tbuckley/cabot-search huggingface dataset:
Clinical presentation, pathological features, and natural course of metastatic uveal melanoma (MUM) as an orphan and commonly fatal disease
Authors: L. Cerbone, R. Van Ginderdeuren, J. Van den Oord, S. Fieuws, W. Spileers, L. Van Eenoo, A. Wozniak, C. N. Sternberg, P. Schöffski
Journal: Journal of Clinical Oncology (2009)

e20005 Background: Uveal melanoma (UM) is a rare disease characterized by an unpredictable course and variable outcome ranging from cure by local treatment to the occurrence of untreatable metastasis. The current project analyzed patients with the metastatic phenotype. Methods: We performed data collection in 76 pts with MUM treated in Leuven between 1957–2008. Statistical analysis involved nonparametric tests, Kaplan Meyer and log rank test. Results: The med. age at diagnosis of UM was 58 yrs (range 30–94). Common initial treatments were surgery (71%), brachytherapy (20%) and external beam RT (7%). MUM was more common in women (F:M ratio 48:28) and independent from the side of the primary tumor (left vs. right eye). Synchronous metastasis was found in 9% of cases, all others had metachronous disease after a med. interval of 40 mos (range, 7–420). Statistical analysis failed to identify predisposing factors for MUM with the exception of a significant negative correlation between age at diagnosis of UM and time until metastatic disease (Spearman ρ = -0.4, p&lt;0.001). Metastasis in &gt;1 organ, usually liver plus another site, was seen in 47% of cases. The most frequent sites were liver (96%), lung (23%), subcutaneous (13%), bone (11%) and brain (3%).The med. OS from diagnosis of UM was 46 mos (range, 2–182), and 4,5 mos after diagnosis of metastasis (range, 1–128). 65% of MUM pts qualified for further treatment, including systemic therapy (60%), radiotherapy (7%) and surgery (7%). Systemic therapy (45 pts) included mainly chemo- (50%), chemo- plus hormones (12%), immuno- (3%) or hormonal therapy (3%). The most common drugs given were DTIC (43%), cisplatin (27%), tamoxifen (10%) or phase I agents (8%). Patient benefit (PR+SD) was seen in 16/45 pts (36%), including 2 PR. Conclusions: In this orphan disease with female predominance metastasis occurs late, is mainly found but not confined to the liver, and is associated with high morbidity, as &gt;1/3 of pts do not qualify for further therapy. Advances in MUM can only be achieved by networking of sites interested in this tumor with systematic collection of data and tissue to improve our understanding of the molecular biology of the disease. No significant financial relationships to disclose.
Miscellaneous Item
Authors: K T Weber
Journal: Cardiovascular Research (1997)

tarian work in French Equatorial Africa now Gabon .Today, 40 years later, a symposium was held in Libreville to celebrate his 'reverence for life'.Residents in internal medicine from around the world presented clinical vignettes; invited faculty, commentary.Dr. Nick Lewis, from Jamaica, West Indies, began with 'A Case of Rattlebox Disease'.A 16-year-old boy with hepatomegaly since age 8, presented with ascites and cirrhosis.Liver biopsy demonstrated fibrosis and veno-occlusive disease.At 7, his family had treated his flu-like illness with Shack-Shack, a decoction of the leaves of Ž .various plants bush tea , including Crotalaria retusa.Due Ž .to pyrrolizidine alkaloids e.g., monocrotaline , crotalism was first described in horses after C. spectabilis ingestion and termed 'Missouri River bottom disease'.Ripe crotalaria seeds in their pods are called a 'rattlebox'.Professor A, Kimberley, Australia, noted horses ingesting C. retusa developed walkabout disease; they pursued a relentless straight-line course despite obstacles.An association be-Ž .tween these alkaloids and pulmonary hypertension PHT , while not found in man, was seen in rats.Could 'health food' stores sell herbs containing such alkaloids?'Denatured and Re-refined, But Still Repugnant' was presented by Dr. Nick Ortega, Madrid.A 39-year-old woman presented in May, 1981, with fever, cough, dysp-Ž .nea, hypoxemia, eosinophilia eos , and diffuse interstitial X-ray markings.Atypical pneumonia was presumed.In June, she had muscle pain, facial edema, PHT and eos.She Ž .was now recognized as having toxic oil syndrome TOS .TOS afflicted 20 000 Spaniards who ingested adulterated rapeseed oil.In August, scleroderma-like skin lesions, muscle cramps and carpal tunnel were noted with PHT and
Phase I/II study of cetuximab dose-escalation in patients with metastatic colorectal cancer (mCRC) with no or slight skin reactions on cetuximab standard dose treatment (EVEREST): Pharmacokinetic (PK), Pharmacodynamic (PD) and efficacy data
Authors: S. Tejpar, M. Peeters, Y. Humblet, H. Gelderblom, J. Vermorken, F. Viret, B. Glimelius, F. Ciardiello, O. Kisker, E. Van Cutsem
Journal: Journal of Clinical Oncology (2007)

