tbuckley/cabot-search huggingface dataset:
Circulating molecular markers in predicting radiation-induced lung damage
Authors: L. Zhao, F. Kong, J. Hayman, G. Kalemkarian, D. Arenberg, S. Lysons, J. Curtis, K. Cease, D. Brenner, T. Lawrence
Journal: Journal of Clinical Oncology (2006)

7144 Background: We hypothesized that circulating molecular markers such as transforming growth factor-beta1 (TGF-β1), interleukin-6 (IL-6), and angiotensin-converting enzyme (ACE) change early during the course of radiotherapy (RT), and that such changes precede RILD after completion of the therapy. Methods and Materials: Patients with stage I-III NSCLC treated with RT (11) or chemoRT (15) (enrolled onto two prospective clinical trials) were included in this study. Serum and platelet poor plasma were obtained prior to (Pre-RT), at 40–50 Gy (during-RT), and at the end of RT (end-RT). The plasma TGF-β1 and IL-6 and serum ACE levels were measured using molecule specific enzyme-linked immunosorbent assays. The endpoints for RILD were ≥ grade 2 radiation pneumonitis (RP) and measures of pulmonary function tests such as forced vital capacity (FVC), forced expiratory volume in the 1st second (FEV1), and diffusing capacity for carbon monoxide (DLCO). The minimal follow-up duration was 3 months. Data is presented as mean ± standard deviation; student t-test was used for significant analysis. Results: Plasma TGF-β1 and IL-6 levels changed remarkably after 40–50 Gy of RT. The mean relative TGF-β1 levels (during-RT over pre-RT) were 1.9 ± 0.9 and 0.9 ± 0.6 in patients with and without RP (p = 0.010), respectively. There were no significant associations between changes of plasma IL-6 and ACE levels and the occurrence of RP. Significant DLCO reduction was observed at 3 months after RT in almost every patient, and such reduction was significantly more remarkable in those who had radiation induced elevation in plasma IL-6 levels (34.8 ± 15.9% versus 15.6 ± 14.5%, p = 0.045). Interestingly, the pre-RT ACE level was significantly associated with changes of FEV1 (p = 0.037) and FVC (p = 0.014): improvement of 13.2 ± 12.0% and 11.0 ± 9.0% versus reduction of 7.6 ± 17.0% and 10.8 ± 17.7% for patients with high versus low levels, respectively. Conclusion: Radiation induced elevation in circulating TGF-β1 and IL-6 levels may be predictive of RILD, while serum ACE level may be associated with decreased risk of RILD. No significant financial relationships to disclose.
Abstract 3670: Effects of Telmisartan, Angiotensin II Receptor Blocker, on Endothelial Function and Aortic Stiffness in Morning Hypertensive Patients with the Metabolic Syndrome and Obstructive Sleep Apnea
Authors: Hideki Watanabe, Kunio Nakagawa, Masaaki Kakihana
Journal: Circulation (2008)

Morning hypertension and the metabolic syndrome (MetS) are recognized as a risk factor for cardiovascular disease, and are reported to be associated with obstructive sleep apnea (OSA). Recently it has been reported that telmisartan has an action of PPAR - γ agonist. We assessed the effects of telmisartan on endothelial function and aortic stiffness in morning hypertensive patients with MetS and OSA. Thirty untreated morning hypertensive patients with MetS and mild or moderate OSA (an apnea-hypopnea index [AHI] 5 – 30) were randomized to receive telmisartan (Telmisartan group, 20 - 40 mg/day, n=15) or amlodipine (Amlodipine group, 2.5 - 5 mg/day, n=15). Flow-mediated dilatation (FMD) and nitroglycerin-induced dilatation (NID) of brachial artery were measured by using ultrasound system. Pulse wave velocity (PWV) was measured by using oscilometric technique. We assessed insulin resistance by HOMA-IR, and measured high sensitivity C-reactive peptide (hsCRP) and thiobarbituric acid reactive substance (TBARS) a...
Relationship of time to relapse (TTR) and survival post relapse (SPR): Exploration of risk factors from the first annual follow-up data set of randomized pbo-controlled study of oregovomab (OV) as a consolidation therapy of patients with advanced ovarian cancer (OC)
Authors: J. S. Berek, P. Taylor, B. Schultes, J. Balser, C. F. Nicodemus
Journal: Journal of Clinical Oncology (2004)

