tbuckley/cabot-search huggingface dataset:
Phase I/II trial on TS-1 monotherapy for aged patients with advanced non-small cell lung cancer.
Authors: N. Nanki, Y. Ymaji, S. Bandoh, H. Miyawaki, Y. Ueda
Journal: Journal of Clinical Oncology (2010)

e18097 Background: Recently, the elderly population, including the number of elderly patients with lung cancer, has increased. Among the cases with advanced cancers, there are a number of patients for whom potent chemotherapy cannot be applied. TS-1 is an oral antitumor agent that combines tegafur, a prodrug of 5-FU, with gimeracil which inhibits dihydropyrimidine dehydrogenase activity, and oteracil potassium which reduces gastrointestinal toxicity, in a molar ratio of 1:0.4:1. The rate of response to treatment with TS-1 was reported to be 22% in patients with advanced non-small cell lung cancer (NSCLC). Thus it has been concluded that TS-1 monotherapy is one of the promising therapeutic modalities that can be applied to NSCLC. The purpose of the present study was to evaluate the safety of TS- 1 monotherapy applied as the initial treatment for advanced NSCLC in the oldest old, determine its recommended dosage (RD), and investigate the efficacy and safety of this RD. Methods: The subjects were those patients aged 75 years or older suffering from advanced NSCLC with PS 0-1 but without a severe organ dysfunction. Phase I: For the initial treatment, TS-1 monotherapy was conducted to estimate its RD. Phase II: The efficacy and safety of this TS-1 monotherapy were evaluated at the dosage determined above. TS-1 was administered via the oral route continually for 14 days, followed by withdrawal for 7 days. This regimen constituted one course. Drug administration was continued in this manner until PD was occurred or the standard for adverse effects forced drug withdrawal or the condition warranted it. Results: Consequent to Phase I trial, RD was determined to be 80 mg/m2. The trial was followed by phase II trial. There were 23 patients who were composed of the following: males (15) and females (8); age, 77 to 88 years (mean, 81.2); adenocarcinoma (19) and squamous cell carcinoma (4); neoplasm stages of IIIA (2), IIIB (6) and IV (15); PR, 10.5% (2 of 19 patients); DCR, 89.5% (16 of 19 patients); MST, 210 days. No serious adverse effects were noted in any of the 23 patients. Conclusions: This therapeutic modality may be safe and effective when applied to aged patients with advanced NSCLC. No significant financial relationships to disclose.
Intestinal current measurement (ICM) as a new diagnostic test for cystic fibrosis (CF)
Authors: Malena Cohen-Cymberknoh, Yasmin Yaakov, Eitan Kerem, David Shoseyov, Joseph Rivlin, Lea Bentur, Elie Picard, Micha Aviram, Michael Wilschanski
Journal: European Respiratory Journal (2011)

Background:  Like the nasal potential difference (NPD) test, ICM may be useful for the diagnosis of atypical CF. However, ICM is easily applicable at all ages.   Aim:  To assess the diagnostic reliability of ICM in a large cohort of CF, healthy control and patients with questionable CF.   Methods:  Rectal biopsies were taken from 3 groups: known CF patients, healthy controls and patients with questionable CF. The last group had a variety of symptoms suggestive of CF: recurrent pneumonia, unexplained bronchiectasis, chronic diarrhea and/or failure to thrive. ICMs were performed using standard protocols by mounting the rectal biopsy in an Ussing chamber and sequentially adding secretagogues while recording current changes.   Results:  17 known CF patients and 16 control patients were examined and have remarkably different results (all results are presented as μA/cm 2 ): carbachol 16±7, histamine 13±9 and forskolin 4.8±4 for healthy control group and carbachol -3.7±6.8 (p   Conclusion:  In this study we have shown that ICM tests may be useful to differentiate between CF and non-CF patients and may be included in diagnostic algorithms. Larger studies are needed to confirm these results.
Safety and tolerability of adjuvant exemestane plus goserelin with or without tibolone in receptor-positive, node-negative primary breast cancer in premenopausal women: The final results of the randomized multicenter ADAGIO pilot study
Authors: K. Pollow, W. Schoenegg, H. Koelbl, R. Kreienberg, A. Dubois, D. Elling, K.-J. Winzer, U. Koehler, G. Hoffmann
Journal: Journal of Clinical Oncology (2004)

