tbuckley/cabot-search huggingface dataset:
Cancer patients use of nonproven therapy: a 5-year follow-up study.
Authors: T Risberg, E Lund, E Wist, S Kaasa, T Wilsgaard
Journal: Journal of Clinical Oncology (1998)

PURPOSE To investigate the prospective pattern of use of alternative medicine, here called nonproven therapy (NPT), among oncologic patients during a 5-year period, and the relationship between this use and survival, a questionnaire-based follow-up study was performed at the Department of Oncology, University of Tromsø, from 1990 to 1996. PATIENTS AND METHODS Two-hundred fifty-two patients answered the first questionnaire during the period July 1990 to July 1991. Eligible patients were mailed follow-up questionnaires after 4, 12, 24 and 60 months. A telephone interview performed after the last follow-up questionnaire showed little disagreement with the prospective collected information as regards the number of patients reported as users of NPT (kappa, 0.92). RESULTS The number of patients who reported ever using NPT in each cross-sectional part of the study varied between 17.4% and 27.3%. However, the estimated cumulative risk of being a user of NPT during the follow-up period was 45%. Seventy-four percent of NPT users in this north Norwegian study population used faith healing or healing by hand (spiritual NPT) alone or in combination with other forms of NPT. The proportion of patients who used spiritual versus nonspiritual forms of NPT was consistent throughout the follow-up period. Women were more often users than men (50% v 31%, P = .002). Patients older than 75 years of age seldomly used NPT. The 5-year observed survival rate was not influenced by the use of NPT. Adjusted for sex, age, and diagnosis, patients with a high educational level had a borderline higher 5-year survival rate than patients with less education (P = .06). CONCLUSION Our results demonstrate that cross-sectionally designed studies will underestimate the number of ever-users of NPT in a cancer patient population. The use of NPT does not influence observed survival among cancer patients seen in north Norway.
Detection of seven polymorphisms associated with colorectal cancer therapeutic response and toxicity
Authors: K. Z. Qu, Y. Ren, J. Liu, A. Sferrozza, R. A. Bender
Journal: Journal of Clinical Oncology (2006)

13160 Background: First-line therapy for metastatic colorectal cancer (CRC) is 5-fluorouracil/leucovorin in combination with oxaliplatin (ie, FOLFOX™) or irinotecan (ie, FOLFIRI). Optimizing this therapy for an individual patient, however, is complicated due to wide variability in drug response and potential for toxicity. Such variability may be due to functional genomic polymorphisms in the drug target gene or in the metabolizing or DNA repair enzyme genes. We report, herein, development and validation of 2 new assays that, together, detect 7 polymorphisms associated with CRC drug response and toxicity. Methods: The first assay (SNaPshot) simultaneously detects 4 polymorphisms by using primers targeting the ERCC1, XPD, GST-P1, and XRCC-1 genes, single nucleotide primer extension of PCR products, electrophoresis and fluorescent detection on an ABI PRISM® 3100 Genetic Analyzer, and data analysis using GeneMapper® software (Applied Biosystems, Inc.). The second assay (F-PCR) simultaneously detects 3 polymorphisms using paired primers targeting the TS and UGT1A1 genes. One primer per pair is labeled with a fluorescent tag, and electrophoresis, detection, and data analysis are performed as described for the SNaPshot assay. Results: Based on fragment size and color, the intra- and interassay precision for SnaPshot ranged from 0.04%-0.51% and 0.14%-0.59%, respectively, and for F-PCR from 0.02%-0.16% and 0.09%-0.29%, respectively. There was 100% concordance in the genotypes determined in 3 separate SNaPshot (n=44 samples) and F-PCR (n=32 samples) assays. Furthermore, there was 100% agreement between genotypes determined by the SNaPshot method and those determined by RFLP (n=10) and between genotypes determined by the F-PCR method and those determined by pyrosequencing (n=17). Conclusions: Our multiplex SNaPshot and F-PCR methods can accurately detect 7 polymorphisms associated with CRC drug response and toxicity. These multiplex PCRs should lead to improved precision and ease of interpretation relative to that of single PCR methods. These methods may help the clinician optimize CRC therapy for individual patients. No significant financial relationships to disclose.