5069 Background: OV is a MAb specific for CA125 being studied as an immunotherapeutic in OC. A recently reported randomized phase II study utilized TTR as a primary endpoint as a surrogate of survival. The study identified a favorable subpopulation (SFLT) that appeared to benefit from OV antibody stimulated immune activation (Proc ASCO 2003 #660). A long-term follow-up program to survey long term outcomes is in progress. Results of the first annual follow-up survey have been analyzed to address the relationship between TTR and SPR. As SPR varies between patients, factors that predict SPR are highly relevant to individualized patient management strategy following front-line therapy. Intervention with cytotoxic, cytostatic, immune modifying, or combination therapies must satisfy a rigorous analysis of risk benefit to be recommended. The ability to extrapolate TTR data to survival is dependent on an appreciation of factors that influence SPR. Results: 145 OC patients were entered into follow-up, with 67 defined as SFLT. 30 patients are currently censored for both TTR and survival, and excluded from initial analysis. For the overall analysis set (n=115) median TTR was 8.7 mo [7.2–10.4] and median SPR was 21.4 mo [18.9–27.9]. Survival was censored in 46.1%. Risk factors significantly associated with both relapse and survival in Cox modeling, were not associated with SPR. Cox modeling identified CA125 value at time of relapse as a possible explanatory factor associated with SPR. 43 of 67 in the SFLT population are censored for survival making further assessment of this population premature at this time. Conclusions: Standard risk factors associated with TTR and survival are not associated with SPR. CA125 at relapse, however, is a possible explanatory factor. Information from this ongoing long-term follow up will be critical to the definitive analysis in terms of TTR and survival of the two phase III IMPACT studies currently recruiting SFLT patients for consolidation immunotherapy post-standard front-line therapy. Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration AltaRex Corp.; Unither Pharmaceuticals, Inc.
A phase II of high dose capecitabine plus irinotecan for patients with advanced or metastatic gastric cancer: preliminary results
Authors: S. Oh, H. Seo, H. Sung, I. Choi, S. Kim, S. Kim, J. Seo, B. Kim, S. Shin, Y. Kim, J. Kim
Journal: Journal of Clinical Oncology (2006)