594 Background: Goserelin (G) reduces ovarian production of luteinizing hormone and estrogen to postmenopausal values, but does not inhibit estrogens in peripheral tissues. Adding an agent that reduces peripheral estrogen production, such as the steroidal aromatase inactivator exemestane (E), may optimally decrease estrogen levels. The climacteric symptoms expected with a G/E regimen may be relieved with tibolone (T). The randomized, multicenter ADAGIO trial is testing the safety and tolerability of the combination of G and E, with or without T, in the adjuvant treatment of primary breast cancer in premenopausal women. We present the final results. Methods: Patients had histologically confirmed primary breast cancer (pT1, N0, M0 [grade 1–2]) and low or intermediate risk; they were age 35 to 55 years and estrogen- and/or progesterone-receptor positive. Patients were randomized to G 3.6 mg SC depot q 28 days for 6 doses; G and 2.5 mg E qd for 24 weeks; G and 1 tablet of 2.5 mg T; or G plus E plus T. Follow-up was 24 weeks; bone mineral density (BMD) was measured at baseline and week 24 by DEXA scan. Results: 47 patients (median age 44.1 years) were enrolled. Pretreatment characteristics were well balanced between the 4 groups. The combination of E and G did not decrease BMD more than G alone. The T arms showed a trend toward less decrease of BMD. There were no significant difference in adverse events (AEs) between the 4 arms, and no serious AEs were observed. Climacteric symptoms increased in intensity in all groups; patients receiving T had less increase in hot flashes (p= 0.004) and vaginal dryness (p= 0.03). There were no significant differences between groups in mood changes (anxiety and depression), general loss in strength, cardiac complaints, sleep disorders, nervousness, joint/muscle symptoms, or loss of libido. Conclusions: Combination treatment with G/E is not more toxic than standard treatment with G alone. The addition of T reduces the severity of some of the climacteric symptoms due to treatment and also may reduce bone loss. No significant financial relationships to disclose.
Oxaliplatin, 5-FU, and leucovorin (FOLFOX) in advanced biliary tract cancer.
Authors: S. Lee, K. H. Kim, H. J. Kim, S. H. Kim, S. B. Bae, C. K. Kim, N. Lee, K. T. Lee, S. K. Park, S. H. Park, J. Won, J. H. Moon, D. S. Hong, H. S. Park
Journal: Journal of Clinical Oncology (2011)

4106 Background: There is no standard palliative chemotherapy regimen in biliary tract cancers (BTC). Fluoropyrimidine or gemcitabine, with or without platinum, are most frequently used. The purpose of this prospective multicenter phase II study was to evaluate the efficacy and safety of FOLFOX-6(5-FU/LV plus oxaliplatin) combination chemotherapy in patients with advanced BTC. Methods: Eligible criteria included pathologically or cytologically confirmed biliary adenocarcinoma, unresectable or metastatic BTCs with at least one measurable lesion, no previous palliative chemotherapy, age ≥ 18, performance status ≤ 2, adequate organ function and no clinically significant cardiovascular disease. 89.8% patients had metastatic disease. All patients received FOLFOX-6 (oxaliplatin 85mg/m2 and folinic acid 400 mg/m2 on day 1 follwed by a 5-FU bolus 400 mg/m2 and 46-h infusion 2400 mg/m2 every 2 weeks) until progression of disease or unacceptable toxicities. Tumor response was evaluated each after four treatment cycles using the RECIST. Results: 49 patients were enrolled in this phase II study from May 2008 to Aug 2010. Medain age was 60.14 years (range 35-80), male/female=27/12, ECOG performance status 0/1/2 = 23/21/5. The primary tumor site was 14 patients in gallbladders, 28 patients in intrahepatic cholangiocarcinoma, and 7 patients in extrahepatic cholangiocarcinoma. 44 patients showed metastatic disease at baseline. Total chemotherapeutic cycles were 210 and 4.29 cycles were performed each person. Treatment related grade 3/4 toxicities included (number of cycles) diarrhea (2), neutropenia (10), neutropenic fever (2), anemia (1), thrombocytopenia (2), nausea (1) and pneumonia (1). Overall response rate was 16.3% and overall disease control rate was 61.7%. The median TTP was 3.83 months (95%CI, 3.45-5.68 months) and the overall survival was 10.77 months (95%CI, 7.92-13.62 months). No treatment related deaths occurred during the study. Conclusions: This results suggest that FOLFOX-6 would be an effective and well-tolerated chemotherapy regimen for Korean patients with advanced BTC.
Effect of race on the safety and efficacy of pemetrexed (P) therapy in locally advanced and metastatic non-small cell lung cancer (NSCLC)
Authors: D. F. Tai, P. Kulkarni, Y. Wang, J. Gill, C. Obasaju
Journal: Journal of Clinical Oncology (2007)