European view on the pathology of chronic rhinosinusitis, nasal polyposis and the impact of staphylococcal enterotoxins: first results of the Ga2len sinusitis cohort study
Authors: Peter Tomassen, Lars-Olaf Cardell, Natalie De Ruyck, Ulrike Foerster, Wytske Fokkens, Philippe Gevaert, Peter Hellings, Valérie Hox, Elina Katainen, Marek Kowalski, Joaquim Mullol, Heidi Olze, Agnieszka Olzewska, Christine Segboer, Reutherborg A, Elina Toskala, Nicholas Van Bruaene, Cees Van Drunen, Thibaut Van Zele, Claus Bachert
Journal: Allergy (2011)
Mature results of a phase I trial of bortezomib, cisplatin, and radiotherapy for advanced or recurrent head and neck cancer.
Authors: R. S. Axelrod, P. H. Ahn, G. J. Kubicek, P. R. Anne, D. Cognetti, A. Dicker, M. Machtay
Journal: Journal of Clinical Oncology (2010)

5560 Background: Proteasome inhibitor bortezomib (VELCADE) has radiosensitzing properties and preclinical activity against head and neck cancer (HNC). A phase I trial of bortezomib, cisplatin, and radiotherapy (XRT) for advanced or recurrent HNC was conducted. Methods: Eligible patients had locoregionally advanced or recurrent HNC, with disease states for which no standard chemo-XRT regimen exists (e.g. reirradiation or salivary gland cancer). Patients had performance status 0 or 1, good hematologic and renal reserve, and no pre-existing grade >2 peripheral neuropathy. XRT was given once daily for at least 2 weeks. Cisplatin was given once weekly at 30 mg/m2/wk. Bortezomib was given on days 1, 4, 8, and 11 of a 21-day cycle, starting day 1 of XRT. The initial starting dose of bortezomib was 0.7 mg/m2, with planned escalation levels of 1.0 mg/m2 and 1.3 mg/m2. Dose escalation was performed after patients at the previous dose level were assessed > 30 days to rule out any dose limiting toxicity (DLTs), defined as grade 4-5 toxicity or grade 3 toxicity attributable to bortezomib that required hospitalization. Results: 27 patients with previously untreated local-regionally advanced (10 patients) or recurrent/previously irradiated (17 patients) HNC were enrolled. All patients completed XRT as planned (median 60.8 Gy); the median number of doses of bortezomib received was 7. There were no grade 5 toxicities. There were no DLTs in 7 patients enrolled in dose level I (0.7 mg/m2), and one DLT of grade 4 neutropenia in 10 patients enrolled in dose level II (1.0 mg/m2; re-irradiation). In dose level III (1.3 mg/m2), 2 DLT's occurred in 10 patients (asymptomatic grade 4 thrombocytopenia, both re-irradiation). grade 3 toxicities were common at all dose levels (17 of 27 evaluable patients), with most attributable to XRT/cisplatin (e.g. mucositis) and not considered DLTs. There was no clinically significant peripheral neuropathy (grade >2). At a median 7.3 month follow-up, 8 patients (30%) are without progression. Conclusions: Bortezomib in combination with XRT and weekly cisplatin is feasible and active. MTD was reached at 1.3 mg/m2 for radiation-naive patients and 1.0 mg/m2for re-irradiation patients. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Millennium
Phase I/II study of the combination of decitabine (DAC) and temozolomide (TMZ) in patients (pts) with metastatic melanoma (MM).
