tbuckley/cabot-search huggingface dataset:
Long-term complications of platinum in testicular cancer survivors
Authors: J. H. Oh, D. D. Baum, J. Ensor, S. Pham, M. D. Muddiman, S. Nguyen, I. Chen
Journal: Journal of Clinical Oncology (2006)

4589 Background: Long-term medical complications of platinum have become a major priority in the care of testicular cancer survivors. This study aimed to describe the prevalence of these complications from platinum-based therapy in American testicular cancer survivors. Methods: Testicular cancer survivors with no evidence of disease for at least 2 years were interviewed, had lab tests, and charts reviewed. Demographics, comorbidities, blood pressure, treatment, and outcomes were compared between all treatment modalities. NHANES 2002 and NHIS 2004 were used to obtain national estimates. Results: The mean age was 41 years; 72.7 % had nonseminoma, 96.5% had orchiectomy, 21.0% received radiation (XRT), and 82.5% platinum. The mean follow-up was 8.4 years. There was no statistical difference in the rates of Coronary Artery Disease (CAD), hyperlipidemia, hypertension (HTN), renal insufficiency (RI), or hypomagnesemia (see table ). There was a trend toward an increase in hyperlipidemia at follow-up compared to initial visit in all treatment groups but HTN increased only in those who did not receive platinum. Conclusion: Excluding HTN, we observed a trend toward an increase in the prevalence of RI, hypomagnesemia, hyperlipidemia, and CAD among patients who received platinum when compared to their baseline rates. Similar to a recent study by Huddart et al, we saw a trend toward higher risk of developing CAD in those who received both platinum and XRT. These findings suggest that hyperlipidemia and HTN may be more related to orchiectomy or the germ cell tumor itself than being a complication of platinum. Further prospective cohort studies with a larger group of survivors who have not received platinum are warranted to determine if HTN and hyperlipidemia are true complications of platinum-based chemotherapy. [Table: see text] No significant financial relationships to disclose.
A pilot study of adjuvant therapy in patients with cervical cancer at high risk of recurrence after radical hysterectomy and pelvic lymphadenectomy.
Authors: M S Wertheim, T B Hakes, A N Daghestani, D Nori, D H Smith, J L Lewis
Journal: Journal of Clinical Oncology (1985)

The prognosis after surgical therapy (radical hysterectomy and pelvic lymphadenectomy) of stages IB and IIA carcinoma of the cervix is affected by several histopathologic findings within the resected specimen. Patients at high risk of recurrence include those with involved pelvic lymph nodes, lymphatic or vascular invasion in the cervix, tumor size greater than 4 cm, grade 3 lesions, adenosquamous histology, parametrial invasion, and evidence of locally metastatic (noncontiguous) disease. We report the results of adjuvant chemotherapy (cisplatin and bleomycin) and pelvic radiotherapy in 32 patients with cervix cancer deemed to be at high risk of recurrence after radical hysterectomy and pelvic lymphadenectomy. The continuous disease-free survival rate for the 32 evaluable patients in 84% at a mean and median follow-up time of 28 months. Three patients are dead of disease and two patients are alive after treatment of local recurrences giving a survival rate of 91%. The two patients who are alive after disease recurrence demonstrated only locally recurrent disease while the three patients who have died with recurrent disease relapsed both locally and systemically. Complications of this treatment program were not significantly greater than those observed in prior studies using the combination of surgery and adjuvant radiotherapy without chemotherapy. When compared with the results from historical controls in a large series of similar patients at the same institution, the results in this pilot study are encouraging and would seem to justify a randomized prospective clinical trial.
Phase I trial of combination becatecarin and oxaliplatin in patients with advanced solid tumors
Authors: S. Manda, C. Mauser, J. Bokar, M. Cooney, J. Brell, S. Krishnamurthi, P. Savvides, P. Ivy, S. Remick, A. Dowlati
Journal: Journal of Clinical Oncology (2007)

