tbuckley/cabot-search huggingface dataset:
Arsenic trioxide in patients with myelodysplastic syndromes (MDS): Preliminary results of a phase II clinical study
Authors: A. F. List, G. J. Schiller, J. Mason, D. Douer, R. Ellison
Journal: Journal of Clinical Oncology (2004)

6512 Background: Trisenox (arsenic trioxide –ATO) is a novel anticancer agent approved for the treatment of relapsed or refractory acute promyelocytic leukemia. ATO has unique mechanisms of action that impact apoptotic threshold and differentiation in leukemia cell lines and hematopoietic malignancies. To investigate the activity of ATO in MDS, we performed a study in pts from Low/Int-1 (LR) and Int-2/High risk (HR) IPSS categories. Methods: Pts received ATO at 0.25 mg/kg via a 1–2 hour IV infusion, Monday to Friday, 2 consecutive wks every 28 days. Disease response and toxicity were assessed using the International Working Group (IWG) criteria and NCI CTC v2, respectively. Results: 53 pts are enrolled: 4 received no study drug and 3 are too early in treatment to assess. Among the 46 evaluable pts (29 M/17 F; median age 69, [35–93]), FAB categories were RA (6 pts), RARS (9), RAEB (18), RAEB-t (11), and CMML (2). Twenty-five pts were HR and 21 were LR MDS. The median interval from diagnosis to first dose was 7 months (0–81). Thirty-five pts were transfusion-dependent (TD). Hematologic responses were observed in 12 of 46 evaluable pts (26%); 8/21 LR pts (38%), and 4/25 HR pts (16%). Responses included 9 erythroid (5 major, including 1 CR), 3 major platelet, and 2 major neutrophil. Confirmed responses were seen after 2 to 6.1 months of treatment and lasted from 2 to >8 months on study, with 1 pt maintaining response for >21 months off study. Four TD pts became transfusion-independent, and transfusion requirements in 3 others decreased by ≥50%. Stable disease lasting >8 weeks was observed in 8 additional HR pts. Grades (gr) 3–4 adverse events considered drug-related that were observed in ≥2 pts included fatigue, febrile neutropenia, dyspnea, urinary tract infection, hyperglycemia, congestive heart failure, hypoxia, herpes infection, and pleural effusion. Some cytopenias were exacerbated, resulting in 1 gr 3 and 2 gr 4 neutropenias, and 3 gr 3 and 1 gr 4 thrombocytopenias. Conclusions: ATO demonstrates multilineage hematopoietic activity in both LR and HR MDS pts. ATO is well tolerated, as most treatment-related adverse events were mild to moderate. Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Cell Therapeutics, Inc. Cell Therapeutics, Inc. Cell Therapeutics, Inc.
Correlation of SPARC, ER, PR, and HER2 tumor with progression-free survival from a phase II neoadjuvant trial of gemcitabine, epirubicin, and nab-paclitaxel
Authors: R. C. Inhorn, B. Daniel, D. Daniel, Y. Naot, J. Zubkus, C. Lane, V. Trieu, D. Knauer, N. Desai, D. A. Yardley
Journal: Journal of Clinical Oncology (2009)

618 Background: Neoadjuvant combinations of gemcitabine (G), anthracyclines and taxanes have demonstrated substantial activity with pCR rates of 20–25%. Secreted protein acidic rich in cysteine (SPARC) is an albumin binding protein that mediates intratumoral accumulation of nab-paclitaxel (nab-P) via a SPARC-albumin binding activity and is a poor prognostic factor for survival. This study was designed to evaluate the feasibility and safety of a biweekly schedule of neoadjuvant nab paclitaxel (nab-P) with G and epirubicin (E) with SPARC tumor assessments performed in consenting patients (pts). Methods: Eligibility: Clinical T1c-T4d and/or N0–3, M0 breast cancer (T1N0M0 excluded), normal LVEF. ER/PR/HER-2 obtained for all pts. Treatment: neoadjuvant G 2,000 mg/m 2 , E 50 mg/m 2 , and nab-P 175 mg/m 2 q14 days x 6 cycles followed by surgery. Post operative therapy: G 2,000 mg/m 2 and nab-P 220 mg/m 2 q14 days x 4 cycles. Myeloid growth factors were mandated with all cycles. Two different antibody reagents were used to probe for SPARC expression of tumoral SPARC and stromal SPARC; level 3 immunohistochemical (IHC) SPARC staining was considered positive. Results: 123 pts enrolled. Pathologic responses are available for 112 pts with 11 unevaluable. 