Authors: H. A. Tawbi, J. H. Beumer, A. A. Tarhini, S. J. Moschos, M. J. Egorin, S. C. Buch, Y. Lin, J. M. Kirkwood
Journal: Journal of Clinical Oncology (2010)

8533 Background: TMZ has clinical activity at least equal to that of dacarbazine in MM. The DNA repair protein, O6- methylguanine-DNA-methyltransferase (MGMT), is implicated in resistance to TMZ. A functional DNA mismatch repair (MMR) pathway is required to initiate TMZ-induced cell death; MMR deficiency induced by promoter hypermethylation is a known mechanism of resistance. We hypothesized that combining of TMZ with DAC will induce dual modulation of DNA repair by depleting MGMT and re-expressing MMR. We now report results of a phase I/II study of TMZ and DAC in MM. Methods: In the phase I portion, pts were treated on 2 DAC dose levels (DL): 0.075 mg/kg IV qd and 0.15 mg/kg IV qd. DAC was administered qd × 5 d/wk for 2 wks, and TMZ was administered PO at 75 mg/m2 qd for 4 wks, starting on wk 2 of a 6-wk cycle. Phase II used a Simon 2-stage design: 14 eligible pts were to be accrued, and if ≥ 1 objective response (OR) was observed, the study would accrue an additional 20 pts. PK sampling was performed on Days 1 and 8; PBMC and tumor tissues were obtained on Days 1, 8, 15 and 29 of cycle 1. Results: 4 pts (3 evaluable) were accrued to DL1, and no DLTs were observed. There were no DLTs in the 6 pts accrued to DL2, which was declared the recommended Phase II dose (RP2D). 13 pts (12 evaluable) have been accrued to the Phase II portion, 1 PR has been observed, and the trial has proceeded to full accrual. Of the 18 pts treated at the RP2D, 9 (50%) have had stable disease for > 12 wks and continue to be on treatment. 3 (17%) have had SD > 24 wks. Grade ¾ neutropenia has been observed in 61% of pts but was reversible and in only 1 pt lasted > 7 d. 2 episodes of febrile neutropenia have been observed in the 18 pts at the RP2D. Serial tumor biopsies obtained from 2 pts confirmed the hypomethylating effect of DAC in melanoma. Conclusions: The combination of DAC and TMZ can be administered safely at biologically relevant dosages. The dual DNA repair modulation approach to the abrogation of chemotherapy resistance appears promising. Accrual is ongoing and will be completed by March 2010. Support: Eisai, Inc., Schering-Plough Research Institute, and University of Pittsburgh Cancer Institute, Melanoma and Skin Cancer Program P50 CA121973. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Eisai, Schering-Plough Research Institute
Phase I study of the safety, tolerability, and pharmacokinetics (PK) of weekly paclitaxel administered in combination with pazopanib (GW786034)
Authors: A. R. Tan, S. F. Jones, A. Dowlati, K. Levinson, K. Beatty, B. Suttle, D. Gibson, T. Arumugham, J. Lager, H. A. Burris
Journal: Journal of Clinical Oncology (2008)

3552 Background: Pazopanib is an oral angiogenesis inhibitor targeting VEGFR, PDGFR, and c-kit with demonstrated activity in renal cell cancer, sarcoma, and ovarian cancer when administered at 800 mg daily. Improved efficacy of weekly paclitaxel with the anti-VEGF agent bevacizumab in metastatic breast cancer provides a rationale for combining an angiogenesis inhibitor with a taxane. Methods: Patients (pts) with advanced cancer (ECOG PS 0–1) were eligible. Dose escalations of paclitaxel (15–80 mg/m2) on days 1, 8, 15 q 28 days plus pazopanib (400–800 mg) daily were evaluated for safety, PK, and clinical response. Dose escalation occurred in cohorts of 3–6 pts based on dose-limiting toxicities (DLTs) and PK; the optimally tolerated regimen (OTR) consisted of ≤ 1/6 pts experiencing a DLT; 9 additional pts were enrolled to confirm the OTR. Results: 25 pts received paclitaxel/pazopanib at doses of 15/400 (3), 15/800 (3), 50/800 (3) and 80/800 (16) mg. Median age was 58 y; M: 48%; 92% Caucasian. Most common tumor types were breast (5), CRC (3), esophageal (3), and NSCLC (3). Most frequent adverse events (AEs) (mostly Gr 1/2) were nausea (68%), fatigue (56%), diarrhea (52%), vomiting (48%), rash (44%), anorexia (32%), visual disturbance (24%), alopecia (24%), and constipation (24%). Hepatic enzyme elevations: ALT (48%), AST (44%), alkaline phosphatase (24%), and bilirubin (12%) were mainly Gr 1/2. The OTR was defined as 80 mg/m2 paclitaxel and 800 mg pazopanib (median 2.5 cycles [range 1–8]; median no. of 2 prior regimens [range 1–5]); 1 DLT (Gr 3 groin abscess) was observed at this dose. 12/16 pts at the OTR required dose modifications; 3 of these were withdrawn due to an AE. For pazopanib, 7 pts required interruptions and 3 pts required dose reductions. For paclitaxel, 11 pts required interruptions/delays and 5 pts required dose reductions. Liver enzyme elevation was the most common reason for dose modification. Pazopanib increased mean paclitaxel AUC (45%) and Cmax (40%). Clinical activity at the OTR: PR in 5/16 (31%) pts and SD > 8 wks in 10/16 (63%) pts. Conclusions: Therapeutic doses of daily pazopanib and weekly paclitaxel can be combined with a manageable toxicity profile and evidence of clinical activity. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration GlaxoSmithKline GlaxoSmithKline Eli Lilly, Genentech™ BioOncology Aventis, Celgene, GlaxoSmithKline, OSI Oncology
Predictive factor for residual tumor after lumpectomy for close margins
Authors: V. Ozmen, S. Ozkan Gurdal, M. Muslumanoglu, A. Igci, S. S. Tuzlali, B. Ozcinar, E. Canbay, M. Kecer, T. Dagoglu
Journal: Journal of Clinical Oncology (2009)

e11538 Background: It is critical to obtain clear margins to minimize local recurrence after breast conserving surgery(BCS). When re-excisions are performed, there is often no residual disease in the new specimen, calling into question the need for re-excision(s) or mastectomy. The aim of the present study was to identify factors predicting a histologically positive re-excision specimen. Methods: Our prospective breast cancer database was queried for all invasive breast cancer patients who underwent a re-excision lumpectomy for either close or positive margins after an attempt at BCS. Close margins are defined as ≤ 2 mm for invasive carcinoma and presence of ductal carcinoma in situ(DCIS). Clinicopathologic features were correlated with the presence of residual disease in the re-excision specimen. Results: Between February 1997 and August 2008, 2054 patients with early breast cancer underwent surgical treatment in our breast unit. 939(45.7%) of them had BCS. In 543 patients(26.4%), re-excision required due to close margins on the permanent section analysis of their initial surgical specimens. 186 patients(34.3%) had previous excisional biopsy in other clinics. Median age of 543 patients was 50 years. In 290 patients(53.4%), mastectomy was performed due to positive surgical margin or poor cosmetic results. There were no residual tumors in re-excision(65.6 %) or mastectomy(42.4%) specimens of patients. The factors associated with tumor positive re-excision specimen were, age ≤50 years(p=0.044), lymphovascular invasion (p=0.029), multifocality(p&lt;0.001), tumor size &gt;2cm(p=0.008), presence of DCIS(p=0.018), focal margin positivity(p&lt;0.001), DCIS at resection margin(p=0.008) and node positivity (p&lt;0.001). Conclusions: Most of our patients with early breast cancer had unnecessary re-excisions or mastectomy to obtain clear surgical margins. In subset group of patients, re-excision or mastectomy may not be required. No significant financial relationships to disclose.
Preoperative Chemoradiation in an Era of Suboptimal Clinical Staging
Authors: Wayne L. Hofstetter
Journal: JAMA Surgery (2015)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Surgery HomeNew OnlineCurrent IssueFor Authors Podcast Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Surgery journal
An analysis of the effect of smoking status on erlotinib pharmacokinetics (PKs), toxicity, and ability to dose escalate in a phase II study of erlotinib in advanced pancreatic cancer (PC).