2561 Background: Becatecarin (rebeccamycin analogue-RA) is an anti-tumor antibiotic with inhibitory activity against both topoisomerase II and I as well as DNA intercalating properties. We performed a phase I trial to a) determine the maximum tolerated dose (MTD) of RA in combination with oxaliplatin; b) determine the dose limiting toxicities (DLT) (c) obtain data on pharmacokinetics and (d) observe for any antitumor activity. Methods: Eligibility criteria included patients with advanced solid tumors refractory to standard therapy; performance status 0–2; adequate hematologic, renal and liver function. Patients were treated with RA as a 1 hour infusion daily x 5 and oxaliplatin on day 5 only, after RA infusion. Treatment was repeated q 21 days. The following dose levels were evaluated: Dose level 1: RA 80 mg/m 2 /d and oxaliplatin 90 mg/m 2 ; Dose level 2: RA 80 mg/m 2 /d and oxaliplatin 130 mg/m 2 ; Dose level 3: RA 110 mg/m 2 /d and oxaliplatin 130 mg/m 2 . Results: A total of 15 evaluable patients were enrolled. Median age was 56 (8 male, 7 female). A variety of tumor types were enrolled. A total of 56 cycles were administered. DLT occurred at a dose of RA at 110 mg/m 2 /d x 5 days and oxaliplatin at 130 mg/m 2 and consisted of grade 3 hypophosphatemia and grade 4 atrial fibrillation. At this dose level 2 of 3 enrolled patients also developed grade 3 neutropenia. The MTD and recommended phase II dose was RA at 80 mg/m 2 /daily x 5 along with oxaliplatin 130 mg/m 2 day 5 q 21 days. Three confirmed partial responses were observed in patients with hepatocellular, gallbladder and esophageal cancers. Six patients experienced stable disease. Conclusions: At the MTD combination RA and oxaliplatin is well tolerated and given the response rate and stable diseases observed, phase II studies are recommended. Supported by Grants U01 CA62502, MO1-RR-00080, K23 CA109348–01 from the National Institutes of Health. No significant financial relationships to disclose.
Association of expression of ERG oncoprotein with development of disease recurrence and prostate cancer-specific mortality.
Authors: Richard Johnston, Elysia Sophia Spencer, Xiaoyu Qu, Cigdem Himmetoglu Ussakli, Ryan Robert Gordon, Funda Vakar-Lopez, Daniel Lewinshtein, Jared Lucas, Albert Dobi, David G. Mcleod, Min Fang, Shiv Srivastava, Peter Nelson, Christopher R. Porter
Journal: Journal of Clinical Oncology (2012)

e15207 Background: ETS-Related Gene (ERG) protein is present in approximately half of prostate cancer (PCa) specimens and correlates with TMPRSS2-ERG rearrangement. ERG oncogenic activation is believed to be a causal genomic alteration in a significant portion of PCa, its prognostic value in disease progression remains uncertain. This study evaluated ERG levels at radical prostatectomy (RP) to determine if it was predictive of earlier relapse or prostate cancer-specific mortality (PCSM). Methods: From 1954-1997, 1004 consecutive patients underwent RP at Virginia Mason Medical Center in Seattle. Recurrence was confirmed by tissue diagnosis or radiographic signs. Death certificates confirmed PCSM. Patients without tissue were excluded. 34 patients with metastases or PCSM were matched to patients without recurrence at a 1:2 ratio. Paraffin embedded tissue was stained with two anti-ERG monoclonal antibodies, clone 9FY (Furustao et al., PCPD, 2010) and clone EPR3864 (Epitomics, Burlingame, CA). A pathologist evaluated the nuclear expression intensity using a 4-point scale. Statistical analysis was performed on SAS. Results: Mean follow up was 10.26 yrs.Antibody 9FY detected ERG in 10/16 (62.5%) PCSM and 24/44 (54.6%) no recurrence patients. Cancer expression intensity was higher from patients that developed recurrent disease, 0.99 vs 1.59 (p = 0.0265) and PCSM 2.09 (p = 0.0002). Antibody EPR3864 detected ERG in 11/17 (64.7%) PCSM and 26/48 (52.1%) no recurrence patients. Cancer expression intensity was higher from patients that developed recurrent disease, 0.97 vs 1.64 (p = 0.011) and PCSM, 2.30 (p &lt; 0.0001). The two antibodies were independent of PSA and grade and were highly correlated with each other (p &lt; 0.0001). Conclusions: ERG expression at time of surgery was prognostic for the development of disease recurrence and PCSM. Previous studies have shown an increased lifetime risk of PCSM with ERG expression in a surveillance cohort. This is the first report linking PCSM to ERG expression in men treated with surgery. ERG scoring may be a useful metric to identify patients who would benefit from adjuvant treatment or closer follow-up, allowing more accurate individual patient treatment plans.
Phase I evaluation of AZD2171, a highly potent, selective VEGFR signaling inhibitor, in combination with gefitinib, in patients with advanced tumors
Authors: H. Van Cruijsen, E. E. Voest, C. M. Van Herpen, K. Hoekman, P. O. Witteveen, M. L. Tjin-A-ton, C. J. Punt, T. Puchalski, T. Milenkova, G. Giaccone
Journal: Journal of Clinical Oncology (2006)