14086 Background: Capecitabine is the prodrug of 5-FU to generate maximal tumor activity in tumor site and/or improve the tolerability, has demonstrated the synergistic activity with irinotecan in some solid cancers . Previous study showed the dose intensification of capecitabine increased the response rate with comparable toxicities in metastatic colorectal cancer. We conducted this study to ascertain the efficacy and toxicity of irinotecan and high dose capecitabine combination chemotherapy for chemotherapy-naïve advanced or metastatic gastric cancer. Methods: Patients who were advanced or metastatic gastric cancer and have not received any chemotherapeutic drug except adjuvant chemotherapy, received irinotecan 130mg/m 2 intravenously (i.v) for 90 min on day 1 and day 15 and capecitabine 3500 mg/day, divided two, was administered for 7 consecutive days from day1 and day 15, and this was followed by a 7-day drug-free interval. Results: 35 eligible patients were enrolled in this study from Nov/2003 to Nov/2006. 14 women and 21 men: median age 51 ys, range 27–81. A total 106 courses were administered, and median number of courses per patient was three (range, 1–8). Intent-to-treatment analysis showed the one complete response (2.9%), 13 partial responses (37.1%), 9 stable disease (25.7%), 8 progressive disease (22.9%) and 4 non-evaluable patients (11.4%). The overall response rate was 40% (95% CI: 23.5–56.5). Grade 3–4 toxicities were: neutropenia 8 (22.8%), nausea/vomiting 2 (5.7%), stomatitis 1 (2.9%), ischemic colitis 1 (2.9%), anemia 3 (8.6%), diarrhea 2 (5.7%), alopecia 3 (8.6%). Treatment related death was shown at one patient due to pneumonia. Dose intensity of irinotecan and capecitabine was 94% and 93%, respectively. Median time to progression was 4 months (range, 0.5 - 11 months), median survival duration was 8.5 months (range, 0.5 - 45 months), and median response duration was 2.5 months (range, 0.5 - 9 months). Conclusions: We suggest that irinotecan and high dose capecitabine combination chemotherapy is the tolerable regimen to advanced or metastastic gastric cancer with promising activity. No significant financial relationships to disclose.
Evaluation of the antitumor activity of sunitinib malate (SM) in solitary fibrous tumor (SFT)
Authors: P. G. Casali, S. Stacchiotti, E. Palassini, A. Marrari, T. Negri, C. Morosi, A. Messina, U. Pastorino, A. Gronchi, S. Pilotti
Journal: Journal of Clinical Oncology (2009)

10571 Background: SFT is a rare soft tissue tumor, with an unpredictable metastatic potential. When medical therapy is needed, cytotoxic chemotherapy is poorly active in this sarcoma subtype, but the activity of bevacizumab + temozolomide was recently reported. We explored the activity of SM in SFT, given the vascular pattern of this tumor and our preliminary observations about RTK activation (with upregulation of the PDGFR family, VEGFR and EGFR). Methods: From April 2008, 5 patients with progressive metastatic SFT resistant to conventional chemotherapy (male/female: 3/2 - mean-age: 58 years - PS: 0–3 - site: peritoneum 3, pleura 1, bladder 1) have been treated with continuous-dosing SM 37.5 mg/day, on an individual use basis. All patients were evaluated for response at least once, while 2 more patients are now starting therapy. RTK biochemical analysis was performed in 3 patients of this series, in addition to a group of other patients with malignant SFT whose cryopreserved material was available. Results: Between 3 weeks and 3 months, 4 in 5 patients had a tumor response according to Choi's criteria (all with RECIST stable disease) . The other patient stopped therapy for progression after 3 weeks and died 2 weeks later. Baseline PET was negative in 4 out of 5 patients. One responsive patient stopped therapy after 3 weeks for side effects and depression. The remaining 3 responsive patients are currently on treatment, although one had a focal progression after 9 months. In two, surgery of residual disease is planned, and downstream RTK signaling analysis will be performed on the specimen. Conclusions: SM has antitumor activity in SFT. This might help address an unmet clinical need in a rare sarcoma subtype. Biomolecular assessments are ongoing. [Table: see text]
Tricyclic Antidepressants
Authors: Jan Koch-Weser, Leo E. Hollister
Journal: New England Journal of Medicine (1978)

(Second of Two Parts)A curious paradox in present-day psychiatric practice is that patients with depression are often treated with little sense of urgency, whereas those with schizophrenia are treated aggressively, sometimes being overtreated. Patients with depression are likely to have their real problems compounded by a prolonged absence from work or family. On the other hand, most of those with schizophrenia have neither to worry about.One should attempt to alleviate depression as rapidly as possible, bearing in mind both the consequences of prolonged morbidity as well as the personal suffering of the depressed patient. The illness also has . . .
Phase II study of weekly docetaxel plus cisplatin as first-line therapy in advanced or metastatic non-small cell lung cancer (CHN TAX-206)
Authors: D. Chu, J. Li, X. Zhang, J. Liu, Z. Chen, Y. Lin, Y. Wang
Journal: Journal of Clinical Oncology (2007)

