tbuckley/cabot-search huggingface dataset:
Metronomic oral cyclophosphamide (CPM) and prednisolone in elderly patients (pts) with inoperable or metastatic soft tissue sarcoma (STS).
Authors: O. Mir, J. Domont, A. Cioffi, S. Bonvalot, B. Boulet, C. le Pechoux, G. Missenard, F. Rimareix, P. Terrier, A. Le Cesne
Journal: Journal of Clinical Oncology (2010)

10065 Background: Conventional doxorubicin-containing chemotherapy regimen may be at risk in elderly STS pts. We assessed the feasibility of treating these pts with metronomic CPM, an attractive regimen characterized by easy oral intake for outpatients, and an original mechanism of action combining immunomodulation and antiangiogenic action. Methods: Elderly (> 65 years) pts with inoperable or metastatic STS unfit for conventional therapy, treated between January 2001 and December 2009 received CPM 100 mg bid and prednisolone 20 mg daily, the first week of a 2-week cycle. Main evaluation criterion was safety. Secondary evaluation criteria were RR, PFS and OS. Results: Twenty-six pts (6 males, median age: 72 years, range 66-88) received a total of 330 cycles (median per pt: 10, range 2-41) as first- (n=19) or second-line (n=7) chemotherapy. Median PS was 2 (range: 1-3), and 77% of pts had a baseline creatinine clearance < 60 ml/min. The most frequent histological subtypes were poorly differenciated STS (8), leiomyosarcoma (5), liposarcoma (5) and angiosarcoma (n = 3). Six sarcomas arose in a pre-irradiated field. Seventeen tumours (65.4%) were grade 3 sarcomas according to the FNCLCC grading system. Clinical and biological toxicity profile was favourable, with only 8% of grade 3 anaemia and thrombocytopenia. A grade 3 lymphopenia was observed in 80% .No other grade 3-4 toxicity was seen. The control rate (CR + PR + SD) was 69.2% (95%CI: 51.5–87.0) including 1 CR (hepatic epithelioid hemangio-endothelioma), 6 PR and 11 SD (≥12 weeks). Interestingly 5 PR were observed in radiation- induced sarcomas. The median PFS was 6.8 months (range 0 to 20.6 months. PFS was significantly longer in patients with radiation-induced sarcomas (median: 7.8 vs. 5.2 months, p = 0.02). Median OS was 14.1 months (1.2-30.4). Conclusions: Despite a high-risk profile for toxicities, elderly pts could tolerate and benefit from this regimen, with unusual responses in pts with radiation- induced sarcoma. A larger, prospective study is warranted to confirm these findings in elderly STS pts. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Novartis, Pfizer, PharmaMar Novartis, Pfizer, PharmaMar
The effects of interferon beta on cold-induced asthma exacerbations
Authors: Ratko Djukanovic, Tim Harrison, Phillip Monk, Neil Thomson, Sebastian Johnston, Stephen Holgate, Donna Davies
Journal: European Respiratory Journal (2012)

In vitro studies show that asthmatic bronchial epithelial cells produce insufficient interferon beta (IFNb) when infected with rhinovirus (RV), whilst exogenous IFNb restores their capability to stop viral replication. This has provided pre-clinical POC for innate immune deficiency in asthma and a rationale for a randomised placebo controlled clinical trial of aerosolised IFNb. The trial involved 21 centres and 147 asthmatics, with the sACQ (shortened Asthma Control Questionnaire) as the primary outcome. Patients commenced treatment at the onset of common cold symptoms and, following baseline assessment, were treated daily for 2 wks with IFNb (6MIU) or placebo.134 patients fulfilled the Jackson criteria for a cold (mITT population): in these, respiratory viruses were detected in nasal lavage by PCR in 63% of patients (68% RV+). In the placebo group, cold symptoms correlated strongly with those of asthma and only patients with difficult to treat asthma (BTS steps 4 and 5) had a clinically relevant (>0.5) increase in sACQ, whilst step 2 or 3 asthmatics did not. In the difficult to treat patients the difference in sACQ during the first week was 0.63 (p=0.004) in favour of treatment and the % experiencing an exacerbation was significantly (p=0.012) lower. Treatment with IFNb also resulted in significantly faster recovery of PEF and less use of b2-agonists (p<0.05). This trial suggests that treatment with inhaled IFNb significantly attenuates the adverse effects of the common cold in difficult to treat asthma patients whose needs for such treatment are greatest. The study provides rationale for follow on clinical trials. (The trial was funded by Synairgen plc and supported by NIHR).
Impact of medicaid-enrollment status/timing on stage at diagnosis among male cancer patients.
Authors: K. S. Virgo, A. Pavluck, A. Y. Chen, N. M. Marlow, H. Kirby, C. Finney, E. M. Ward
Journal: Journal of Clinical Oncology (2010)