3017 Background: AZD2171 is an oral, highly potent, vascular endothelial growth factor (VEGF) signaling inhibitor. This Phase I trial is evaluating the safety, tolerability, pharmacokinetics (PK) and efficacy of AZD2171, in combination with gefitinib (IRESSA), an inhibitor of EGF receptor tyrosine kinase. Methods: Patients with advanced solid tumors refractory to standard therapies received once-daily, oral AZD2171 (20, 25, 30 or 45 mg) and gefitinib 250 (Part A1) or 500 mg (Part B1) until dose-limiting toxicity was observed. The potential PK interaction of AZD2171 30 mg with gefitinib 250 mg was studied in an expanded cohort (Part A2). Part B2 follows the design of Part A2, with a gefitinib dose of 500 mg. Results: As of September 1, 2005, 70 patients (22–78 years) have received treatment ( Table ). Overall, the most frequently reported adverse events (AEs) were diarrhea, anorexia, fatigue and hypertension (91%, 64%, 51% and 51% of patients; respectively), with evidence of an AZD2171-related dose response for hypertension (reported in 36%, 75%, 47% and 75% of patients at AZD2171 20, 25, 30 and 45 mg; respectively). These were also the most commonly reported CTC grade ≥3 AEs, occurring in &lt;13% of patients, in addition to increases in alanine aminotransferase (7%) and aspartate aminotransferase (4%). The steady-state PK parameters for AZD2171 (30 mg) and gefitinib (250 mg) are comparable with those seen previously with either agent alone. In total, 28 patients had a best RECIST response of stable disease (22 patients were non-evaluable). A patient with mesothelioma (45 mg AZD2171, Part A1) and a patient with renal cancer (20 mg AZD2171, Part B1) had confirmed partial responses. The second patient underwent surgery and is currently disease-free. Conclusions: No unexpected toxicities are associated with AZD2171 (20–45 mg) in combination with gefitinib (250 or 500 mg) and the preliminary response data are encouraging. [Table: see text] [Table: see text]
Anamorelin in patients with advanced non-small cell lung cancer and cachexia: Results from the phase III studies ROMANA 1 and 2.
Authors: Jennifer S. Temel, David Christopher Currow, Kenneth Fearon, Ying Yan, John Friend, Amy Pickar Abernethy
Journal: Journal of Clinical Oncology (2015)

175 Background: Cancer anorexia-cachexia syndrome is common in patients with non-small cell lung cancer (NSCLC). It is characterized by loss of lean body mass (LBM) and negatively impacts quality of life. Anamorelin HCl (ANAM) is a novel investigational ghrelin receptor agonist with anabolic and appetite-enhancing activity. Methods: Two randomized, double-blind, Phase 3 ROMANA 1 (N = 484; NCT01387269) and ROMANA2, (N = 495; NCT01387282) trials assessed ANAM (100 mg) efficacy/safety versus placebo in patients with unresectable stage III/IV NSCLC and cachexia ( ≥ 5% weight loss within prior 6 months or BMI &lt; 20 kg/m 2 ) over 12 weeks. Co-primary endpoints were change from baseline over 12 weeks in LBM and hand grip strength (HGS). Secondary endpoints included changes in body weight and in the anorexia-cachexia subdomain of the Functional Assessment of Anorexia/Cachexia Therapy questionnaire, and pooled survival from ROMANA 1 and 2. Exploratory post-hoc analyses determined change in total body and fat mass from baseline to 12 weeks. Results: Over 12 weeks ANAM significantly increased LBM vs placebo in ROMANA 1 (1.10 vs -0.44 kg, p &lt; 0.001) and ROMANA 2 (0.75 vs -0.96 kg, p &lt; 0.001); HGS was similar in the two arms. In both studies ANAM vs placebo increased body weight (2.20 vs 0.14 kg, p &lt; 0.001; and 0.95 vs -0.57 kg, p &lt; 0.001) and improved anorexia/cachexia symptoms (4.12 vs 1.92, p &lt; 0.001; and 3.48 vs 1.34, p = 0.002). Increases in total body mass (2.87 vs 0.07 kg, p &lt; 0.001; and 2.04 vs -0.59 kg, p &lt; 0.001) and in fat mass (1.21 vs -0.13 kg, p &lt; 0.001; and 0.77 vs 0.09 kg, p = 0.012) were observed for ANAM vs placebo. ANAM was well tolerated; the most frequent drug-related adverse event in ROMANA 1 and 2 was hyperglycemia (5.3% and 4.2%). There was no difference between study arms in median 1-year survival. Conclusions: In two global, Phase 3 studies, ANAM treatment for 12 weeks was well tolerated, and increased LBM, body weight, total body mass and fat mass indicating anabolic activity and suggesting restoration of energy balance in advanced NSCLC patients with cachexia. ANAM also improved anorexia-cachexia symptoms/concerns. Similar pooled survival was observed between the study arms. Clinical trial information: NCT01387269, NCT01387282.
Abstract P139: Insulin Resistance in Premenopausal Women with Type 1 Diabetes is Explained by Abdominal Obesity, Physical Inactivity and Altered Sex Hormones
Authors: Lindsey M Duca, Rachel M Sippl, Janet K Snell-Bergeon
Journal: Circulation (2014)