82 pts consented to SPARC tumor testing. Median age 51 (29–72). Median tumor size 4.5 cm. 42% ER- / PR -. 55% clinical T3/T4 and 66% node positive. Pathologic complete responses (pCR) were noted in 22 pts (18%) with PRs in 84 pts (68%), and 6 SD (5%). SPARC IHC staining was available in 77 tumor samples; SPARC positivity was noted in 89% of evaluated tumors achieving pCR. Triple negative, ER negative or PR negative tumors were associated with worse PFS. SPARC + tumors showed a trend to improved PFS that was strongly associated with tumoral SPARC but not stromal SPARC. Conclusions: Dose dense neoadjuvant G, E, and nab-P is active and well tolerated with a favorable pCR rate of 20%. ER neg, PR neg, and triple negative tumors were associated with worse PFS. Despite literature reports of SPARC positivity associated with poor prognosis, SPARC+ tumors in this study showed a high concordance with tumor response and a trend to improved PFS with tumoral SPARC. [Table: see text]
Combined effect of para-aminobenzoic acid (PABA) and ionizing radiation in a syngeneic murine model of breast carcinoma
Authors: A. Bertkau, S. MacDonald, J. Roth, M. Caunt, P. Brooks, S. Formenti
Journal: Journal of Clinical Oncology (2004)

3189 Background: PABA or p-amino benzoic acid is a water-soluble natural compound and a component of Vitamin B-12, thought to play a role in nucleotide base synthesis. It is widely available as a dietary supplement and is a common component of sunscreens. Previously, we observed that PABA enhanced the effects of radiation in B16F10 and G361 melanoma and Lewis Lung carcinoma in vitro, as well as in 4T1 breast carcinoma and B16F10 melanoma in a chick CAM in vivo model (ACR-NCI-EORTC, Nov. 2003). To further explore the role of PABA pre-clinically, we studied its effects as a radiosensitizer in the 4T1 syngeneic murine model of mammary carcinoma (Fred Miller, The Michigan Cancer Center). Methods: 4T1 tumor cells (5 x 104) were injected subcutaneously into the flank of BALB/C mice. Three days later, 28 mice were randomly assigned to PABA, administered daily for the duration of the experiment (1 mg/day), or no PABA treatment. At 14 days post-implantation, a randomization to radiation treatment (RT) occurred in both the PABA and non-PABA treated groups. A 60Co source was used to deliver a single fraction of 10 Gy to the tumor. Tumors were measured and volumes were calculated weekly for 28 days ((L2xW)/2). Results: At day 28, PABA injection alone had minimal effect on tumor growth (P=0.14); 10 Gy of ionizing radiation therapy significantly inhibited tumor growth by 47% (P=0.019); and PABA+10 Gy RT significantly inhibited tumor growth by 83% (P=0.000217) as compared to untreated controls. In addition, PABA+10 Gy RT resulted in a 68% inhibition of tumor growth as compared to radiation alone (P=0.00036). Conclusions: The most effective inhibition of tumor growth was achieved by PABA+10 Gy RT, suggesting that PABA is a radiosensitizer in this model. Given the high tolerability of PABA, these data may have significant translational potential. No significant financial relationships to disclose.
Effect of gabapentin on anxiety among 306 breast cancer patients: A URCC CCOP study.