18082 Background: P is a multitargeted antifolate active in NSCLC. While a number of clinical trials have evaluated P safety and efficacy in general patient populations, little is known of the possible impact of race on the utility of P therapy in NSCLC. The objective of this post-hoc analysis was to evaluate the effect of race on the safety and efficacy of P (single-agent or in combination) in patients with locally advanced and metastatic NSCLC. Methods: Data from 6 trials with at least 5% non-Caucasian patients were pooled for analyses. One Phase III trial evaluated P in a second-line setting. All other trials used P in Phase II first-line settings. Patients were given at least one dose of P (single-agent or in combination) at 600 mg/m 2 (59 patients) or 500 mg/m 2 (469 patients) every 21 days. Demographic, safety, and efficacy data were stratified broadly by race, to either Caucasian or non-Caucasian groups. Kaplan-Meier method was used to estimate median survival. The Cox model was used to calculate the hazard ratio (HR) for survival, adjusting for significant prognostic factors, including disease stage, performance status, gender, and line of treatment. Results: Results are summarized in the data table below. The adjusted HR for survival (non-Caucasian versus Caucasian) was 0.89 (p=0.365). Conclusions: In this post-hoc analysis of results from clinical trials using P therapy in NSCLC, race did not have a statistically significant impact on response rate, disease control rate, or survival. However, P therapy appeared to be better tolerated by non-Caucasian patients. [Table: see text] No significant financial relationships to disclose.
Randomized phase III trial of imatinib (IM) rechallenge versus placebo in patients (pts) with metastatic and/or unresectable gastrointestinal stromal tumor (GIST) after failure of at least both IM and sunitinib (SU): Right study.
Authors: Yoon-Koo Kang, Min-Hee Ryu, Baek-Yeol Ryoo, Hyun Jin Kim, Jong Jin Lee, Changhoon Yoo, Byung-Ho Nam, Nikhil Ramaiya, Jyothi Priya Jagannathan, George D. Demetri
Journal: Journal of Clinical Oncology (2013)

LBA10502 The full, final text of this abstract will be available at abstract.asco.org at 7:30 AM (EDT) on Monday, June, 3, 2013, and in the Annual Meeting Proceedings online supplement to the June 20, 2013, issue of Journal of Clinical Oncology. Onsite at the Meeting, this abstract will be printed in the Monday edition of ASCO Daily News.
Psychotherapy of severe depression
Authors: S Arieti
Journal: American Journal of Psychiatry (1977)

The author discusses his clinical experiences in treating severly depressed patients with psychotherapy. The psychotically depressed person cannot use normal mechanisms to recuperate from sadness because he is prevented from doing so by a preexisting life ideology that may include living for a dominant other or a dominant goal and that restricts his vision of alternative approaches to living. The therapist treating the severely depressed must initially assume a strong role; later, he helps the patient recognize depressive cognitive patterns and guides and motivates him to try other ways of living.
Prospective validation of a risk model for first cycle neutropenic complications in patients receiving cancer chemotherapy
Authors: G. H. Lyman, N. M. Kuderer, J. Crawford, D. A. Wolff, E. Culakova, M. S. Poniewierski
Journal: Journal of Clinical Oncology (2006)