Women with type 1 diabetes (T1D) lose the premenopausal protection from cardiovascular disease (CVD) that non-diabetic (non-DM) women have compared to men, and are also more insulin resistant than non-DM women. Standard CVD risk factors have not been found to adequately predict CVD in the T1D population, but insulin resistance is emerging as a potentially important risk factor. The aim of this study was to determine whether sex hormone levels such as estradiol (E2), total testosterone (TT), and sex-hormone binding globulin (SHBG) explained any of the decreased insulin sensitivity in women with T1D, which could be important in CVD prevention. This study included 25 premenopausal women 18-45 years of age with a mean ± SD age of 33 ± 8 years who completed a three stage (4, 8 and 40 mU/m2/min) hyperinsulinemic-euglycemic clamp during the luteal phase of the menstrual cycle (T1D n=12 and non-DM n=13). A steady state was achieved during the last 30 minutes of the high insulin infusion stage and mean glucose infusion rate (GIR [mg/kg/FFM/min]) during this time was used as an estimate of the skeletal muscle glucose disposal rate. Sex hormones were compared using unpaired Student t tests between T1D and non-DM participants during each phase of the menstrual cycle and during the morning of the clamp.. Significant differences were explored in multivariable linear regression in which stepwise model selection was used to determine the final model adjusting for age and diabetes status. In age-adjusted analysis, women with T1D were less than half as insulin sensitive as non-DM women (least squares mean ± SE: 7.5±2.2 vs. 19.0±2.1, respectively, p=0.0014). SHBG was significantly higher in the T1D than the non-DM subjects the morning of the clamp (p&lt;0.0001) and during each phase of the menstrual cycle (p = 0.01). TT was significantly higher in T1D women during the early follicular phase of the menstrual cycle (p=0.02) and was negatively correlated with GIR (r = -0.54, p = 0.04). E2 during the early follicular phase was positively correlated with GIR (r = 0.83, p = 0.01). In multivariable analysis, the difference in the GIR was attenuated by 58%(1-(5.1/12.14)) (least squares mean ± SE: 10.9 ± 1.7 in T1D vs. 16.0 ± 1.5 in non-DM, p = 0.07) after adjusting for age, diabetes status, minutes of vigorous activity, average waist circumference, free estradiol index and testosterone during the early follicular phase of the menstrual cycle In conclusion, the decreased insulin sensitivity observed in premenopausal T1D women with regular menstrual cycles can be mostly explained by lower levels of physical activity, greater central adiposity and differences in sex hormone levels. Most of these factors are modifiable, and so could be important targets in the reduction of CVD.
Preoperative renal parenchymal volumetrics and prediction of renal insufficiency following radical nephrectomy.
Authors: Deepak Kumar Pruthi, Sasha Oomah, Ruchi Chhibba, Ian Kirkpatrick, Thomas McGregor
Journal: Journal of Clinical Oncology (2015)