Authors: O. Palesh, J. E. Lavigne, K. M. Mustian, L. J. Peppone, C. E. Heckler, M. C. Janelsins, J. Mathews, J. Q. Purnell, L. Sprod, G. R. Morrow
Journal: Journal of Clinical Oncology (2010)

9148 Background: Anxiety is prevalent among 18%-77% of cancer patients and is associated with increased insomnia, depression, fatigue and reduced quality of life. In a previous study, we found that gabapentin is effective in reducing hot flashes among cancer patients. Gabapentin is used for treatment of anxiety disorders but there is little scientific evidence supporting its use. The aim of this secondary data analysis is to examine the effect of gabapentin on anxiety. Methods: 420 breast cancer patients experiencing ≥ 2 hot flashes a day were randomized to placebo, gabapentin 300 mg/day, or gabapentin 900 mg/day for 8 weeks (wks). Anxiety was measured by the State-Trait Anxiety Inventory (STAI) at baseline, 4 and 8 wks. Results: At 4 wks, patients (n = 334) receiving gabapentin 300mg reported a reduction in anxiety (change score [CS] = -2.08, standard error [SE] = 0.89) while patients receiving gabapentin 900mg and placebo reported an increase in anxiety (900 mg CS = +0.32, SE = 0.87, placebo CS = +1.01, SE = 0.76). At 8 wks, patients (n = 306) receiving gabapentin 300mg reported a further reduction in anxiety (CS = -2.65, SE = 0.86) while patients receiving gabapentin 900mg and placebo continued to reported increases in anxiety (900 mg CS = +0.16, SE = 1.03, placebo CS = +1.89, SE = 0.97). ANCOVAs controlling for baseline anxiety revealed significantly lower anxiety at 4 and 8 wks among patients receiving gabapentin 300 mg compared to patients receiving placebo (all p < 0.05) with no significant differences between patients receiving gabapentin 900 mg and those receiving placebo. ANCOVAs also showed a significant baseline by treatment interaction at 4 wks (p < 0.05); where patients with higher baseline anxiety reported the greatest reductions in anxiety, but this interaction effect was not present at 8 wks. Conclusions: Gabapentin administered at 300 mg/day is useful in reducing anxiety experienced by breast cancer patients and may be particularly useful for patients experiencing high levels of anxiety short-term. The 300 mg dose may be more effective compared to the 900 mg dose due to an anxiety receptor-specific physiological effect and/or the combination of fewer drug-related toxicities resulting from the lower dose. Funding: U10CA37420 and K07CA132916. No significant financial relationships to disclose.
A phase II study of depsipeptide (Dep) in patients (pts) with metastatic renal cell cancer (RCC)
Authors: W. M. Stadler, J. N. Swerdloff, K. Margolin, B. McCulloch, J. Thompson
Journal: Journal of Clinical Oncology (2005)

4669 Background: Metastatic RCC is poorly responsive to current available systemic therapies. Multiple genes thought to be important in RCC development and progression are inactivated by methylation and histone deacetylation. Dep is a natural product with potent histone deacetylase inhibitory and anti-tumor properties in preclinical and phase I studies. Methods: Pts with metastatic RCC and normal organ function who failed prior cytokine therapy were treated with 13 mg/m2 Dep weekly (wk) for 3 wks out of 4. The statistical plan specified an initial enrollment of 16 pts with further enrollment to 25 if at least 1 RECIST response was observed. Results: 30 pts were enrolled from 3 institutions of which 29 received at least 1 dose and are evaluable. Baseline characteristics included M/F (21/8), median (range) age 59 (41–79), time from diagnoses 2.4 yrs (0.6–15.2), and number of prior therapies 2 (2–12). Major grade 3/4 toxicities included fatigue (5), nausea/vomiting (4), anemia (3), anorexia (2), dehydration (2), cardiac rhythm disturbances without sequelae (2), and asymptomatic prolonged QTc (1). Grade 1/2 constitutional symptoms were common with nausea (27), fatigue (21), dysgeusia (8), dizziness (6), rigors (5), and myalgias (5) reported. Ten pts required dose delay/adjustment and 12 pts discontinued therapy early (including 3 prior to response evaluation) at least in part due to toxicities. There was one CR and one unconfirmed PR (7% overall response rate), but on review, the pt with CR had a baseline lesion of only 9mm. Neither responder had any unique pathologic characteristics. Median time to progression was 12 weeks. Conclusions: The response and toxicity profile indicate that further investigation of Dep in RCC should focus on identifying predictors of response, possible growth inhibitory (rather than cytotoxic) properties, or activity in rationally derived combinations. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Gloucester Gloucester
Trends in patient copays for hospital and office-based chemotherapy 2005-2012 for Medicare and commercially insured patients.
