tbuckley/cabot-search huggingface dataset:
Unexpected excessive toxicity in a pilot study of accelerated conformal radiotherapy with concurrent chemotherapy for stage III NSCLC
Authors: M. Machtay, C. Washam, P. Devine
Journal: Journal of Clinical Oncology (2004)

7254 Background: The purpose of this study was to determine the safety and feasibility of a new accelerated chemoradiotherapy regimen consisting of hypofractionated concomitant boost radiotherapy and concurrent carboplatin/paclitaxel for locally advanced stage III non-small cell lung carcinoma (NSCLC). Methods: Radiotherapy (XRT) consisted of 60 Gy continuous course, over 4–4.5 weeks, via 3-dimensional conformal techniques. Once-daily treatments were used, but the large field (including gross tumor and selected elective nodal beds) was given a daily dose of 2–2.2 Gy, with a 0.8–1 Gy concomitant boost (field within a field) to the gross tumor. Weekly carboplatin (AUC=2) and paclitaxel (50 mg/m2) were given during XRT; then two cycles of systemic-dose carboplatin (AUC=6) and paclitaxel (100 mg/m2, 3 weeks out of 4) were planned. Additionally, the nutritional supplement glutamine (10 mg tid) was prescribed in an effort to decrease esophagitis and weight loss. Results: Before the early closure of this study due to toxicity, five patients were enrolled, of whom four are evaluable for feasibility/toxicity (one patient becamse very noncompliant shortly after enrollment and was found to have progression including brain metastases prompting hospice care). Acutely, no patient had Grade 3+ nonhematologic toxicity during concurrent chemo-XRT. However, hematologic toxicity was significant in the post-XRT consolidation phase, resulting in systemic chemotherapy dose reduction and/or discontinuation in 3 of 4 patients. Two patients experienced dose-limiting non-hematologic late chemoradiation toxicity. This included one (Grade 4) tracheoesophageal fistula which probably contributed to the patient's death and one Grade 3–4 radiation pneumonopathy. Two patients are dead of disease. Three patients are alive without definite evidence of disease at 14, 20 and 21 months followup. Conclusions: Despite the use of 3-D conformal technology, this regimen of concomitant boost accelerated hypofractionated radiotherapy with concurrent and systemic chemotherapy was excessively toxic and not feasible. Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Bristol-Myers Squibb Bristol-Myers Squibb Bristol-Myers Squibb
心サルコイドーシス患者における後期ガドリニウム増強(LGE)分布の特徴的なパターン-特発性拡張型心筋症との比較
Authors: Sano Makoto, Satoh Hiroshi, Shiraki Katsunori, Saotome Masao, Urushida Tsuyoshi, Katoh Hideki, Hayashi Hideharu
Journal: Circulation (2012)
Donepezil for cancer-related fatigue: A double-blind, randomized, placebo-controlled study
Authors: E. Bruera, B. El Osta, V. Valero, L. Driver, J. Palmer, B. Pei, L. Shen, V. Poulter
Journal: Journal of Clinical Oncology (2007)

9003 Background: Fatigue is the most frequent symptom in advanced cancer. No standard treatment is available. We previously found that open-label donepezil significantly improved fatigue by day 3 and 7 in patients (pts) on opioids for cancer pain (Fisch et al, ASCO 2003). The purpose of this study was to compare donepezil (D) with placebo (P) for fatigue in pts with advanced cancer. Methods: In this randomized, double-blind, placebo-controlled trial, pts with fatigue score = 4 on a 0 to 10 scale (10 = worst fatigue) for &gt; 1 week, hemoglobin = 10g/dl for = 4 weeks, and no major contraindication to D were randomized to receive D 5 mg or P orally every morning for 7 days. All pts were offered open-label D during week 2. Assessment included: research nurse daily phone call for fatigue and toxicity evaluation, Edmonton Symptom Assessment System (ESAS), Functional Assessment for Chronic Illness Therapy-Fatigue (FACIT-F), Sleeping Pattern Assessment, and overall effectiveness of the treatment. The FACIT-F fatigue subscale score on day 8 was considered the primary endpoint. Results: 103 pts were evaluable for final analysis. Mean difference in scores for symptoms intensity between baseline and day 8 are shown in Table 1 . FACIT-F fatigue subscale score at day 8 decreased a mean of 6 (10.6 SD) in the D arm (p &lt; 0.001) and 7.2 (9.5 SD) in the P arm (p &lt; 0.001). There was no significant difference in fatigue improvement between both arms according to the FACIT-F subscale (p = 0.57) and ESAS fatigue (p = 0.18) scores, and no significant difference in sleep quality score between D and P. On day 15 of the open-label phase, mean fatigue intensity remained significantly improved as compared to baseline on FACIT-F fatigue subscale (p &lt; 0.001) and ESAS fatigue (p &lt; 0.001) scores. No significant toxicities were observed. Conclusions: Both donepezil and placebo resulted in significant fatigue improvement. Donepezil was not significantly superior to placebo after one week. Our pilot findings are probably due to placebo effect. No significant financial relationships to disclose. [Table: see text]
The Advanced Renal Cell Carcinoma Sorafenib (ARCCS) expanded access trial: Subset analysis of patients (pts) with brain metastases (BM)
Authors: C. A. Henderson, R. M. Bukowski, W. M. Stadler, J. P. Dutcher, T. Kindwall-Keller, S. J. Hotte, K. Logie, B. Baltz, K. Wilson, R. A. Figlin
Journal: Journal of Clinical Oncology (2007)

