tbuckley/cabot-search huggingface dataset:
Ten Years Experience of a Genetic Eye Clinic: 1978–1987
Authors: S Bundey, S J Crews
Journal: Journal of the Royal Society of Medicine (1989)

Over a ten year period of running a joint ophthalmological/genetic clinic, 387 index patients were advised, and a further 260 individuals (relatives of the above) were examined and counselled. Determination of the precise diagnoses and modes of inheritance in the index patients necessitated retinal function tests in 267 (69%) and examination of 84 of their parents and 23 sisters and daughters. Finally, 41% of index patients and 39% of their relatives were given high risks for transmitting an autosomal dominant or X-linked disorder to their children. It is noteworthy that 16% of these high-risk index patients and 66% of these high-risk relatives had no visual symptoms; ophthalmological expertise was required to assess the significance of their minor signs. It was concluded that an active Register is required for contacting relatives outside the nuclear family, and for future recall of children currently too young for carrier tests or genetic counselling.
Positron emission tomography as a tool for early prediction of therapy outcome in patients with soft tissue sarcoma
Authors: B. Kasper, S. Dietrich, A. Dimitrakopoulou-Strauss, A. D. Ho, G. Egerer
Journal: Journal of Clinical Oncology (2008)

10572 Background: We used 2-deoxy-2-[18F]fluoro-D-glucose (FDG) positron emission tomography (PET) to evaluate the FDG uptake in patients with soft tissue sarcoma (STS). Treatment effect was assessed with regard to prediction of therapy outcome. Methods: The evaluation includes 27 patients with high risk STS receiving chemotherapy consisting of doxorubicin 75 mg/m2/day 1 and ifosfamide 1,500 mg/m2/day 1–4 (AI-G regimen) or etoposide 125 mg/m2/day 1+4, ifosfamide 1,500 mg/m2/day 1–4 and doxorubicin 50 mg/m2/day 1 (EIA regimen). Patients were examined using PET prior to onset of therapy and after completion of the first cycle of AI-G and after two cycles of EIA chemotherapy, respectively. Restaging according to RECIST criteria using computed tomography and magnetic resonance tomography was performed after six cycles of AI-G or four cycles of EIA chemotherapy and served for reference. Results: Clinical outcome of 27 evaluable patients was as follows: two patients with no evidence of disease, seven with partial remission, 14 with stable disease, and four patients with progressive disease. Median average standard uptake value (SUV) prior to onset of chemotherapy was 3.5 [range: 0 - 27.9] in comparison to 2.4 [range: 0 - 9.9] after chemotherapy treatment. Median SUVmax was 11.5 [range: 0 - 44.7] prior to chemotherapy in comparison to 7.9 [range: 0 - 21.7] following therapy. A significant difference of the progression-free survival for patients with a decrease in SUV (responders) in comparison to patients with an increase or stable SUV (non-responders) could be demonstrated (p = 0.0187). Conclusions: On the basis of these data, PET can be used as an easily measurable tool for early prediction of chemosensitivity of the tumor and moreover of the therapy outcome. Moreover, PET may even complement the existing RECIST criteria for tumor response evaluation. No significant financial relationships to disclose.
Primary malignant sarcomas of the heart and great vessels - a single center experience
Authors: K. Oechsle, H. Aebert, R. Teichmann, W. Budach, L. Kanz, G. Ziemer, J. T. Hartmann
Journal: Journal of Clinical Oncology (2004)