Authors: Kathleen A. Foley, Rebecca Bechhold
Journal: Journal of Clinical Oncology (2013)

260 Background: With the growing shift towards chemotherapy administration in outpatient hospital settings (OHS) versus office-based settings (OBS), we sought to characterize the percent of patients with a copay and the mean copayment by setting and insurance type over time. Methods: Using the MarketScan Research Databases, first administrations of bevacizumab and trastuzumab were identified from 1/1/2005 through 12/31/2012 for patients with commercial or employer-sponsored supplemental Medicare insurance. Bevacizumab claims were excluded if the claim had a diagnosis related to macular degeneration or other eye disease. All claims were identified in OHS, OBS, or other setting. Results: The percent of patients with a copayment varied by insurer and setting but within each group remained fairly consistent over time. The average percent with a copay was 14% OHS and 19% OBS for commercial and 17% OHS and 28% OBS for Medicare patients. Per administration copayment amounts varied over time, with peaks of $978 OHS and $631 OBS for commercial in 2012 and $721 OHS and $464 OBS in 2011 for Medicare with 2012 Medicare copayments declining somewhat for bevacizumab. For herceptin peak mean copayments were $886 and $439 in 2012 for OHS and OBS commercial patients, respectively, and $458 and $474 in 2010 with declines in 2011 and 2012 for Medicare, respectively. Commercial patients receiving care in OHS settings consistently faced copayments that were 50 to 100% higher those paid by patients receiving chemotherapy in OBS. Copayment differentials were smaller for Medicare patients. Conclusions: As more patients are receiving care in OHS, these data imply significant financial burdens on patients, especially for those with commercial health insurance. Additional research is necessary to understand the overall cost burden on patients and whether the shift to OHS-based care has negatively impacted patient adherence or quality of life due to financial burden. [Table: see text]
Phase I/II, pharmacokinetic and pharmacodynamic trial of BAY 43–9006 alone in patients with metastatic melanoma
Authors: K. T. Flaherty, M. Redlinger, L. M. Schuchter, C. D. Lathia, B. L. Weber, P. J. O’Dwyer
Journal: Journal of Clinical Oncology (2005)

3037 Background: BAY 43–9006 (BAY) is a novel signaling inhibitor that acts through blockade of the Raf/MEK/ERK pathway at the level of Raf kinase and the receptor tyrosine kinases VEGFR-2 and PDGFR-β. BAY inhibits CRAF and BRAF (wild type/V599E mutant) and inhibits growth of melanoma xenografts. In vitro data indicate that BAY inhibits CYP2C19, CYP2D6 and CYP3A4 with Ki values of 17 μM, 22 μM, and 29 μM, respectively. This phase I/II study was initiated to evaluate the effect of BAY on specific substrates of these enzymes, investigate alterations in tumor perfusion and vascular permeability using dynamic contrast-enhanced (DCE) MRI, and the effect of BAY on kinase activity and gene expression. Methods: BAY was given from day 1 to 28 of a 28-day cycle at 400 mg bid. PK data were collected on Day 28 of the first cycle. Omeprazole, midazolam, and dextromethorphan were administered on day -1 of cycle 1 and day 28 of cycle 1 for evaluation of the effect of BAY administration on known CYP metabolic pathways. Tumor samples were obtained pretreatment for BRAF mutation analysis. DCE-MRI and biopsies of accessible lesions were performed at baseline and after 4 weeks. Response was assessed every 2 cycles using RECIST criteria. Patients (pts) with disease progression on BAY alone could initiate carboplatin/paclitaxel and continue BAY until subsequent progression. Results: 22 melanoma pts (median age 58, PS 0–1) were enrolled. 