18173 Background: There has been increasing interest in the use of weekly administration of docetaxel as a way of reducing its hemotologic toxicity. Weekly docetaxel plus cisplatin has also shown promising efficacy and well tolerability for first-line treatment of advanced or metastatic NSCLC in our previous phase I study (2002 ASCO, abstract No 2744). We conducted this phase II trial to further evaluate this regimen’s efficacy and toxicity. Methods: Patients with histologically confirmed stage IIIB or IV NSCLC were treated with docetaxel (35 mg/m 2 , 30 min. iv. infusion) on days 1, 8, 15 and cisplatin (75 mg/m 2 , 30 min. iv. infusion) on day 1 repeated every 4 weeks for up to 6 cycles. Pts received oral dexamethasone 7.5 mg twice daily from the day before chemotherapy and consecutive two days thereafter. The primary endpoint of this phase II study is efficacy of the regimen. Results: A total of 83 patients were enrolled from July 2002 to June 2004, 75 patients were evaluable for response and 83 for safety. Median age was 55 years (range 29–70 years); and 69.9% were male; adenocarcinoma/squamous cell carcinoma/others (65/12/6); stage IIIB /IV( 47/36); ECOG PS 0/1(52/31). Median number of chemotherapy cycles was 3(1–5). One CR (complete response) and 22 PR (partial response) were achieved with an ORR of 30.7% in the evaluable patients. The 1-year survival was 48.6% with a median survival of 10.7 months (range: 3–34 months). Neutropenia was the most common adverse event, though most were mild; Grade III/IV toxicities per patient were: Neutropenia (15.6%), asthenia (11%), skin/nail toxicity (10.8%) and vomiting (9.6%). Febrile neutropenia was not observed. Conclusions: In the present study, the combination of weekly administration docetaxel combining with cisplatin appears well tolerated with very low frequency of severe hematologic toxicity and similarly efficacious as 3-weekly docetaxel in NSCLC pts. No significant financial relationships to disclose.
Pathologic predictors of <i>BRCA1/ BRCA2</i> (<i>B1/B2</i>) mutations in African-American (AA) women with early-onset breast cancer (BC)
Authors: S. M. Domchek, M. S. Simon, C. Hughes Halbert, T. R. Rebbeck, K. L. Nathanson
Journal: Journal of Clinical Oncology (2007)

10549 Background: African-American (AA) women more frequently have “triple negative” (ER-, PR-, HER2-) breast cancer (BC) and such BC are more frequently associated with B1 mutations; however, the correlation of triple negative BC in the AA population and B1/2 mutations is not known. We were interested in examining the prevalence of B1/2 mutations in a cohort of AA with early-onset breast as well as the associated pathologic characteristics. Methods: 85 unselected AA women diagnosed with 88 BC at or prior to age 40 were enrolled on study and underwent BRCA1/2 genetic testing by full sequencing at Myriad Genetics following informed consent. MLPA screening for large genomic rearrangements also was performed. Pathology reports were obtained and examined. Results: Of the 85 women, 16 (19%) had either a B1 (11) or B2 (5) deleterious mutation, which were associated with 19 BC. 19/85 (22%) women had a variant of unknown significance (VUS); 3 had B1 VUS, 15 had B2 VUS (including 2 with B1 mutations) and 1 had both B1 and B2 VUS. No mutations were detected with MLPA. Of the 14 BC in 11 B1 mutation carriers, 12 were ER- (86%), 13 were PR- (93%) and 3/12 were HER2+ (25%). Of the 5 BC in B2 carriers, 4 were ER- (80%), 1/4 HER2+ (25%). Receptor status was available in 77 of 88 cases (88%). Overall 41 of 77 (53%) cancers were ER-. 15 of 40 women (38%) with any ER- BC had either a B1 (11) or B2 (4) mutation. In contrast, of the 36 ER+ BC, 2 had a B1 and one had a B2 mutation (8%) (p=0.01). Both B1 carriers with ER+ BC also had a contralateral ER- BC. 18 of 65 (27%) cancers were known to be HER2+, of which 4 of 18 (22%) were associated with B1 or B2 mutations (p=NS). Median age of first BC in B1/B2 mutation carriers was 32 vs. 37 in non-carriers. Conclusions: In unselected AA women with early onset BC, B1/2 mutations were common and predominantly found in association with ER- BC. B2 VUS were detected frequently. HER2 overexpression did not predict against B1/2 mutations. No significant financial relationships to disclose.
Combined modality treatment of cutaneous T cell lymphoma: results of a 6-year follow-up.
Authors: C F Winkler, E A Sausville, D C Ihde, A B Fischmann, G P Schechter, P P Kumar, J R Nibhanupdi, J D Minna, R W Makuch, J L Eddy
Journal: Journal of Clinical Oncology (1986)