4037 Background: Response to epidermal growth factor receptor (EGFR) inhibitor, cetuximab appears to correlate with the intensity of the associated skin reaction. This randomized study investigated cetuximab dose-escalation in patients (pts) with EGFR-expressing mCRC failing irinotecan-including therapy (I). Methods: Pts were randomized 22 days after starting cetuximab (400 mg/m 2 initial dose then 250 mg/m 2 /week [w]) with I (180 mg/m 2 q 2 w) if they had not experienced &gt;grade (G) 1 skin reaction, any other &gt;G 2 cetuximab-related adverse event and were tolerant to I. Randomization was to standard cetuximab dose (Arm A; 250 mg/m 2 /w) or dose-escalation (Arm B; cetuximab dose increased by 50 mg/m 2 q 2 w, until &gt;G 2 toxicity, tumor response or dose = 500 mg/m 2 ). Pts not randomized (Arm C) continued on standard cetuximab dose. Primary endpoint was to compare in skin and tumor biopsies, taken before and during treatment, the effects of dose-escalation on EGFR and downstream signalling markers with those of the standard cetuximab regimen. Secondary endpoints were PK, efficacy, safety, tolerability, biomarker analyses on tumor biopsies and plasma samples. Results: 284 pts screened, 221 pts EGFR-expressing, 166 pts enrolled and randomized: 45 to Arm A; 44 to Arm B. 77 non-randomized pts were included in Arm C. M/F 106/60, median age 60 years [25–79], median KPS 90 [70–100]. 24 pts in Arm B reached 500 mg/m 2 /w. By the cut-off date of July 31 st 2006 the preliminary response rate (RR) in Arm B was 30% vs. 13% in Arm A. RR in arm C was 22%. Preliminary progression-free survival in Arm A was 3,9 mo vs. 4,8 mo in Arm B and 3,9 mo in Arm C. In Arm B, 9% pts had G 3/4 skin reactions, 0% in Arm A (14% in Arm C). Dose related increases in C max and AUC were observed. T 1/2 values were dose independent. Conclusions: Cetuximab dose- escalation up to 500 mg/m 2 /w improves RR in pts with no or slight skin reactions on standard dose treatment. Overall cetuximab PK behavior is in good agreement with previous experience. Treatment was generally well tolerated. PD and biomarker results will be presented at the meeting. No significant financial relationships to disclose.
A phase II trial of oxaliplatin in patients with advanced melanoma
Authors: J. Lutzky, Y. Nunez, P. Graham
Journal: Journal of Clinical Oncology (2006)

18016 Background: Oxaliplatin is a platinum derivative without nephrotoxicity with in vitro activity against human melanoma cell lines. (Mohammed, MQ, 2000; Tashiro, T, 1989). A Phase I trial suggested activity in melanoma (Mathe, G, 1986) but Phase II data is lacking. A non-nephrotoxic platinum compound active in melanoma is of interest in the development of combination chemo-or chemoimmunotherapy. Methods: This was a Phase II prospective study of oxaliplatin in patients with previously treated or refractory advanced melanoma. The primary endpoint was to evaluate the response rate, survival, freedom from progression (FFP) and the tolerability of oxaliplatin in this patient population. Key inclusion criteria were: metastatic (stage IV) or unresectable malignant melanoma progressing following treatment with at least one and at most three chemotherapy regimens. ECOG PS 0–2, measurable disease and adequate organ and marrow function were required. Oxaliplatin 130 mg/m 2 was given IV in 250–500 mL D5W over 120 minutes every 21 days for at least 2 cycles. Patients were evaluated for response every 2 cycles. Gehan’s two-stage design was utilized. Results: Ten patients were treated between March 2004 and March 2005. Three patients were female and 3 male with a median age of 62.5 years. All patients had PS 0–1. The median number of cycles was 2 (1–6). Three patients had disease stabilization (SD) for median of 3 months. No objective responses were seen; therefore, the study did not progress to the second stage.All patients have progressed and all have expired but one. Median survival from registration was 168 days (128–383). Toxicities included grade 2 fatigue (2 pts) and grade 2 neuropathy (3 pts); one patient had grade 3 diarrhea. Conclusions: Treatment with oxaliplatin in previously treated patients with melanoma is well tolerated at the dose and schedule studied but did not result in objective responses and further development in this population cannot be recommended. Incorporation into combination regimens in previously untreated patients may be of interest. No significant financial relationships to disclose.
Novel in vivo model for drug development in pancreas cancer
Authors: B. Rubio-Viqueira, A. Jimeno, A. Maitra, C. Iacobuzio- Donahue, N. Bouraoud, S. Altiok, C. Yeo, M. Hidalgo
Journal: Journal of Clinical Oncology (2005)