9044 Background: Sarcomas of the heart and the great vessels are very rare entities. The most common subtypes included leiomyo- and angiosarcoma. Prognosis is very poor because of locally advanced or metastatic stage at diagnosis. Methods: Between 6/2001 and 10/2003 12 patients (pts) have been identified in the sarcoma registry of Tuebingen University. Results: Median age was 43 years (22 –72). All pts were symptomatic with reduction of vitality, anorexia, dyspnoea, or neurological symptoms at the time of reception. Tumors were located in atrium [(n=5), left (3)/right (2)], Art. pulmonalis (n=3), Aorta (n=2), pericardium or left chamber, (n=1 each). Six pts presented with localized disease and 5 pts underwent curative intended resection (n=1 considered as irresectable). Six pts had advanced disease including brain mets (4 pts), lymph nodes involvement (2), lung (3) and liver mets (2). Five of these 6 pts underwent palliative resection to relieve the physiologic effects of the tumor. Three out of 5 pts with curative intended surgery have subsequently developed recurrence within 6, 8 and 25 mos despite adjuvant treatment. Palliative chemotherapy including adriamycin and ifosfamide has been applied in 7 pts and 4 pts attained some response to treatment (n=1 PR, n=3 SD). Palliative radiation included 3 pts with brain metastases and a single pt with progressive primary tumor. After a median follow up 13 mos (2 –28) 2 pts had NED, 3 pts are alive with disease and 7 pts have died due to tumor progression. Conclusions: Pts with primary sarcomas of the heart and the great vessels were often of young age, and half of them presented with locally or distant advanced disease. These pts should preferentially be referred to a tertiary Cancer Center immediately after diagnosis without preceding treatment attempts. Although the majority of pts cannot be treated curatively due to the delay in diagnosis, an optimized treatment approach including neoadjuvant chemo-/radiotherapy might enhanced the rate of complete resection depending on the histological subtype and responsiveness to treatment. No significant financial relationships to disclose.
Appropriate schedule of oral tegafur / uracil (UFT) in combination with irinotecan (CPT-11) and bolus 5-FU / <i>l</i>-leucovorin (LV) in patients (pts) with metastatic colorectal cancer (MCRC): A phase I study
Authors: N. Chayahara, T. Tamura, I. Miki, T. Okuno, T. Kamigaki, H. Nishisaki, Y. Inoue, T. Maeda, T. Sakaeda, T. Azuma
Journal: Journal of Clinical Oncology (2007)

14538 Background: FOLFIRI is one of the standard regimens for MCRC. Considering the burden of continuous 5-FU administration, oral fluoropyrimidine-based therapy has been proposed in several clinical trials; however, gastrointestinal toxicity makes it difficult to perform successive oral chemotherapy. Therefore, no previous study could confirm whether to replace FOLFIRI with oral regimen. In order to find an appropriate schedule of oral fluoropyrimidine with safety and efficacy instead of continuous infusion of 5-FU, clinical trial using CPT-11, bolus 5-FU / l-LV and oral UFT / LV was conducted in pts with MCRC. Methods: Pts with MCRC, age &gt; 18 years, ECOG PS 0–2, adequate organ function, and no or 1 prior chemotherapy were eligible. Pts received CPT-11 (100mg/m 2 ) / 5-FU (500mg/m 2 ) / l-LV (15mg/m 2 ) i.v. on day 1 and UFT (300mg/m 2 ) / LV (75mg/body) p.o. on days 1–5 (level 1), days 1–7 (level 2), or days 1–10 (level 3). Each course was repeated every 14 days. After determining feasible UFT / LV schedule, CPT-11 was dose-escalated (level 4: 125 mg/m 2 ; level 5: 150mg/m 2 ). Results: Nineteen pts were enrolled. A dose-limiting toxicity (DLT) of grade 4 neutropenia lasting for &gt; 4 days was observed in 1 pt at level 2. Additional 3 pts at this level showed no toxicity of grade 3 or 4. A DLT of treatment delay (&gt;8 days) was observed in 1 pt at level 3 because of prolonged neutropenia. Other 2 pts at level 3 refused to continue treatment within 4 cycles because of prolonged grade 2 anorexia. Obvious difference in toxicity was observed between level 2 and level 3. Therefore, 7-day-administration of UFT / LV was recommended. No DLT was observed at level 4 and 5, and the recommended dose of CPT-11 was 150mg/m 2 . The overall response rate was 66.7%. The median time to disease progression was 8.0 months. Conclusions: This oral fluoropyrimidine-based regimen is considered feasible and effective. The treatment schedule of UFT might be a key to prevent an early dropout due to gastrointestinal toxicity. Further study will be needed to confirm toxicity and efficacy of this regimen compared to FOLFIRI profile. No significant financial relationships to disclose.
Non small cell lung cancer (NSCLC): Are elderly patients being under-treated?
Authors: R. Ng, R. De Boer, A. Park, S. Knight, I. Glaspole, M. Chao, S. Wong, M. Green
Journal: Journal of Clinical Oncology (2004)