8561 Background: A nationwide, prospective cohort study was undertaken to develop and validate a risk model for neutropenic complications (NC) in cancer patients receiving chemotherapy. Methods: 3,596 patients initiating a new chemotherapy regimen with solid tumors or lymphoma were registered at 115 randomly selected sites. Data on at least 1 cycle of chemotherapy were available on 3,468. A logistic regression model for cycle 1 NC was derived and then validated using a split sample random selection process. Results: The risk of cycle 1 NC ranged from 5.5%-30.2%, averaging 18.5% across tumor types. No significant differences in distribution of NC or predictive factors were observed between the derivation dataset (n=2,592) or the validation dataset (n=876). Major independent baseline clinical risk factors for cycle 1 NC in the derivation model include: prior chemotherapy (P=.044), number of myelosuppressive agents (P&lt;.0001), anthracycline-based regimens (P&lt;.0001), planned delivery &gt;85% of standard (P&lt;.0001), cancer type (P&lt;.0001), concurrent antibiotics (P=.023) or phenothiazines (P=.006), abnormal alkaline phosphatase (P=.002), elevated bilirubin (P=.031), low platelets (P=.004), elevated glucose (P=.023) and reduced glomerular filtration rate (P=.013). Reduced risk of cycle 1 NC was associated with primary prophylaxis with a myeloid growth factor (P&lt;.0001). Model R 2 was 0.273 and c-statistic 0.80 [95% CI: 0.78–0.82; P&lt;.0001]. At the median predicted risk of cycle 1 NC of 11%, model test performance consisted of: sensitivity 84%; specificity 57% and diagnostic odds ratio (DOR) 7.2 while cycle 1 NC risk was 31% and 6% among high risk and low risk half, respectively. The model performed well in the smaller validation dataset with a model R 2 of 0.354 and c-statistic of 0.84 [95% CI: 0.81–0.87, P&lt;.0001]. Test performance of the model in the validation sample included: sensitivity 90%; specificity 62%; DOR 14.1 and risks of 35% and 4% in high risk and low risk patients, respectively. Conclusions: Validation in a randomly selected patient sample suggests that this model has general applicability in identifying patients at increased risk for NC. Further validation in other independent cancer patient populations receiving chemotherapy is planned. [Table: see text]
Validation of a 16-gene signature for prediction of recurrence after nephrectomy in stage I-III clear cell renal cell carcinoma (ccRCC).
Authors: Bernard J. Escudier, Serge Koscielny, Margarita Lopatin, Christer Svedman, Virginie Verkarre, Camelia Radulescu, Yann Neuzillet, Isabelle Hemmerlé, Marc Olivier Timsit, Athanasios C. Tsiatis, Michael Bonham, Dejan Knezevic, Thierry Lebret, Audrey D. Goddard, Mejean Arnaud
Journal: Journal of Clinical Oncology (2014)

4502 Background: New molecular diagnostics are needed to improve assessment of recurrence risk after nephrectomy in ccRCC. The 16-gene (11 cancer-related, 5 reference) Recurrence Score (RS) was previously developed in a cohort of 931 stage I-III ccRCC patients (pts) from Cleveland Clinic, requiring validation in an independent study. Methods: A prospective clinical validation study of the Oncotype DX RS in stage I-III ccRCC pts treated with nephrectomy from 1995 to 2007 was conducted by a French consortium. Genes, algorithm, endpoints, methods, and analysis plan were pre-specified and locked prior to merging clinical and molecular data. Gene expression was quantitated by RT-PCR in fixed paraffin-embedded primary ccRCC tissue without knowledge of pt clinical characteristics or outcomes. Recurrence-free interval (RFI, primary endpoint), renal cancer-specific survival (RCSS), disease-free survival (DFS) and overall survival (OS) were analyzed using Cox PH regression stratified by stage with data censored at 5 years, and Kaplan-Meier methods. Results: RT-PCR was successful in 626/645 pts (97%): 398 stage I, 54 stage II, 174 stage III. Median follow up was 5.5 yrs. 5-yr recurrence risk was dependent upon stage (7%, 16% and 30% in stage I, II and III). Continuous RS predicted recurrence risk (HR per 25 point increase in RS (HR/25) = 3.9, 95% CI 2.6-5.8, p<0.001). RS predicted RCSS, DFS and OS (all with p<0.001). In multivariable analyses, RS continued to predict recurrence (HR/25 =2.7, 95% CI 1.6-4.5, p<.001) after adjustment for tumor size, Fuhrman grade and necrosis. RS identified 39% of stage I pts with an average 5-yr recurrence risk of 2% (95% CI 0-7%) and 15% of pts with a 23% (95% CI 13-39%) risk. In stages II-III, RS identified 19% of pts with a 2% (95% CI 0-16%) and 44% of pts with a 39% (95% CI 29-50%) recurrence risk. Conclusions: The 16-gene Oncotype DX RS is validated as a predictor of clinical outcome in pts with stage I-III ccRCC and provides significant information beyond conventional clinical and pathologic characteristics. The RS may be useful to select patients for adjuvant treatment trials, for active surveillance of small renal masses, and for surveillance strategies after surgery.
Circulating tumor cells: Multimarker gene profile for tailoring chemotherapeutical response in adeno carcinomas.
Authors: N. Fersis, I. Kubisch, D. Ernst, A. de Albuquerque, S. Kaul, G. Stamminger, U. Stoelzel, A. Teubner
Journal: Journal of Clinical Oncology (2010)