4098 Background: Lack of predictive tumor models is a major limitation in the development of new anticancer therapies. Human xenografted tumors recapitulate more closely the pathobiology of cancer than existing cell lines and could be a better discriminator of the activity of anticancer drugs. Methods: Specimens of pancreatic cancer obtained at the time of surgical resection of patients were implanted in nude mice and expanded to develop a cohort of tumor bearing mice suitable for drug treatment. Mice were treated with inhibitors of the EGFR (erlotinib), MEK (CI-1040) and mTOR (CCI-779) at the dosages of 50 mg/kg/24 h, 150 mg/kg/12h, and 20/mg/kg/24h, respectively. Treatment efficacy was measured by determining the tumor growth inhibition (TGI) on day 28 using a 40% TGI cut off value for activity. Immunohistochemistry (IHC), assessment of activated proteins, profiling and pathway activation by measuring protein-protein interaction, and gene profile were done with tumor samples obtained pre and post-treatment. Results: Thus far we have successfully implanted 20 tumors from 25 patients (success rate 80%) and treated 10 of them. One tumor was susceptible to erlotinib and four tumors each were susceptible to CI-1040 and CCI-779 respectively. Sequencing of genes coding for drug targets and related pathways including EGFR, bRaf, PI3K and mTOR did not show mutations in these genes. Preliminary pharmacodynamic monitoring showed pathway inactivation in responding tumors. Combination treatment in tumors resistant to single agent resulted in antitumor effects in three samples tested. Conclusions: We have successfully generated a model that permits testing of various drugs against a patient individual tumor. This model has several applications: a) because each tumor is from a different patient, this information can be used to guide patient’s treatment at the time of progression; b) as a preclinical screening to prioritize drug/combination of drugs development in pancreatic cancer; and c) to generate a dataset of tumor biology/profile and anticancer susceptibility that permit the establishment of determinants of drug activity. No significant financial relationships to disclose.
Phase 2 results of ABT-751 in subjects with taxane-refractory breast cancer: Interim analysis
Authors: D. K. Washington, A. M. V. Storniolo, M. Saleh, E. Tan-Chiu, A. Hagey, D. M. Medina, K. A. Meek, P. Cernohous, G. B. Gordon
Journal: Journal of Clinical Oncology (2005)

724 Background: Therapy is limited for subjects with taxane-refractory metastatic breast cancer. ABT-751, an oral antimitotic agent that binds to the colchicine site of β-tubulin and prevents microtubule polymerization, has shown antitumor activity in breast xenograft models. In addition, ABT-751 is not an MDR substrate, making it an attractive drug candidate for taxane-refractory patients. Methods: This Phase 2, open label, multi-center study evaluated the safety and efficacy of ABT-751 in subjects with advanced breast cancer (N = 18). For each cycle, subjects received 200 mg ABT-751 orally once daily for 21 consecutive days followed by a 7-day break. Safety was evaluated by adverse events (AEs) and laboratory assessments, while tumor response was assessed radiographically every 2 cycles using RECIST. Time to progression (TTP) was analyzed using Kaplan-Meier methodology. Results: The median duration of therapy was 2 cycles (range 1 to 8). AEs were reported for 17/18 subjects, and 9/18 (50%) subjects experienced serious adverse events (SAEs). The most commonly reported AEs, regardless of causality, were constipation (78%), asthenia (56%), nausea (44%), and abdominal pain (33%). The most common Grade 3 or 4 AEs possibly or probably related to study drug were asthenia (11%), constipation (11%), and ileus (11%). The most common SAE was ileus (17%). Three subjects (17%) experienced SAEs considered possibly related to study drug, the most common of which were ileus (11%) and dehydration (6%). The median TTP was 1.8 months (95% CI = 1.4 - 2.3). There were no partial or complete responses, although two subjects exhibited stable disease for 7 to 8 cycles. All 18 subjects have discontinued the study. This study was designed to target a 25% response rate in an advanced taxane-refractory patient population. The target response rate was not met based on the results of this interim analysis. Conclusions: Although the 21-day dosing regimen for ABT-751 was feasible, these data do not suggest a compelling tumor response with single-agent ABT-751 therapy in this highly advanced, taxane-refractory patient population. Future studies may explore potential synergism between ABT-751 and other cytotoxic agents. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Abbott Laboratories Abbott Laboratories Abbott Laboratories
Imatinib (I) plus etoposide (Vp16) compared to I + cytarabine (Ara-C) for the frontline treatment of accelerated phase (AP) chronic myeloid leukemia (CML)
Authors: E. Cervera, P. Vargas, J. Cruz, V. Enriquez, A. Martinez, V. Lozano, M. Candelaria, J. Labardini, R. Hurtado
Journal: Journal of Clinical Oncology (2007)