7118 Background: With an aging population, the number of elderly patients (≥70 years old) presenting with NSCLC is increasing. Several trials have indicated that elderly patients respond well to standard therapies. Nevertheless, there is a concern this group may not be receiving adequate therapy. The aim of this review was to investigate if this was true for our institution. Method: We reviewed the database of all patients presenting with NSCLC to Western Hospital from 1997–2002. Patients were separated into <70 and ≥70 years old, and examined by disease stage and initial therapy. Results: 412 patients with NSCLC were identified. 364 were assessable for stage and treatment (see table). 198 were <70 years and 166 were ≥70. It appears that for all stages of disease, elderly patients were less likely to receive treatment. This is demonstrated in 2 critical patient groups: curable stage I/II disease with 16/54 (30%) elderly patients undergoing curative surgery compared to 43/59 (73%) younger patients (p<0.001); and locally advanced disease with 14/60 (23%) elderly patients undergoing combined chemo/radiotherapy/surgery compared to 38/78 (49%) younger patients (p=0.004). Conversely, patients not receiving any treatment was significantly higher in the older group (62/166 [37%] compared to 26/198 [13%], p<0.001). Conclusions: The data indicates that elderly patients with NSCLC are less likely to receive active therapy at any stage of disease. Possible reasons may include physician bias, poor performance status, co-morbidities and patient choice. As recent reports have suggested that all patient groups with NSCLC can benefit from surgery, chemotherapy and combined modality treatment, it is critical to ensure that the reason for lack of active treatment of elderly patients is not age alone. No significant financial relationships to disclose.
Abstract 13960: Dietary Iron Restriction Prevents and Rescues Renal Injury in a Rat Model of Chronic Kidney Disease
Authors: Aya Fujii, Yoshiro Naito, Hisashi Sawada, Shinichi Hirotani, Toshihiro Iwasaku, Akiyo Eguchi, Yoshitaka Okuhara, Kojiro Miki, Mitsumasa Ohyanagi, Takeshi Tsujino, Tohru Masuyama
Journal: Circulation (2012)

Background: Iron accumulation is associated with the pathogenesis of cardiovascular disease and chronic kidney disease (CKD). However, little is known about the effects of iron restriction against these diseases. Here, we investigated the effects of dietary iron restriction on hypertension and renal injury in a rat model of CKD. Methods and Results: CKD was induced by 5/6 nephrectomy in Sprague-Dawley rats. After operation, 5/6 nephrectomized rats were given iron-restricted diet from 1 day to 16 week for prevention protocol or from 8 week to 16 week for rescue protocol. Other CKD rats were given a normal diet. Sham-operative rats given a normal diet served as a control. CKD rats developed hypertension, proteinuria, glomerulosclerosis, podocyte injury, and tubular dilatation. In contrast, dietary iron restriction prevented the development of hypertension and kidney injury after 16 weeks diet. Iron restriction suppressed vascular hypertrophy, fibrosis, and inflammation in CKD rats. The phosphorylation of Ak...
The impact of shortened vitamin supplementation lead-in time before pemetrexed (P) in patients with relapsed small cell lung cancer (SCLC)
Authors: D. A. Richards, M. Socinski, R. N. Raju, K. Coke, C. Reynolds, R. Chen, J. L. Cunneen, D. F. Tai, J. A. Treat, C. K. Obasaju
Journal: Journal of Clinical Oncology (2007)