15506 Background: Sorafenib (SOR) was demonstrated to be safe and effective in a phase III trial of previously treated RCC pts; however, pts with BM were excluded. BM occur in 5–10% of RCC pts, and generally portend a poor prognosis. Safety and efficacy of SOR in this pt population was therefore explored in a subset analysis of ARCCS, a community-based expanded access program. Methods: Pts received SOR 400 mg bid in this open-label, nonrandomized trial if they were =15 years old with advanced RCC and had ECOG PS of 0–2. Pts with BM were included but required to have some prior local therapy for their brain lesions. Prior treatment did not have to be successful, and pts whose BM had been surgically removed were also eligible for this protocol. BM were excluded as target lesions for RECIST unless they were the only lesions being followed. Major exclusion criteria included treatment with other investigational drugs within 4 wks of enrollment; life expectancy &lt;2 mos; active coronary artery disease, ischemia, or hypertension; and severe renal impairment requiring dialysis. The primary endpoints were safety and efficacy (per investigator assessed RECIST criteria). Results: Of 2,488 ARCCS pts valid for safety, 65 (2.6%) had been previously treated for BM: 72.3% male with median age 59.5 yrs. 99% had =1 prior therapy for non-brain disease including 81.5 % radiotherapy, 78.5% nephrectomy and 47.7% prior systemic therapy. Grade 3 adverse events (AE) occurring &gt;2% in this subset were fatigue and seizure (6.2% each) and hand-foot skin reaction, diarrhea, hemoglobin, mucositis, dehydration, vomiting, hyperglycemia, and thrombosis (3.1% each). In the total ARCCS population vs the BM subset, Grade 3 AEs were 35.2% vs 26.2% and Grade 4 AEs were 6.1% vs 9%. There were no CNS-related bleeding events in pts with BM. Of the 47 pts evaluable for response, partial response was reported in 2 (4%), stable disease in 33 (70%), and progressive disease in 12 (26%). Conclusions: The toxicity and efficacy of SOR in pts with brain mets in ARCCS were comparable to those observed in the whole study population. Of note, SOR was well tolerated in this study with no reports of cerebral hemorrhagic events. [Table: see text]
Modulation of chemotherapy resistance with low dose suramin in refractory non-small cell lung cancer (NSCLC) patients: A phase I study of sequential non-cross resistant chemotherapy
Authors: T. Olencki, G. Wientjes, G. Otterson, T. Saab, A. Grainger, T. Yeh, R. Jensen, D. Young, J. Au, M. Villalona Calero
Journal: Journal of Clinical Oncology (2005)

2104
Comparison of aprepitant combination regimen with 4-day ondansetron + 4-day dexamethasone for prevention of acute and delayed nausea/vomiting after cisplatin chemotherapy
Authors: M. S. Aapro, H. J. Schmoll, S. Poli-Bigelli, K. Jordan, J. von Pawel, H. Giezek, T. Ahmed, C. Y. Chan
Journal: Journal of Clinical Oncology (2005)