10638 Background: In this experimental work we present a new immunomagnetic technique by the introduction of 2 antibodies (BM7 and VU1D9) for tumor cell selection and the use of a multimarker panel for identification of circulating tumor cells in peripheral blood of patients with adenocarcinomas. Methods: The high affinity antibodies BM7 (MUC1) and VU1D9 (EpCAM) were used for immunomagnetic tumor cell enrichment from 10mL samples of peripheral EDTA-blood of metastatic breast cancer patients and local advanced or/and metastatic gastrointestinal cancer patients. Separated cells were lysed and used for mRNA isolation and c-DNA synthesis. A real-time quantitative RT-PCR approach for the markers cytokeratin 19 and 20 (CK19 and CK20), mammaglobin 1 (MG1), CEA, epithelial cell adhesion molecule (EpCAM), aldehyde dehydrogenase 1 (ALDH1), Survivin, HER-2, immunosupressive CD276, chemokine receptor 4 (CXCR4), hypoxia inducible factor (HIF-1alpha) and metastasis associated in colon cancer (MACC) were used for tumor cell identification. Results: Sensitivity of the marker panel was validated in calibration tests with 2 cells and 10 cultured tumor cells and specificity was confirmed by examination of blood from healthy donors. Positivity rate of local advanced and/or metastatic gastrointestinal cancer patients was 73.5%, while 67.7% of metastatic breast cancer patients showed multimarker positivity. The marker with the highest expression level in metastatic breast cancer patients was CK19 followed by EpCAM. In local advanced and/or metastatic gastrointestinal cancer patients the most frequent identified genes were EpCAM, Survivin and CEA. Patients responding to therapy were characterized by immediate erradication of circulating tumor cells. Conclusions: The optimized surrogate marker panel linked to apoptosis, invasion, angiogenesis and stem cell phenotype should improve early detection of metastasis as well as monitoring of therapy response and selection of tailored therapy regimes. Circulating tumor cells expressing the newly introduced markers Sur, MACC and HIF-1alpha are clearly associated with aggressive tumor behaviour and poor clinical outcome. No significant financial relationships to disclose.
Effect of <i>BRAF<sup>V600E</sup></i> on response to sorafenib in advanced thyroid cancer patients
Authors: M. S. Brose, A. B. Troxel, M. Redlinger, K. Harlacker, C. Redlinger, A. A. Chalian, K. T. Flaherty, L. A. Loevner, S. J. Mandel, P. J. O'Dwyer
Journal: Journal of Clinical Oncology (2009)

6002 Background: We are conducting an open-label phase II study of sorafenib in patients with metastatic, iodine-refractory thyroid carcinoma. Methods: 55 Patients were administered sorafenib 400 mg orally BID. Responses were monitored by PET and CT. Primary endpoints were response rate (RR) and progression free survival (PFS) by RECIST criteria. BRAF and RAS mutation status is determined by DNA sequencing. Outcome data is evaluated using the Kaplan-Meier method and log-rank test. Biologic activity in tissue obtained during treatment at response and progression is being explored using immunohistochemistry (IHC) to pERK, pAKT and Ki-67 among others, in pretreatment blocks from virtually all patients, and a subset of 14 patients in whom on-treatment tissue is available. Results: We have completed accrual of the 55 patients planned for enrollment; median time on study is 34 weeks and 25 pts (45%) are male. Histological subtypes include papillary (PTC): 25 pts (47%); follicular/Hürthle Cell (FTC): 19 pts (36%); medullary: 4 pts (8%), and poorly differentiated/anaplastic: 5 pts (9%). 52/55 patients are evaluable for response at this time. Median PFS was 84 wks. Genotyping of BRAF is complete in 16 patients. For patients with PTC/FTC, the PFS for those with BRAF wt was 54 wks compared to 84+ wks for patients with BRAF V600E (p = 0.028). On-treatment tissue at progression demonstrates heterogeneity, with p-ERK and p-AKT suppressed in some areas, but highly expressed in others. Data at 6 months post accrual of the last patient will be presented along with patient thyroglobulin levels, PET and CT scans. IHC and additional genotyping will also be presented. Conclusions: Sorafenib has activity in patients with advanced thyroid cancer with an overall PFS of 84 wks. While most patients with PTC or FTC achieve durable responses, patients whose tumors harbor BRAF V600E have significantly longer PFS than those that are BRAF wt . [Table: see text]