7726 Background: Clinical studies of P have shown less overall toxicity and reductions in Grades 3–4 hematologic and nonhematologic toxicities when pts are pretreated with folic acid and vitamin B 12. Current recommendations are to give folic acid 350 μg - 1,000 μg by mouth for at least 5 of 7 days prior to the 1st dose of P, and 1 injection of vitamin B 12 1000 μg during the week preceding the 1st P dose. Treatment delay to allow this supplementation may be clinically undesirable, particularly in pts with aggressive malignancies. A trial evaluating single-agent P for the treatment of relapsed SCLC gave us opportunity to observe the effects of a shortened lead-in time for vitamin supplementation. Methods: We reviewed data from a U.S. trial designed to assess the safety and efficacy of single-agent P in chemosensitive and chemorefractory relapsed SCLC pts. Eligible pts had limited or extensive-stage SCLC, PS 0 to 2, and 1 prior chemo regimen. Pts received P doses of 500 mg/m 2 or 900 mg/m 2 q 21 d. The protocol required the administration of folic acid for at least 5 of 7 days prior to the 1st P dose, and vitamin B 12 administration on Day 1, Cycle 1, or up to 14 days prior to the 1st P dose. Included in the analysis were pts who received at least 1 dose of folic acid prior to 1st P dose. We then analyzed preliminary toxicity results for pts receiving vitamin B 12 for 0–3, 4–6 and =7 days prior to 1st P dose. Results: From 7/2004 to 3/2006, 116 pts were treated with P. At baseline M/F 57%/59%; median age 64.5 years (range 35–85); PS 0/1/2 was 39%/57%/20%. Cycle 1 vitamin administration timing data is available for 109 pts. Data for all 116 pts will be reported at time of meeting. Because toxicities observed between the 2 P doses were not significantly different, the combined toxicities for both dosing groups are reported here. Conclusions: Based on this data, Vitamin B 12 given less than 7 days prior to P does not appear to be associated with increased serious toxicities. No significant financial relationships to disclose. [Table: see text]
A phase I study of brivanib alaninate (BMS-582664), an oral dual inhibitor of VEGFR and FGFR tyrosine kinases, in combination with full dose cetuximab (BC) in patients (pts) with advanced gastrointestinal malignancies (AGM) who failed prior therapy
Authors: C. R. Garrett, L. L. Siu, A. B. El-Khoueiry, J. Buter, C. M. Rocha-Lima, J. L. Marshall, G. Kollia, L. Velasquez, S. Syed, D. Feltquate
Journal: Journal of Clinical Oncology (2008)

4111 Background: Brivanib alaninate (B) is an oral prodrug of BMS-540215, a dual tyrosine kinase inhibitor of VEGFR and FGFR signaling. Prior studies have validated both VEGF and EGF signaling pathways as targets in AGM. The MTD of B is 800 mg qd (ASCO #3051, 2006). Methods: An open-label phase I dose-escalation study of B in combination with cetuximab (C) was conducted in pts with AGM who failed prior therapy. B was given po Day 1 and qd from Day 8, starting at 320 mg. C was given IV Day 8 (400 mg/m2) then weekly (250 mg/m2). Dose escalation of B continued to 800 mg qd, when an expansion cohort for pts with colorectal cancer (CRC) was opened for additional safety and efficacy. Fresh tissue and blood sampling for biomarker and PK analysis was acquired. FDG-PET was obtained at baseline x 2, and Days 15 and 56. Tumor response (modified WHO) was evaluated q 8 weeks. Results: 60 pts (57 CRC, 2 esophageal, and 1 hepatocellular carcinoma) were treated with B 320, 600 or 800 mg qd in combination with C for a median 8.3 weeks (range 0.1–57.3+). A single DLT, bilateral pulmonary emboli, occurred at 320 mg. B+C was tolerable with few G3/4 AEs (fatigue 16%, transaminitis 12%, diarrhea 2%). PK was linear up to 800 mg. There was no apparent effect of C or B on each drug’s PK. FDG-PET results from 48 pts with 1–3 target lesions showed baseline reproducibility for SUVmax, SUVpeak and SUVmean, with intrasubject CV of 15%, 16% and 20%, respectively. There was a dose-dependent decline in plasma COL IV and sVEGFR2 levels at Day 36 compared with baseline (COL IV: 320 mg, 26%, 800 mg 41%; sVEGFR2: 320 mg, 1.5%, 800 mg 31%). Best responses in subsets of 34 evaluable CRC pts treated with B 800 mg + C are shown in the Table. Conclusions: B ≤800 mg qd + C was tolerable and had clinical activity in pts with advanced CRC. Pretreatment FDG-PET is a reproducible imaging modality. Prior therapy EGF inhibitor - - + + VEGF inhibitor - + - + Evaluable pts (total) 12 12 1 9 34 PR 4 1 0 0 5 (15%) SD 5 7 1 6 19 (56%) PD 3 4 0 3 10 (30%) PR + SD ≥ 6 mo 4 3 0 3 10 (30%) Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration Bristol-Myers Squibb Bristol-Myers Squibb
Impact of surgical care on survival in esophageal cancer.
Authors: Chase Campbell, Joshua S. Hill, Danielle Boselli, Jonathan C. Salo
Journal: Journal of Clinical Oncology (2015)