6038 Background: Past research indicates that uninsured and Medicaid-insured cancer patients have an increased risk of late stage at diagnosis compared to Medicare- or privately-insured patients. State projects (Michigan, California, Washington) have reported late stage at diagnosis among patients enrolled in Medicaid after diagnosis for 4 cancer sites. We assessed the relationship between Medicaid-enrollment status/timing and stage at diagnosis for 10 cancer sites, focusing on males in South Carolina. We hypothesized that late enrollment would be associated with late stage at diagnosis for most sites. Methods: Secondary data were extracted from the South Carolina Cancer Registry and Medicaid program. Male patients ages 18-64 diagnosed during 1996-2005 with a first invasive primary cancer of the lung/bronchus, prostate, colon, rectum, kidney/renal pelvis, thyroid, pancreas, or urinary bladder and patients with melanoma (skin) or NHL with nonmissing vital status or staging data were selected for analysis. The relationship between enrollment status (non-Medicaid as referent) and stage at diagnosis was examined using multivariate logistic regression analysis. Patients continuously enrolled in Medicaid for at least the month prior to and the month of diagnosis were considered enrolled prior to diagnosis. Those enrolled in the diagnosis month or thereafter and not enrolled in the month prior to diagnosis were considered late enrolled. Results: Of 22,280 evaluable patients, late Medicaid enrollees were more likely (p < 0.0001) to be late stage (84%) than patients enrolled prior to diagnosis (58%) or non-Medicaid-enrolled patients (40%). Compared to non-Medicaid patients, the odds of advanced stage were 3.44 (CI = 2.90-4.07) for late Medicaid enrollees and 1.22 (CI = 1.07-1.39) for patients enrolled prior to diagnosis after controlling for all other factors. Conclusions: Variation in stage at diagnosis between Medicaid-insured and non-Medicaid-insured males was generally greatest for cancer sites for which screening is recommended. For almost all cancer sites, males who were Medicaid enrolled after their cancer diagnosis were significantly more likely to be diagnosed with late-stage disease. No significant financial relationships to disclose.
Severe Early-Onset Inflammatory Bowel Disease Caused by IL10 Receptor Deficiency Can Be Cured by Allogeneic Hematopoietic Stem Cell Transplantation.
Authors: Kaan Boztug, Daniel Kotlarz, Erik Glocker, Mike E Gertz, Alejandro A Schäffer, Fatih Noyan, Mario Perro, Jana Diestelhorst, Anna Allroth, Dhaarini Murugan, Nadine Hätscher, Dietmar Pfeifer, Karl-Walter Sykora, Martin Sauer, Hans Kreipe, Martin Lacher, Rainer Nustede, Cristina Woellner, Ulrich Baumann, Ulrich Salzer, Sibylle Koletzko, Neil Shah, Anthony Segal, Axel Sauerbrey, Stefan Buderus, Scott Snapper, Bodo Grimbacher, Christoph Klein
Journal: Blood (2009)
Primary sarcomas of the lungs and mediastinum: Clinicopathological study and therapy results of Piedmontese Group for Sarcomas
Authors: A. Comandone, A. Boglione, P. Pochettino, E. Berno, M. Inguì, M. Papotti, P. Borasio, G. Maggi, E. Brach del Prever, G. Gino
Journal: Journal of Clinical Oncology (2009)