15 pts received ≥ 1 prior systemic therapy, and 68% had AJCC M1c disease. As in previous studies, BAY was well-tolerated at this dose and schedule. Grade 2/3 toxicities in the first cycle included: hand-foot syndrome (2/0), hypertension (1/0), and pruritus (1/0). There were one PR and 12 SD as best response in 12 patients. Median time to progression was 4 months (range 0–9+). PK, BRAF mutation analysis, MAP kinase pathway activity, and DCE-MRI data are being analyzed. Conclusions: BAY 43–9006 is well-tolerated as a single agent and results in disease stabilization in a subset of patients with melanoma. The relationship of this effect to PK, BRAF mutation status, MAP kinase activity and alterations in tumor blood flow, and the effect of sorafenib on probe substrates of CYP2C19, CYP2D6 and CYP3A4 will be presented. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Bayer Bayer Bayer Bayer Bayer
Comparative evaluation of vibrocompression and bag squeezing: A randomized study
Authors: Letícia Matins, Livia Freitas, Suzilaine Bacci, Lilian Abreu, Lucio Araújo, Célia Lopes
Journal: European Respiratory Journal (2012)

INTRODUCTION:Few scientific evidence has demonstrated the effects of respiratory physiotherapy in intubated children. The clearance maneuvers in mechanical ventilation in this population require further investigation.OBJECTIVES:Analyze and compare the hemodynamic effects, ventilation and respiratory mechanics of two techniques in intubated children with respiratory failure.METHOD:Eleven children with mean age of 28.42±15.42 month were randomized into two groups according to the technique used: (1) Bag Squeezing (BS; n=5) and (2) vibrocompression thoracic (VCT; n=6). All variables were studied before, immediately and 30, 60 and 120min after the maneuvers (p<.05).RESULTS:for both groups were found similar results, no significant differences. Heart rate and mean blood pressure presented higher in BS group in the post maneuver (p=.04, p=.43) compared with pre maneuver. The HR, ETCO2, plateau pressure and static compliance were also higher in the post-maneuver in VCT group. There was no significant difference in the other respiratory variables or respiratory mechanics. Significant negative correlation between Rst e Cst was observed in the BS at all the times evaluated (R=.97,p=.00;R=.89,p=.04;R=.75,p=.00) The same results were observed for VC and ETCO2 post maneuvers (R=.90,p=.03). In the VCT was found positive correlation between the Rst and the Pp before maneuver (R=.97,p=.01),30(R=.94,p=.00) and 120min post (R=.66,p=.00) and between VC and ETCO2. There was also a positive correlation between VC and ETCO2 immediately after maneuver (R=.82,p=.04) and 30 min post (R=.87,p=.02).CONCLUSION:Both techniques didn't present changes in hemodynamic and ventilatory responses, even in the respiratory mechanic.