142 Background: Survival after multimodality treatment of localized esophageal cancer depends upon complex interactions between the patient, tumor biology, and treatment factors. The National Cancer Database (NCDB) was used to analyze prognostic factors to identify areas for treament optimization. Methods: 8,072 patients with localized esophageal cancer treated with neoadjuvant therapy undergoing surgical resection between 2004 and 2006 were identified from the NCDB. Covariates were analyzed for association with survival using univariate and multivariate Cox models. Results: A multiviariate Cox proportional hazards model was constructed, with the following significant factors predictive of survival. (See Table.) Survival varied markedly based upon the annual surgical volume of esophageal resection performed at the hospital. For hospitals performing 5 or fewer esophageal resections per year (15% of cases), 5-year survival was 40.0%, compared with 48.6% for hospitals performing 20 or greater (26% of cases). Hospital length of stay after surgery also profoundly affected survival. For patients with a post-operative length of stay of less than 14 days, 5-year survival was 40% and median survival 39.1 months. Median survival was 28 months, 19 months, and 15 months in patients with a hospital length of stay of 14-21 days, 21-28 days, and greater than 28 days, respectively. Conclusions: Data from the NCDB confirms the association between perioperative events and long-term survival after resection for esophageal cancer. Given the wide variance in outcomes based upon perioperative treatment factors, future improvements in outcomes are unlikely to be dramatically influenced by optimization of chemotherapy and radiation therapy. Improvement in outcomes of the treatment of esophageal cancer will likely require understanding how the perioperative period influences long-term survival, which should drive priorities for research and treatment improvement. [Table: see text]
First-in-human study evaluating safety and pharmacokinetics of endoxifen, a potent estrogen-receptor antagonist for breast cancer.
Authors: A. Ahmad, S. Shahabuddin, S. Sheikh, P. Kale, M. K, R. C. Rane, I. Ahmad
Journal: Journal of Clinical Oncology (2010)