e21509 Background: Primary sarcomas of the lungs and mediastinum are rare and few data are reported on treatment and results of therapy. Methods: We reviewed our experience from 1980 and 2008 including 31 patients (pts). Pts characteristics: median age 41 (19–80 y), male/female 19/12; symptoms at diagnosis: dyspnoea (42%), chest and shoulder pain (39%), cough (35%), hemophtoae (13%), discomfort (10%). 4 pts had a previous history of mediastinal radiation for Hodgkin's and non-Hodgkin's linfomas. 5 mediastinal tumours were located as follows: 2 in anterior part, 1 in posterior and 2 in the middle (sarcomas of the heart). 26 lung sarcomas presented as a singular mass in 23 cases and as a metastatic disease in 3. Results: In 20/31 cases the tumour was immediately resected (3 mediastinal masses and 17 lung sarcomas). In 8/31 cases only biopsy was possible. FNA was done in 25 pts. Neoadjuvant chemotherapy was performed in 4 cases (3 resected). Resection was complete in 11/23 cases and in 12/23 incomplete. The histology were: peripheral nerve tumour 7, leiomyosarcoma 4, MFH 2, fibrosarcoma 2, liposarcoma 1, angiosarcoma 2, undifferentiated sarcoma 1, solitary fibrous tumour 2, rhabdomyosarcoma 2, synovialsarcoma 2, pulmonary artery sarcoma 1, pleuropolmonary blastoma 1, malignant hemangiopericytoma 1, mixoid chondrosarcoma 1, ectopic osteosarcoma 1, aggressive fibromatosis 1. Only 4 pts received neoadjuvant chemotherapy, 11 adjuvant CT, 5 exclusive CT + RT for inoperable disease. Radiotherapy was completed in 26 pts (21 adjuvant). Local relapse or metastatic progression were recorded in 16/23 pts and 12 received one or more lines of palliative CT. Data about survival are disposable only for the more recently recorded pts (1998–2008: 17 pts). Of these only 8 are alive (2 with disease). Volume of disease, complete resection and grading are the dominant prognostic factors. Conclusions: Primary sarcomas of the lungs and mediastinum have a very severe prognosis. Surgical resection is the fundamental therapy, but in the future the role of neoadjuvant CT will increase. No significant financial relationships to disclose.
Design and first interim analysis of a randomized phase III trial comparing imatinib versus imatinib (IM) based combination therapies in newly diagnosed chronic myelogenous leukemia patients in chronic phase
Authors: F. Maloisel, V. Dubruille, B. Varet, M. Escoffre-Barbe, P. Berthaud, V. Meresse, F. Mahon, C. Preudhomme, J. Guilhot, F. Guilhot
Journal: Journal of Clinical Oncology (2006)

6589 Background: Despite impressive results achieved with IM 400 mg/day alone, only a minority of pts reached a complete molecular remission at 12-month. Higher dose of IM or its combination with other therapies might improve molecular remission. Design of the trial: the 3 experimental arms are IM 400mg daily in combination with Peg-IFN-α2a (Peg-IFNα2a, 90 μg weekly) or with Ara-C (20 mg/m 2 /day, days 15–28 of 28-day cycles) or IM 600mg daily. The reference arm is IM 400mg daily. All pts (over 18 years of age with Bcr-Abl positive CML) receive IM 400 mg/day as monotherapy days 1–14 and then start the assigned regimen for at least 12 months. The endpoints are overall survival (primary), rate and duration of hematologic, cytogenetic and molecular responses and tolerability. An interim analysis of the first 636 pts at 1 year from randomization will allow evaluation of molecular response rates, one of the experimental arm being selected for further comparison with IM 400. An experimental arm would be selected if it increased the 4 log reduction response rate at 12-month by at least 20 percentage points, (15% to 35%), with an acceptable tolerability. Results: This evaluation is based on a cohort of 370 pts with a median time of observation of 16 months, recruited between 9/2003 and 9/2005. [median age 53 yrs (18–81); Sokal distribution: 38% of pts low, 38% intermediate, and 24% high]. At 1 month 80% of pts achieved complete hematologic response. At 12 months, 138 pts (72%) achieved a major cytogenetic response, being complete in 120 pts (63%). Grade 3/4 hematologic toxicity occurred in 8% of IM400 pts, 9% of IM600 pts, 41% of IM+IFN pts and 33% of IM+Ara-c pts respectively. Dose of Peg IFN was reduced in 16% of pts, 45 μg per week being well tolerated. Grade 3/4 non hematological toxicity occurred in 11% of IM400 pts, 16% of IM600 pts, 10% of IM+IFN pts (maily skin rash) and 11% of IM+Ara-c pts. Discontinuation of experimental treatment occurred in 17% of IM600 pts, 36% of IM+IFN pts and 16% of IM+Ara-c pts. Conclusion: This first analysis confirmed both feasibility of IM combinations and high response rates. However a substantial hematological toxicity requires a careful assessment of pts. [Table: see text]
A phase II study of lonafarnib (SCH66336) in patients with chemo-refractory advanced head and neck squamous cell carcinoma (HNSCC)
Authors: C. H. Yang, M. S. Kies, B. Glisson, B. J. Burke, L. E. Ginsberg, M. T. Truong, M. M. Sugrue, W. K. Hong, F. R. Khuri, E. S. Kim
Journal: Journal of Clinical Oncology (2005)