8007 Background: Previous studies showed that aprepitant (APR) + ondansetron (OND) + dexamethasone (DEX) provided better control of acute and delayed chemotherapy-induced nausea and vomiting (CINV) in highly emetogenic chemotherapy (HEC) than OND+DEX. However, OND was given only on the day of chemotherapy (Day 1). These studies did not address whether the APR regimen is superior to OND + DEX when both OND and DEX are given on multiple days to control delayed-phase CINV in patients receiving HEC. Methods: This multinational, randomized, double-blind study compared the APR regimen (APR 125 mg + DEX 12 mg + OND 32 mg i.v. on Day 1, APR 80 mg + DEX 8 mg on Days 2–3, DEX 8 mg on Day 4) with the OND regimen (OND 32 mg i.v. + DEX 20 mg on Day 1, OND 8 mg b.i.d. + DEX 8 mg b.i.d. on Days 2–4) in patients receiving their first cycle of cisplatin (≥70 mg/m2). The primary endpoint was complete response (no vomiting & no use of rescue therapy) in the 120-hr period following cisplatin. Multiplicity adjustments were made for the secondary variables complete response in the delayed phase and no vomiting in the delayed and overall phase. Results: Of 489 adults randomized, 484 were included in the modified intention-to-treat efficacy evaluation. Complete response rates were significantly higher for the APR regimen than for the OND regimen for the overall period (0–120 hr), as well as the acute (0–24 hr) and delayed (>24–120 hr) periods (Table). The APR regimen also provided higher rates of no vomiting over 0–120 hr (76.5% vs 62.2%, p ≤0.001), 0–24 hr (88.9% vs 80.5%, p=0.004), and >24–120 hr (79.0% vs 64.3%, p ≤0.001). Conclusions: The APR regimen was superior to the OND regimen as judged by complete response. This study shows that, in the prevention of delayed CINV, the APR regimen is not only superior to 1-day OND + 4-day DEX, as shown in two previous trials, but is also superior to 4-day OND + 4-day DEX. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Merck Merck Merck Merck
Review of interventions from a sexual health program in an oncology patient population
Authors: A. Amsterdam, M. Castiel, J. Carter, M. Krychman
Journal: Journal of Clinical Oncology (2004)

8170 Background: Sexual problems are common concerns for oncology patients. As treatments for cancer improve and patients live longer, clinicians will encounter more patients with sexual complaints. Re-establishing healthy sexual functioning is an important step towards restoring patients' sense of normalcy. Thus, programs focused on addressing these issues have developed. Methods: A retrospective review was performed using 70 sequential charts of patients who attended the Sexual Health Program at Memorial Sloan-Kettering Cancer Center (MSKCC). Patients were seen from March through September of 2003 and were evaluated by a gynecologist and a psychologist. Results: The median age at the initial visit was 53 (22–76) and the majority of patients were menopausal (90%). The most common cancer diagnoses were breast (31%), endometrial (10%), cervical (10%) and ovarian (9%). Forty patients (57%) had prior pelvic surgery and nineteen (27%) had pelvic irradiation. Non-malignant co-morbidities seen included thyroid disease (21%), depression (20%), hypertension (13%), hyperlipidemia (10%) and diabetes (7%). The most frequent complaint seen was dyspareunia, with (17%) or without vaginal dryness (27%), decreased libido, with (4%) or without vaginal dryness (11%), vaginal dryness alone (8%) or all three complaints in combination (17%). Treatment recommendations consisted of hormonal therapy replacement alternatives such as vaginal moisturizers and lubricants (89%), minimally absorbed vaginal estrogen replacement therapy (49%), vaginal dilators (16%) and psychological counseling (41%). Conclusions: The Sexual Health Program at MSKCC is a multidisciplinary program where female oncology patients with sexual concerns can be evaluated and treated. Patients are diverse in their demographic profiles, cancer therapies and sexual complaints. Current therapeutic options include vaginal lubricants and moisturizers, local hormonal replacement, skilled exercise and psychosexual counseling. Further research is under way to investigate the impact of cancer treatments on the sexual functioning of oncology patients. No significant financial relationships to disclose.
Doxorubicin plus docetaxel as neoadjuvant treatment in patients with large (T&gt;5cm), locally advanced carcinoma of the breast
Authors: S.-H. Lee, J. Y. Lee, Y.-H. Im, J. Park, H. Y. Kim, Y. S. Park, J. H. Kim, S. J. Nam, J. H. Yang, K. Park
Journal: Journal of Clinical Oncology (2004)

746
Efficient detection of <i>EGFR</i> alterations in lung adenocarcinomas.
Authors: M. G. Denis, S. Theoleyre, C. Chaplais, H. Gourdet, S. Caulet-Maugendre, H. Le Ho, R. Corre, H. Lena, C. Sagan, J. Bennouna
Journal: Journal of Clinical Oncology (2010)