3087 Background: Endoxifen is an active metabolite of tamoxifen, a widely used breast cancer drug. Treatment of breast cancer directly with endoxifen may eliminate tamoxifen metabolism associated variability and avoid a potential serious drug-drug interaction. In this study, the safety, tolerability, and pharmacokinetics (PK) of endoxifen at escalating single doses were assessed in healthy, adult, male and female human subjects. Methods: An open label, single oral dose, randomized, dose escalating parallel study was conducted in 40 healthy male and female fasting subjects. Eight subjects received a single dose of 0.5, 1, 2, or 4 mg endoxifen tablets. Tamoxifen (Nolvadex) 20 mg tablets were administered to eight subjects as reference. Blood samples were collected at predose and up to 528 hours postdose for PK. Results: Single oral dose of endoxifen at 0.5, 1, 2, or 4 mg was safe and well tolerated. Adverse events were not found and no clinically significant changes in laboratory or other safety variables were noted. Endoxifen displays near dose-proportional pharmacokinetics, and small deviations from dose. The drug at all doses was rapidly absorbed with Tmax 6±2.9 h and half-life (t3/4) of 54.9±8.6. Increase in Cmax and AUC appeared proportional to dose when consecutive dose increments were compared. Endoxifen administered at 0.5, 1, 2, or 4 mg resulted in 1.36, 3.8, 5.5, and 14.5 ng/mL Cmax and 99.1, 231, 330, 763 ng.h/mL AUC0-inf, respectively. When compared with endoxifen levels in 20 mg tamoxifen administered subjects, 0.5, 1, 2, and 4 mg endoxifen showed 228%, 804%, and 1,216%, 3,385% higher Cmax, respectively, while Tmax was significantly lower in endoxifen treated subjects. Conclusions: This is the first ever report on human trial demonstrating escalating single oral dose of endoxifen. The results indicated that oral administration of endoxifen is safe and systemically bioavailable in healthy adult human subjects and exhibited linear pharmacokinetics over the dose range of 0.5-4 mg. The drug continues in clinical development as a potentially new therapeutic agent in patients with breast cancer. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Intas Pharmaceuticals, Jina Pharmaceuticals, Lambda Therapeutic Research Ltd
Intermittent chemotherapy (ICh) for metastatic castration-resistant prostate cancer (mCRPC): Results of a prospective randomized phase II trial of the DoD Prostate Cancer Clinical Trials Consortium.
Authors: A. L. Harzstark, T. M. Beer, V. K. Weinberg, C. S. Higano, L. T. Nordquist, J. E. Rosenberg, J. J. Alumkal, E. Y. Yu, J. Mi, E. J. Small
Journal: Journal of Clinical Oncology (2011)

133 Background: Docetaxel remains the standard of care for patients (pts) with mCRPC. However, the optimal duration of chemotherapy (Ch) is not known. Providing Ch holidays is often undertaken, but is not well characterized. A randomized phase II trial was undertaken to test two ICh regimens. Methods: Pts with Ch naive mCRPC and KPS &gt; 60% were eligible. Pts were treated with “induction” docetaxel 75 mg/m 2 q3 weeks, and prednisone 5 mg po bid. After 6 cycles, responding pts (PSAWG1 criteria) stopped Ch and were randomized to observation (Obs) or to GM-CSF, 250 mcg/m 2 sq daily for 14 days out of every 28 day cycle. Pts were followed with monthly PSA and imaging every 2 cycles until progressive disease (PD) by PSAWG1 criteria, at which point they resumed treatment with Ch, again for 6 cycles, followed by the same “off Ch” regimen. The primary endpoint was the time to PD while on Ch (time to Ch resistance.) Results: Of 97enrolled pts to date, 94 are evaluable (3 are still undergoing induction). 69 pts completed induction (25 did not due to PD, adverse events (AE), or MD choice), of which 27 had PD after 6 cycles. Thus, 42/94 evaluable pts (45%) were eligible for randomization. Of these, 21 pts underwent Obs and 21 received GM-CSF. To date, 23/42 (55%) pts who underwent a Ch holiday restarted Ch, all for PSA PD. 8/23 (35%) had a response to Ch re-initiation. (15 pts did not re-start Ch because of AE, other therapy being started, or patient choice, and 4 pts are still undergoing either Obs or GM-CSF.) Obs pts were “off Ch” for a median of 2 months (range 2-4), compared with 3 months (range 2-8) for GM-CSF pts. Conclusions: While feasible, only 45% of pts met criteria for ICh. 35% of pts responded to Ch re-initiation. Insufficient data exist to assess the impact of GM-CSF on time off Ch or time to Ch resistance. No significant financial relationships to disclose.