471 Background: To identify predictors of post-operative renal insufficiency by analyzing pre-operative imaging volumetrics among patients undergoing radical nephrectomy (RN) for renal cell carcinoma (RCC). Methods: A retrospective review of all patients undergoing RN for RCC between January 2011 and August 2013 was performed. Estimated glomerular filtration rate (eGFR) was calculated employing the modified diet in renal disease (MDRD) formula using the pre-operative and one-year serum creatinine values. Pre-operative and 1-year post-operative CT/MRI scans were reviewed. AW Volume Share 5 workstations were utilized to calculate volumes. Statistical analysis using Chi-square and Fisher exact test were employed. Results: Of the 147 patients undergoing RN 65 patients met the inclusion criteria. Patients with smaller tumor volumes (&lt;375 cm 3 ) were more likely to have a greater decline in their post-operative eGFRs (&gt;35%) when compared to patients with larger tumors (58 vs. 21%; p=0.0165). Patients with a pre-operative eGFR &gt;60 ml/min/1.73m 2 had a greater (&gt;25%) drop in their 1-year eGFR (81 vs. 47%; p=0.0084). A smaller volume (&lt;150 cm 3 ) of parenchyma of the ipsilateral kidney was associated less compensatory (&lt;25%) hypertrophy (100 vs. 69, p=0.0348). Smaller tumors (&lt;300 cm 3 ) were more likely to have a greater degree (&gt;10%) of compensatory hypertrophy (78 vs. 43% p=0.0234) and less blood loss (&lt;300 cc, 82 vs. 44%, p=0.0082). Older patients and patients with a combined history of diabetes (DM) and hypertension (HTN) were more likely to have compensatory (&gt;25%) hypertrophy (age &gt;65, 100% vs. 31%, p&lt;0.001; DM+HTN, 100% vs. 75%, p=0.0084). The degree of compensatory hypertrophy (&gt;25%) however, did not predict 1-year eGFR (35%) change (p=0.2203). New kidney disease (eGFR&lt;60 ml/min/1.73m 2 ) occurred in 71% patients. Conclusions: Volumetric imaging shows promising potential and may become a valuable tool in predicting post-operative renal insufficiency for patients undergoing nephrectomy and should be investigated further both in RN and partial nephrectomy cohorts.
Enzastaurin in patients with follicular lymphoma: Results of a phase II study.
Authors: L. Schwartzberg, R. C. Hermann, I. W. Flinn, D. B. Flora, J. Song, O. Hamid, B. K. Lin, M. H. Dreyling
Journal: Journal of Clinical Oncology (2010)

8040 Background: Protein kinase C beta (PKCb) has a pivotal role in normal B-cell signaling and survival. Overexpression of PKCb is implicated in the pathogenesis of follicular lymphoma (FL). Enzastaurin (ENZ), an oral serine/threonine kinase inhibitor, targets the PKCβ and PI3K/AKT pathways to inhibit tumor cell proliferation, induce apoptosis, and suppress tumor-induced angiogenesis. Methods: This is an open-label, single-arm, phase II study of patients (pts) with histologically confirmed grade 1 or 2 and stage III or IV measurable FL. Pts either were chemonaive or had relapsed after one chemotherapy regimen or single-agent rituximab (completed ≥ 6 months before enrollment). Pts received 500 mg oral ENZ, once daily (1125-mg loading dose on D1) up to 3 yrs or until progression, withdrawal, or unacceptable toxicity occurred. The primary endpoint was response rate (RR). Other objectives included duration of response (DoR) and safety. Results: A total of 66 pts (22 males and 44 females), a median age of 62 yrs (range, 33-82) were enrolled. According to the Follicular Lymphoma International Prognostic Index score, 12% had low-risk disease (0-1 risk factors), 53% intermediate-risk disease (2), and 35% high-risk disease (3-5). Forty-six pts (70%) were chemonaive and 20 pts (30%) had one prior chemotherapy (including rituximab). To date, the median overall exposure is 10.1 months (range, 1-26.6 months). Of 64 pts who received at least one dose of ENZ for efficacy analyses, 1 (1.6%) had a complete response, 15 (23.4%) had partial response, for an overall RR of 25%, and 25 (39.1%) had progressive disease. The median DoR has not been reached (range, 59-687 days; 11 pts in remission). Thirty-seven pts (56%) discontinued treatment, 3 (4.5%) due to adverse events, of which 2 (3%) were possibly drug-related: bronchitis and skin rash. Three pts (4.5%) had drug-related serious adverse events: grade 3 bronchitis, grade 2 diarrhea, and grade 2 pancreatitis. There were no drug-related deaths. Twenty-nine pts (44%) continue receiving treatment. Conclusions: Preliminary results indicate that ENZ has clinical activity and is well tolerated in pts with grade 1 or 2 FL. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Lilly Lilly Lilly
Abstract 747: Normal Values of Left Ventricular Parameters in Elite Athletes by 3D Echocardiography
Authors: Stefano Caselli, Riccardo Di Pietro, Fernando M Di Paolo, Cataldo Pisicchio, Filippo M Quattrini, Maria L Foschi, Michela Pagliaro, Elvira De Blasiis, Antonio Pelliccia
Journal: Circulation (2009)
Can we Predict Severe Adverse Events (Saes) and Clarify Unfit Populations for Platinum-Based Chemotherapy in Elderly Patients (Over 70 Years of Age) with Advanced Non-Small Cell Lung Cancer (Nsclc)? (Cjlsg 1203 Trial)
Authors: T. Kato, M. Morise, M. Ando, E. Kojima, T. Ogasawara, R. Suzuki, J. Shindoh, M. Matsumoto, Y. Sugino, M. Ogawa, Y. Nozaki, M. Kondo, H. Saito, Y. Hasegawa
Journal: Annals of Oncology (2014)