Thirty-nine patients with cutaneous T cell lymphoma (CTCL; including mycosis fungoides or the Sezary syndrome) with no previous treatment other than topical therapy or oral corticosteroids, received total skin electron beam irradiation (TSEB) and either sequential or simultaneous systemic chemotherapy. Median follow-up, measured from the time of initiation of therapy to the time of analysis, is in excess of 6 years and extends to 100+ months. Thirteen patients with stage I disease (limited to skin with no adenopathy) received 3,000 rad total skin electron beam irradiation followed by three 2-week courses of daily intravenous (IV) mechlorethamine. Twenty-six patients with advanced disease (stage II-IV) received 2,400 rad of TSEB and simultaneous chemotherapy with two alternating three-drug regimens: vinblastine, doxorubicin, and bleomycin (VAB) alternating with cyclophosphamide, methotrexate, and prednisone (CMP) administered over 54 weeks. The overall response rate was 92% with 16 of 39 patients (41%) achieving a histologically documented complete response (CR). Stage I patients had a significantly increased CR rate (77%) compared with stage II-IV (P less than .01). The overall 6-year survival was 92% for stage I patients and 26% for stage II-IV patients (23%) (P less than .001). Among ten completely responding stage I patients, six remain alive and disease-free in excess of 72 months. The median disease-free survival is 26 months for completely responding stage II-IV patients (P = .04), but none are continuous disease-free survivors after protocol treatment. We conclude that combined modality treatment can be safely administered and produces prolonged disease-free survival in some stage I patients, but not in more advanced stage patients.
Paclitaxel, bleomycin, etoposid, and cisplatin (T-BEP) as initial treatment in poor prognostic germ cell tumors (GCT). A phase II study
Authors: J. Mardiak, T. Salek, Z. Sycova-Mila, J. Obertova, M. Reckova, M. Mego, I. Koza
Journal: Journal of Clinical Oncology (2005)