5565 Background: Treatment options for advanced disease are limited and for those patients failing chemotherapy, there are few viable options. Lonafarnib is a novel tricyclic peptidomimetic compound that is a potent and specific inhibitor of farnesyl protein transferase. We have previously reported clinical activity of lonafarnib in untreated HNSCC (4 of 22 patients showed response despite drug exposure for only 7–14 days). We proposed to assess the activity of lonafarnib in advanced HNSCC patients. Methods: An open-label phase II single-center study was conducted to determine the objective response rate of lonafarnib administered at 200 mg bid, enrolling patients who were incurable and who failed at least one platinum-containing regimen, but received no more than three prior regimens. Results: Fifteen patients, aged 32 to 66 (median age 57) were enrolled. All patients had baseline ECOG PS 0 or 1. Median treatment duration was 61 days (range 0–224 days). Median time to progression was 62 days. No objective response was observed. Seven (47%) of the 15 patients maintained stable disease through at least 3 cycles of therapy, and 1 patient maintained stable disease for 8 cycles of therapy (220 days). No treatment related deaths were reported. Grade 4 hyperuricemia occurred in one (7%) patient. Grade 3 adverse effects included anorexia, infection without neutropenia, QTc elongation and syncope reported in one (7%) patient each, respectively. No significant grade 3 or 4 hematologic toxicities were reported, with grade 2 anemia noted in 2 patients. The most common toxicities were grade 1 or 2 and included diarrhea in 10 (67%), nausea in 9 (60%) and fatigue in 7 (47%) of the patients, respectively. Conclusions: Lonafarnib was well tolerated and demonstrated disease control in patients. Although there were no objective responses observed in this small open-label study, the low toxicity and disease control warrant further studies in chemo-refractory head and neck cancer patients. Biomarker analysis of the tissue is ongoing at this time including markers of k-ras, p-akt and others. No significant financial relationships to disclose.
Role of Laparoscopic Surgery in the Management of Endometrial Cancer
Authors: Meaghan Tenney, Joan L. Walker
Journal: Journal of the National Comprehensive Cancer Network (2009)

Minimum surgical treatment for endometrial cancer is removal of the uterus. The operative approach to achieve that goal ranges from vaginal hysterectomy alone to laparotomy with radical hysterectomy, bilateral salpingoophorectomy, bilateral pelvic and para-aortic lymphadenectomy with possible omentectomy, and resection of all metastatic disease. Stratifying the risk factors for predicting presence of metastatic disease has error rates exceeding tolerance for many gynecologic oncologists. Most accept routine laparoscopic surgical staging with hysterectomy, pelvic and para-aortic lymphadenectomy, and removal of adnexa as standard care for patients with endometrial cancer. Modifying the extent of surgical staging for low-risk intrauterine findings or excessive risk for postoperative morbidity is also accepted. Laparoscopic surgery has become the ideal initial surgical approach for this disease, allowing for visual inspection of common metastatic sites, biopsy of abnormal areas, and cytology from peritoneal surfaces. The extent of staging can be altered depending on frozen section findings from the uterus, adnexa, and peritoneal surfaces. Intraoperative medical decision-making can be individualized, encompassing all known risk factors for metastases and balancing comorbidities and potential adverse outcomes. This article documents how laparoscopic surgery satisfies the needs of individual patients and surgeons treating this disease.
Disposition of drugs in man by radioimmunoassay.
Authors: S Spector
Journal: Pharmacological Reviews (1982)

The disposition of morphine and clonidine was investigated by means of radioimmunoassay. After the administration of a single i.v. dose of morphine (10 mg/70 kg) to 10 men who had not received other drugs for two weeks preceding the study, a multiphasic decline in serum concentrations of morphine occurred. Detectable blood concentrations of morphine, or a metabolite, or of both, persisted for up to 96 hours after a single i.v. dose. The radioimmunoassay for clonidine is capable of detecting as little as 10 pg of clonidine. The antibody fails to bind 2,6-dichlorophenylguanidine, a known metabolite of clonidine, while the other metabolite, 4-hydroxyclonidine, was as potent as clonidine in displacing labeled clonidine from the antibody. The disposition of clonidine ion plasma and tissues could be monitored by radioimmunoassay.
Amenorrhea in premenopausal women on the doxorubicin (A) and cyclophosphamide (C) → docetaxel (T) arm of NSABP B-30: Preliminary results
Authors: S. M. Swain, S. R. Land, R. Sundry, M. Ritter, J. Costantino, N. Wolmark, P. A. Ganz
Journal: Journal of Clinical Oncology (2005)