10556 Background: Activating mutations of the EGFR gene in lung adenocarcinoma have been associated with response to tyrosine kinase inhibitors. Therefore, a rapid, sensitive assay for mutation detection using routine pathological specimens is demanded in clinical practice to predict patient response. Two types of alterations account for 90% of activating mutations: short in-frame deletions in exon 19 and a specific point mutation in exon 21 at codon 858 (L858R). Methods: We designed a real-time allele-specific PCR to detect the L858R mutation. Exon 19 deletions were detected by length analysis of PCR products using standard polyacrylamide gel electrophoresis. Both assays allowed us to detect an alteration in samples containing 1% of mutated gene, as determined using serial dilutions of DNA of cell lines harboring either exon 19 (NCI-H1650) or 21 (NCI- H1975) mutations. Using these assays, we prospectively studied lung adenocarcinomas collected between April 2007 and July 2009 in Rennes (n = 184), and between september and november 2009 in Nantes (n = 35). DNA was extracted using an automated Bionobis 12GC system (Rennes), or a manual QIAamp DNA minikit (Nantes). Results: We tested samples from 219 patients : 94 females and 125 males (age 33-90; mean 61.6; median 61). Samples tested included fiberoptic bronchial biopsies (n = 90), surgical specimens (n = 75), metastases (n = 32), CT-guided needle biopsies (n = 14), pleural fluids (n = 4) and bronchioalveolar lavages (n = 4). EGFR alterations were identified in 35 (16.0%) patients: exon 19 deletion in 21 cases (9.6%) and L858R mutation in 14 tumors (6.4%). These alterations were more frequent in female (25/94; 26.6%) than in male (10/125; 8.0%; p < 0.001). These results are in complete agreement with the rate of EGFR alteration in Caucasians. The whole procedure can be performed within 24h (from paraffin-embedded sections to results), and the cost of reagents is only ∼20$/test. Conclusions: These assays offer high sensitivity, providing a robust and accessible approach to the rapid identification of most lung cancer patients likely to respond to EGFR inhibitors. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Roche
The temozolomide RESCUE study: A phase II trial of continuous (28/28) dose-intense temozolomide (TMZ) after progression on conventional 5/28 day TMZ in patients with recurrent malignant glioma
Authors: J. R. Perry, W. P. Mason, K. Belanger, P. Kavan, D. Fulton, J. Easaw, S. Kirby, D. Macdonald, C. Shields, J. Pouliot
Journal: Journal of Clinical Oncology (2008)

2010 Background: The combination of radiation with temozolomide (TMZ) 75 mg/m2 x 6 weeks + adjuvant TMZ 150-200 mg/m2 given 5 days out of 28 (5/28) is the standard of care for glioblastoma multiforme (GBM). However, many patients (pts) progress during or after first-line therapy and second-line regimens are only modestly active. Continuous dosing and dose intensification decrease levels of O-6-methylguanine-DNA methyltransferase (MGMT), which has been associated with TMZ resistance. Altering the schedule of TMZ and dose intensification may re-induce chemosensitivity. Methods: After REB-approved informed consent, pts with high-grade glioma who failed the standard TMZ 5/28 adjuvant regimen received continuous dose-intense TMZ 50 mg/m2 for 28 days out of 28 (28/28) for up to one year. The primary endpoint was 6-mo progression-free survival (PFS). The trial used a two-stage design in which at least 1 of the first 15 pts enrolled in each group needed to achieve 6-mo PFS before the next stage was initiated Results: 120 pts were enrolled at 11 centers. Patients were divided into four cohorts: GBM patients failing during the first 3–6 months of adjuvant therapy (B1); GBM patients failing after more than 6 months of therapy (B2); GBM patients who recurred after stopping treatment (B3); and anaplastic glioma pts (A). Median age overall was 52 yrs (25–73 yrs). The majority (66%) were male. ECOG performance status was 0 in 47%, and 1 in 53%. An interim analysis was performed on the first 60 patients. The 6-mo PFS rates were 23% (B1), 7% (B2), 35% (B3), and 53% (A). Nausea and vomiting was observed in less than 5% of patients. Other toxicities were rare. Progressive lymphopenia was observed in some pts but no related clinically significant events have been reported. Prophylaxis for Pneumocystis carinii pneumonia was not required. Conclusions: Continuous dose-intense TMZ 50 mg/m2 given on a 28/28 day schedule is active and well tolerated after failure of the conventional 5/28 day regimen. Efficacy compares favorably to other commonly used second-line agents. Continuous dose-intense TMZ may represent an ideal regimen for use in combination with other agents such as the new targeted therapies. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration Schering-Plough Canada Schering-Plough Schering-Plough Schering-Plough
Facial and dental morphometry screening using photos in children suspected of sleep-disordered breathing
Authors: Nicole Beydon, Laurence Jordan, Guillaume Aubertin, Boris Pételle, Xuan-Lan N'Guyen, Bernard Fleury, Pascal Garrec
Journal: European Respiratory Journal (2014)