Are all stage III Wilms tumors the same? Data from the Associazione Italiana Ematologia Oncologia Pediatrica (AIEOP)
Authors: F. Spreafico, L. Piva, P. D'Angelo, M. Terenziani, P. Collini, L. Gandola, M. Bianchi, A. Tamburini, M. Provenzi, F. Fossati Bellani
Journal: Journal of Clinical Oncology (2009)

10030 Background: Criteria to classifying Wilms tumor (WT) as stage III are much heterogeneous, including factors referring both to tumor biology and surgical skills. Methods: We analyzed survival results in patients aged less than 18 years with stage III WT enrolled in the AIEOP CNR92 and TW2003 clinical trials (10/1991–10/2008). Main therapy differences across the trials were the timing of abdominal radiotherapy (RT) (anticipated to 2 nd week from nephrectomy) and doxorubicin cumulative dose reduction from 360 mg/m 2 to 240 in TW2003. Results: Of 553 in-study patients, 106 (19%) were classified as stage III according to NWTS4 criteria (59 patients in CNR92, 47 in TW2003; median age 49 months). Reasons for stage III as follows: lymph nodes (LN) 40 cases (alone 28 cases, combined with other factors 12); cava vein tumor thrombus 7, peritoneum involvement 8, post-operative gross or microscopic tumor remains 24, pre-operative rupture 9, surgical rupture 17. For 29 patients (27%) information on regional LN were missing. 36 patients received primary 4-week vincristine/dactinomycin regimen, while the others had up-front nephrectomy. Adjuvant therapy consisted of 8-months vincristine/dactinomycin/doxorubicin + flank 1440 cGy RT (whole abdominal 15 Gy in case of diffuse peritoneal contamination). 7 patients had intensified chemotherapy/RT for diffuse anaplasia. Interval between nephrectomy and RT was 75 days in CNR92 (median) and 33 in TW2003. Overall 16 tumor failure occurred (2 in anaplastic tumors): abdominal relapse 8 (combined to other extra-abdominal site 3), lung 5, tumor progression 2, metacronous tumor 1. After median follow-up of 49 months 5-year RFS and OS were 83% ±4 and 90% ±3 for the whole cohort of children, respectively. Noteworthy the doxorubicin dose reduction in TW2003 did not jeopardize survival (82% 4-year RFS for CNR92, 84% TW2003). Overall, RFS was 75% ±7 in patients with at least LN involvement compared to 89% ±4 in patients classified as stage III for the remaining criteria, including those without LN sampling (Logrank p.09). Conclusions: The sensible doxorubicin dose reduction did not jeopardize survival. 1440 cGy flank RT warranted satisfactory local tumor control. The worse outcome reported in LN-positive patients deserves further attention. No significant financial relationships to disclose.
Prognostic factors influencing survival of patients with advanced colorectal cancer: hepatic-artery infusion versus systemic intravenous chemotherapy for liver metastases.
Authors: A Y Bedikian, T T Chen, M A Malahy, Y Z Patt, G P Bodey
Journal: Journal of Clinical Oncology (1984)

In this study of 232 patients with histologically confirmed large bowel carcinoma, patient- and tumor-related characteristics were examined and their effect on prognosis was determined. Serum alkaline phosphatase and albumin concentrations, symptom duration prior to diagnosis of the primary tumor, and the status of the primary tumor showed the strongest relationship to survival after diagnosis of surgically noncurable disease. Patients who had normal serum alkaline phosphatase and albumin concentrations, patients whose symptoms lasted over 12 months before diagnosis, and patients whose primary tumor had been resected before diagnosis of noncurable disease had a good prognosis. Performance status, weight loss, sex, presence of liver metastasis, hemoglobin concentration, and absolute lymphocyte or monocyte counts in the peripheral blood, at time of diagnosis of surgically noncurable disease, were significant factors when examined individually. One hundred seventy-nine patients with metastatic colorectal cancer confined to the liver were selected from 601 patients who received chemotherapy for advanced colorectal cancer over 10-year periods to compare the efficacy of hepatic-artery infusion therapy with that of intravenous 5-fluoropyrimidine--containing chemotherapy. The two groups were similar with respect to prognostic factors. The hepatic-artery infusion chemotherapy produced a higher response rate than intravenous chemotherapy, but did not result in significant prolongation of survival.