elderly cancer patients
Authors: U. Basso, C. Pogliani, A. Brunello, L. M. Pasetto, E. Rossi, E. Lamberti, M. Toffanin, E. Capovilla, S. Monfardini
Journal: Journal of Clinical Oncology (2005)

8256 Background: Limited medical knowledge is a common finding in the elderly, who may be seriously hampered in their access to the health-care system due to shorter education and heterogeneous cognitive function. Objective and Methods: To assess the medical knowledge of elderly cancer patients (pts) by means of twenty multiple-choice questions dealing with the most frequent diseases of the older age, cancer screening, complications of chemotherapy, basic management of diarrhea, fever and infection. Twelve correct answers (60%) were chosen as an arbitrary dichotomizing cut-off level in order to test the different role of age (<75 vs ≥75), gender, level of education (more or less than five years of school) and cognitive function (Folstein’s MMS ≥24 vs 15–23) by means of a Chi-squared test. Results: 125 outpatients (72 of 65–74 years, 53 ≥75 years, 63.2% females) entering our Institution from March to October 2004 either for chemotherapy administration or follow-up visit, were interviewed directly by the treating physician. Sixty-seven percent had low education, but only 24% had a low MMS score. Only one third of men knew that PSA is a blood test related to the prostate gland, while 91.2% of women were well acquainted with mammography. Almost 10% erroneously believed that cancer may be a transmittable disease. One fifth knew the potential consequences of leukopenia and thrombocytopenia, more than a half were not aware of the need of huge hydration in case of severe diarrhea. While up to 72% could name an antipyretic drug, as low as 13.5% knew the trade name of an antibiotic. In the whole group, 35.2% of pts had an insufficient global score < 60%. Both short school education (p= .00) and low MMS score (p= .00) predicted a negative score, while age over 75 years did not (p= .37). In spite of education and MMS level being equally distributed among men and women, male gender predicted a higher chance of scoring negative (p= .02). Conclusions: Male gender, low education and MMS score, rather than chronological age in itself, may allow to identify elderly pts with limited medical knowledge, who are potentially at risk of not using preventive measures and of developing severe toxicities from cancer therapies. No significant financial relationships to disclose.