Background Skeletal anatomy is studied through cephalometry analysis that is not performed routinely in children with suspected sleep-disordered breathing (SDB). Facial and Dental Morphometry (FDM) partly reflects skeletal conformation and has been related to SDB.

Objectives To assess FDM screening using photos scored by visual inspection and lines construction in children.

Methods Prospective monocentre study conducted in children referred for suspected SDB. FDM was scored by 1) consensus between a pediatrician and an orthodontist on clinical examination 2) full face and profile photos visual inspection by 2 investigators (at least 1 who had not seen the children)3) face and profil lines construction on the photo by an orthodontist who saw the children.

Results We studied 22 children (10 girls, median age 5.3 years; 1.4 to 7.7 years). Inter-observers agreement of visual inspection of the photos was excellent except for the mandibular retrognathia evaluation (table) Dental occlusion was not available on photos in 8 children of whom 6 had less than 3 years of age

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.Intra-observer agreement between clinical examination and lines construction on photos was poorer for dolichofacial and open mandible plane (14 for both out of 22 and 20 studied photos, respectively) than for brachyfacial (19/22 photos).

Conclusion FDM assessment using photos inspection is possible and reproducible. Further studies are warranted to specify the use of objective criteria with respect to that of simple visual inspection.
Effect of Tolbutamide on Blood Pressure
Authors: J K Wales, A M Grant, F W Wolff
Journal: New England Journal of Medicine (1971)

Tolbutamide caused a small increase in blood pressure in the dog. This effect was more marked after reduction of the blood pressure by various hypotensive agents. The increase caused by tolbutamide was still observed after elevation of a reduced blood pressure by norepinephrine, or angiotensin infusion. The effect was not associated with release of insulin brought about by tolbutamide; it was not mediated by catecholamine release, nor by an action of tolbutamide on the kidney. Possible mechanisms are discussed.
Notch Repression by LRF Is Necessary for the Maintenance of Adult Hematopoietic Stem Cell Pool.
Authors: Sung-UK Lee, Min Li, Manami Maeda, Nagisa Sakurai, Yuichi Ishikawa, Freddy Radtke, Minhong Yan, Hugh Robson Macdonald, Takahiro Maeda
Journal: Blood (2010)
Skin reactions with imatinib in CML patients: An Indian experience
Authors: S. V. Attili, G. Anupama, H. K. Dadhich, K. S. Saini, P. P. Bapsy, U. Batra
Journal: Journal of Clinical Oncology (2006)

16522 Background: Skin reactions are observed in up to 30–45% of all patients of CML on imatinib therapy. Owing to its low molecular weight it is less likely to be immunologically mediated. Therefore most of them can be managed without discontinuation of therapy. We tried to look into the spectrum of the skin reactions observed in CML patients receiving imatinib, and tried to see any change with the phase of the disease (chronic/accelerated/blast crisis) or difference in the brand of drug they are receiving. Methods: This retrospective study was conducted at Kidwai Memorial Institute of Oncology, Bangalore, India. A total of 235 patients were analyzed between Jan 2004 and Dec 2005. Clinical details were noted from the case records. Differences were calculated for the means using SPSS 13.0 for windows. Results: The age, total episodes of reactions, mean time to develop and to heal along with grade of reactions are summarized in the table . A total of 191 patients received the international brand and the total episodes of skin reactions observed were 68 with 4 grade III/IV toxicities. 54 patients received local brand and 17 of them developed skin reactions and 2 of which were grade III/IV. There is no difference in the time taken for resolution of skin reactions (23.8 + 6.7 vs. 25.2 + 7.5) (p = NS). Conclusion: There are no significant differences in skin reactions observed with brand of imatinib used. Patients with accelerated phase and blast crisis developed reactions at little earlier. As most of the patients in the later said conditions had a shorter survival, we could not comment conclusively on the time to heal according to phase of the disease. [Table: see text] No significant financial relationships to disclose.