537 Background: NSABP B-30, an adjuvant study with 3 chemotherapy treatment arms in node-positive breast cancer, accrued 5351 patients (pts) from 1999–2004. A secondary objective of this study was to document menstrual history (MH) in premenopausal women in each treatment arm and its relationship to symptoms, quality of life (QOL), disease-free survival, and survival. This report describes preliminary results re MH in the AC ⋄ T arm. Methods: Pts completed a baseline and MH follow-up form day 1 cycle 4 (D1C4), and 6, 12, 18, 24 months (mo) after randomization. Pts < 60 yrs who had been on study ≥ 24 mo were included in this analysis. Results: Of the 528 pts with 24-mo follow-up in the MH study, 490 pts (93%) were menstruating regularly at start of chemotherapy, with 17% of these pts amenorrheic for ≥ 3 mo by D1C4. Including full length of follow-up, 80% reported amenorrhea ≥ 6 mo, 11% for ≥ 3 mo, 4% changes in menstrual cycles, and 5% no changes. The table provides rates of amenorrhea at 6- and 12-month follow-up by age and tamoxifen usage. In a sensitivity analysis designed to account for missing data, median duration of amenorrhea for pts ≤ 30 yrs was estimated to be 3–13 mo; 30.1–40 yrs 9–17 mo; 40.1–60 yrs >24 mo. 354 pts participated in both QOL and MH studies. Menstrual status was not a significant predictor of the FACT-B Trial Outcome Index in repeated measures analysis (p=0.35). Conclusions: Amenorrhea occurred in a substantial percent of women after AC⋄ T, which increased with age. There was no correlation with QOL in this early analysis. Future studies include time to amenorrhea and examine the association of amenorrhea with body mass index and race. No significant financial relationships to disclose.
Brain and Spinal Cord Tumors in Rats Treated With Pyrrolizidine Alkaloids
Authors: R. Schoental, J. B. Cavanagh
Journal: JNCI Journal of the National Cancer Institute (1972)

Two spinal cord tumors and one brain tumor occurred among rats treated with various pyrrolizidine alkaloids. One spinal cord tumor was found in a paraplegic female rat 213 days old, the mother of which was given a Bedu remedy, Heliotropium ramosissimum in the diet, during part of pregnancy and lactation and to the young when 6 months old; the other spinal cord tumor was in a paraplegic male rat killed 201 days after a single subcutaneous dose of retronecine given when the rat was newborn. A male rat killed 445 days after it received, as a weanling, a single intraperitoneal dose of hydroxysenkirkine from Crotalaria laburnifolia variety laburnifolia had an astrocytoma of the cerebrum. “Natural” carcinogens such as the pyrrolizidine alkaloids may play a part in the etiology of tumors of the central nervous system in animals and man exposed at the perinatal age to the hazards of such materials.
Silencing transcription-coupled nucleotide excision repair (TC-NER) pathway results in increased sensitivity of bladder cancer cells with Cisplatin treatment
Authors: Xiaoxin Xu, Dongshu Liu, Stephanie Colton, Gan Wang
Journal: Cancer Research (2007)

1968  Many anticancer drugs target the genomic DNA of cancer cells by generating DNA damage and blocking DNA replication and gene transcription, resulting in a programmed cell death (apoptosis). However, DNA repair effectively removes DNA damage and results in increased tumor cell resistance to these drugs. Nucleotide excision repair (NER) is the major DNA repair pathway that repairs bulky DNA damage generated by environmental agents and therapeutic drugs. We have studied the possibility of sensitizing tumor cells to anticancer drug Cisplatin via disturbing transcription-coupled NER (TC-NER or TCR) pathway by small interference RNAs (siRNA). The TC-NER is a sub-pathway of the NER process that quickly removes DNA damage generated in highly transcribed genes with high efficiency. The siRNAs that effectively silence the CSB, XPA, and XPG genes of the TC-NER pathway were identified. The results obtained from our caspase-3 activation assay revealed that silencing these genes caused elevated caspase-3 activation of both HT1197 and T24 bladder cancer cells following Cisplatin treatment. The western blot results indicated that disturbing the TC-NER pathway resulted in more enhanced CHK1 and p53 phosphorylation and increased expression of pro-apoptotic PUMA protein with Cisplatin treatment. The results obtained from host cell reactivation (HCR) assay indicated that silencing these genes led to reduced DNA repair capacities of these cells. These results suggest that disrupting the TC-NER pathway with siRNAs enhances the sensitivity of bladder cancer cells with Cisplatin treatment. Therefore, disturbing the TC-NER function may provide a novel strategy to sensitize cancer cells to DNA damaging anticancer drugs.