7047 Background: Higher doses than 600 mg/day of I is the most recommended initial treatment of advanced CML disease. Nevertheless clinical and molecular results are lower than on early chronic phase, challenging for new treatment developments in face to better results. Main objective of present trial was to increase the hematological (HR) and major cytogenetical responses (MCR) with the addition of Ara- C or Vp16 to I at doses higher than 600 mg/day as a frontline therapy of AP CML. Methods: on march, 2004 we began this multicentric, phase III randomized, clinical trial, comparing I (600 mg/day) plus Vp16 (50 mg PO/day for 7 days/ 21 days cycles) vs I (600 mg/day) plus subcutaneous Ara-C (10 mg/m2/day, for 7 days/21 days cycles), doses could be adjusted due to tolerance and toxicity and in case of failure to respond at 3 months, I doses could be escalated to 800 mg/day. Inclusion criteria: newly diagnosed AP (hematological or clonal evolution permitted) CML, not elective to allogeneic transplant. Primary endpoint was the acquisition and time to acquisition of HR, MCR by conventional criteria. Secondary endpoints were main toxicities, dead to progression and overall survival. Results: 35 patients were randomized with median follow-up pf 487 days (range 21–858) for entire group. Table 1 shows results for both treatment arms. Table 1 Important toxicities (more than grade II) were thrombocytopenia (20%), neutropenia (28%) and gastrointestinal disturbances (32%) for entire group. Statistical analysis for response and toxicity (chi-square, paired T-student, Log-rank survival analysis) did not show significant differences among treatment arms. . Conclusions: We can not observe significant differences among both treatment arms, but important to note is the rates of HR and MCR, suggesting than the addition of chemotherapy could decrease the leukemic burden improving the function of I. Further research is required to confirm this data. No significant financial relationships to disclose. [Table: see text]
Patient weight and event-free survival for children under 2 years of age at diagnosis with favorable histology Wilms tumor
Authors: C. V. Fernandez, J. Anderson, N. Breslow, J. Dome, P. Grundy, E. Perlman, D. Green
Journal: Journal of Clinical Oncology (2007)

20002 Background: Over- and underweight have been associated with excess mortality in certain childhood cancers. The impact of the child’s weight at diagnosis on event-free survival (EFS) in favorable histology Wilms tumor (FH WT) is unknown. Methods: Patients with FH WT under 2 years of age at enrolment on NWTS-5 were included. This age group was analyzed by body weight in kilograms because body mass index (BMI) norms do not exist for individuals less than 2 years old. Outcomes by BMI for children older than 2 years of age with FH WT will be analyzed separately. CDC 2000 growth charts were used. Patients were stratified for risk based on stage and chemotherapy protocol [EE4A = vincristine/dactinomycin] [DD4A = vincristine/doxorubicin/ actinomycin]. A univariate analysis of the relationship of weight-for-age and EFS was calculated. A Cox proportional hazards model was fitted for EFS examining four subsets of weight-for-age by percentiles: a) less than 5%, b) 5–9.9%, c) 90–94.9% and d) more than 95% and adjusting for risk/treatment groups via stratification. Results: 594 patients met the study criteria. 567 had weights recorded. Median follow-up was 4.7 years. 10% of patients had a weight for age percentile of 5.6 or below and 10% had a weight percentile of 94.1 or above. A univariate analysis of the relationship of weight-for-age and EFS showed no relationship (p=0.40, log-rank test). A Cox proportional hazards model, stratified by risk/treatment groups, showed that low or high weight-for-age was not predictive of outcome (p=0.24). Conclusions: There was no evidence that low or high weight-for-age was predictive for EFS among patients less than 2 years old with FH WT. There were more patients with lower or higher weight than would be expected. [Table: see text] No significant financial relationships to disclose.
Early results of a PMH Phase II Consortium trial of AZD0530 in advanced soft tissue sarcoma (STS)
Authors: M. von Mehren, Q. Chu, T. Alcindor, C. Townsley, S. Thallury, K. MacAlpine, J. J. Wright, A. Oza
Journal: Journal of Clinical Oncology (2009)