4679 Background: Using T-BEP deWitt (Int J Cancer, 1999) achieved complete response in 100% of 13 patients (pts) with intermediate- or poor-prognosis germ-cell cancer in first line treatment. We present our results in poor prognostic group of patients. Methods: 21 pts with III.C stage of germ-cell cancer received the T-BEP as initial therapy. Six pts had extragonadal GCT, 11 pts (52%) had liver metastasis and 16 pts (62%) had S3 disease. Median number of metastatic sites was 3 (range 1 - 5). Four to six cycles of T-BEP were given 21 days apart. Paclitaxel 175mg/m2 was administered by 3-hour infusion on day 1, by start of BEP. BEP comprised etoposide at dose 100mg/m2 on days 1–5. The administration of hemopoetic growth factors was not scheduled. Surgical resection of all radiographic residua was considered. Relative dose intensity of paclitaxel was 93% (range 16 - 100%). Results: Favorable response was achieved in 13 (62%) pts, 95% CI (41 - 83%). With median follow up of 18 months 2 pts (15%) have relapsed. Two year estimated overall survival is 84% and 2-year estimated event-free survival is 45%. Median time to treatment failure was 9,6 months, 95%CI (5,2 - 9,6 months). Myelosuppression was the major toxicity, Gr3–4 leukopenia was experienced by 53%, trombocytopenia by 11% and febrile neutropenia by 29% of courses. Three pts experienced G3–4 mucositis and diarrhea and 2 pts hepatotoxicity Gr3–4. One pts had severe mycotic pneumonia with need of assisted ventilation. There was one treatment related death due to septic shock. Conclusions: T-BEP with standard dose of paclitaxel is effective regimen for patients with poor prognostic GCT. However toxicity of this chemotherapy combination is substantial. No significant financial relationships to disclose.
Treatment of peritoneal carcinomatosis due to GI-tract cancer by intraperitoneal application of the trifunctional antibody catumaxomab (anti-EpcAM x anti-CD3): Results of a phase I/II trial
Authors: M. A. Stroehlein, F. Lordick, D. Ruettinger, U. Gruetzner, H. Menzel, K. Bartelheim, M. Jaeger, H. Lindhofer, K.-W. Jauch, C. Peschel, M. M. Heiss
Journal: Journal of Clinical Oncology (2005)

2529 Background: Peritoneal carcinomatosis (PC) from GI-tract cancer is associated with prognosis of 3–6 months. Since chemotherapy and surgical procedures showed only limited efficacy, there is no standard therapy recommended. The trifunctional antibody (trAb) catumaxomab (anti-EpCAM x anti-CD3, removab) represents a new class of intact antibodies, which are able to re-direct T-lymphocytes to tumor cells and to induce active anti tumor immunity by activating FcγRI/III+ APC/DC by their intact Fc region. In a phase I/II trial, intraperitoneal application of catumaxomab was investigated in patients with PC due to GI-tract cancer. Methods: 17 patients (mean age 55 years; 7 gastric-ca, 9 colon-ca, 1 CUP) were included after diagnosis of EpCAM+ PC. Treatment consisted of 4 escalating doses of catumaxomab within 10 days by i.p. application. MTD was defined separately for the 1st, 2nd, 3rd and 4th infusion according to a dynamic escalation schedule. Anti-tumor efficacy was evaluated by immunohistochemical analysis of peritoneal lavages before and after treatment. Patients were free to get any further chemo- or radiotherapy after trAb treatment and followed up every 6 weeks. Results: I.p. application of catumaxomab was well tolerated. MTD was defined at 10 - 20 - 50 - 200 μg for the 1st, 2nd, 3rd and 4th i.p. infusion. Most frequent adverse events > CTC grade 2 were nausea/vomiting (14), abdominal pain (12), fever (6), exanthema (4), elevation of liver enzymes (4) and cholangitis (2), which could all be successfully treated by conventional medication. Analysis of the peritoneal lavages showed a significant decrease/complete destruction of tumor cells after trAb treatment in 7/8 patients. Presently, after a follow-up period of 10 months, 11/17 patients (64.7%) are still alive. These data will be updated at presentation. Conclusions: I.p. application of the trifunctional antibody catumaxomab is safe and technically feasible and may represent a new concept for treatment of PC due to gastrointestinal malignancies. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Fresenius Biotech, TRION Fresenius Biotech, TRION TRION Fresenius Biotech
Exploration de signes d'appel coliques par coloscanner à l'eau et recto-sigmodoscopie
Authors: ME Ciocirlan, M Ciocirlan, PJ Valette, JY Scoazec, JA Chayvialle, F Pilleul
Journal: Endoscopy (2006)

Le coloscanner à l'eau prend une place croissante dans la recherche de néoformations coliques. Sa valeur prédictive est actuellement en cours d'évaluation par rapport à la coloscopie. L'intérêt potentiel du couplage coloscanner-rectosigmodoscopie a ici hté évalué de façon prospective chez des patients présentant des symptômes autres que rectorragie ou melaena.