10579 Background: AZD0530 is a novel oral anilino quinazoline that is selective for c-Src, c-Yes, Lck, and Bcr-Abl through ATP competitive and reversible inhibition of the target enzyme. Src kinases play a role in tumor cell migration, invasion and metastasis as well as being part of the signaling cascade for angiogenesis and growth factors. Advanced STS have limited therapeutic options; therefore we tested the efficacy of AZD0530 in advanced STS. Methods: The study utilized a Simon Two stage design with the primary endpoint be objective tumor response + prolonged stable disease rate (defined as partial/complete response by RECIST, or stable disease &gt;4 months). Patients with measurable advanced STS with up to one prior chemotherapy for metastatic disease were eligible for study participation following informed consent. Patients were excluded for cardiac dysfunction, poorly controlled hypertension, inability to swallow or absorb medication. Patients had pulmonary function tests at baseline that were repeated within the first 4 weeks of therapy. Results: 17 patients (11 F, 6M) with advanced STS (leiomyosarcoma 5, rhabdomyosarcoma 3, MFH/carcinosarcoma/Fibrosarcoma 2, endometrial stromal sarcoma/liposarcoma/non-rhabdoSTS 1 each) were enrolled, the majority of whom had prior therapy (14 chemo and 9 xrt). Five continue on study. Nine discontinued therapy for progressive disease, 2 for toxicity and 1 patient request. Median time to progression in the 13 patients was 1.7 months. Possibly related severe adverse events (all grade 3) included fatigue (2), anemia/lymphopenia/hypokalemia (1 each). To date no confirmed responses have been seen. No drug related pulmonary toxicity has been observed. Conclusions: AZD0530 can be administered safely as a single agent in patients with a variety of advanced STS. To date, tumor responses have not been noted; however patients were not selected based on tumor target expression. Further testing may be warranted in selected tumors in combination with chemotherapy given pre-clinical synergy data or in tumors pre-selected for target expression. No significant financial relationships to disclose.
Trends in Health Care Expenditure in U.S. Adults With Diabetes: 2002–2011
Authors: Mukoso N. Ozieh, Kinfe G. Bishu, Clara E. Dismuke, Leonard E. Egede
Journal: Diabetes Care (2015)

OBJECTIVE Direct medical cost of diabetes in the U.S. has been estimated to be 2.3 times higher relative to individuals without diabetes. This study examines trends in health care expenditures by expenditure category in U.S. adults with diabetes between 2002 and 2011. RESEARCH DESIGN AND METHODS We analyzed 10 years of data representing a weighted population of 189,013,514 U.S. adults aged ≥18 years from the Medical Expenditure Panel Survey. We used a novel two-part model to estimate adjusted mean and incremental medical expenditures by diabetes status, while adjusting for demographics, comorbidities, and time. RESULTS Relative to individuals without diabetes ($5,058 [95% CI 4,949–5,166]), individuals with diabetes ($12,180 [11,775–12,586]) had more than double the unadjusted mean direct expenditures over the 10-year period. After adjustment for confounders, individuals with diabetes had $2,558 (2,266–2,849) significantly higher direct incremental expenditures compared with those without diabetes. For individuals with diabetes, inpatient expenditures rose initially from $4,014 in 2002/2003 to $4,183 in 2004/2005 and then decreased continuously to $3,443 in 2010/2011, while rising steadily for individuals without diabetes. The estimated unadjusted total direct expenditures for individuals with diabetes were $218.6 billion/year and adjusted total incremental expenditures were approximately $46 billion/year. CONCLUSIONS Our findings show that compared with individuals without diabetes, individuals with diabetes had significantly higher health expenditures from 2002 to 2011 and the bulk of the expenditures came from hospital inpatient and prescription expenditures.