Authors: D. J. Renouf, P. A. Tang, E. X. Chen, R. Ho, L. Lourenco, L. Wang, M. J. Moore
Journal: Journal of Clinical Oncology (2010)

4056 Background: OSI-Tar 725 is a phase II study assessing the efficacy of erlotinib, dosed to achieve a rash, in patients (pts) with advanced PC. Smoking may alter erlotinib PKs through induction of CYP1A1/1A2. We examined the effect of smoking on erlotinib PKs, toxicity, and ability to dose escalate. Methods: Erlotinib was given at an initial dose of 150 mg/day to eligible pts with locally advanced (LA) or metastatic PC who had progressed or were unable to tolerate gemcitabine-based chemotherapy. Erlotinib dose was increased by 50mg every 2 weeks (maximum 300 mg/day) until ≥ grade 1 rash (CTCAE v 3.0) or other dose-limiting toxicities occurred. Steady-state erlotinib plasma concentrations were determined on cycle 1, day 1 and 14, pre-dose (Cmin). Detailed baseline smoking status was obtained. The primary endpoint of this two-stage phase II trial was prolonged disease control (partial response and/or stable disease > 8 weeks). Results: 50 pts were accrued (median age 61, M:F = 25:25, ECOG 0:1:2 = 5:41:4, LA:metastatic = 5:45). Smoking status was obtained in 46 pts; 5 were current smokers (CS), 25 were past smokers (PS), and 16 were never smokers (NS). PK data were available from 30 pts with known smoking status (4 CS, 17 PS, 9 NS). The mean erlotinib Cmin on day 14 in CS, PS and NS was 517 ng/mL, 1,008 ng/mL and 1,862 ng/mL respectively (p = 0.01 for CS vs. NS, p = 0.01 for PS vs. NS). The mean Cmin of the main active metabolite of erlotinib (OSI-420) on day 14 in CS, PS and NS was 55 ng/mL, 123 ng/mL, and 256 ng/mL respectively (p = 0.01 for CS vs. NS, p=0.03 for PS vs. NS). Cycle 1 ≥ grade 2 diarrhea or rash occurred in 0/5 (0%) CS, 8/25 (32%) PS, and 7/16 (44%) NS (p = 0.12 for CS vs. NS). Dose reduction due to ≥ grade 3 toxicity was necessary in 0/5 (0%) CS, 2/25 (8%) PS, and 0/16 (0%) NS. Of the pts that remained on study for ≥ 2 weeks, 3/4 (75%) CS, 7/24 PS (29%), and 0/14 (0%) NS underwent dose escalation (p = 0.005 for CS vs. NS). Conclusions: Smoking status is associated with erlotinib plasma concentrations, and was predictive of toxicity and ability to dose escalate in this study. Differential upfront dosing of erlotinib in PC based on smoking status should be further evaluated. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration OSI OSI
Brief Communication: Identification of PhI Chromosome and Associated Translocation in Chronic Myelogenous Leukemia by Hoechst 332582
Authors: T. Raposa, A. T. Natarajan, I. Granberg
Journal: JNCI Journal of the National Cancer Institute (1974)

Journal Article Brief Communication: Identification of PhI Chromosome and Associated Translocation in Chronic Myelogenous Leukemia by Hoechst 33258 Get access T. Raposa, T. Raposa Search for other works by this author on: Oxford Academic PubMed Google Scholar A. T. Natarajan, A. T. Natarajan 4 4Address reprint requests to: Dr. A. T. Natarajan, Wallenberg Laboratory, Lilla Frescati, S 10405 Stockholm 50. Search for other works by this author on: Oxford Academic PubMed Google Scholar I. Granberg I. Granberg Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 52, Issue 6, June 1974, Pages 1935–1938, https://doi.org/10.1093/jnci/52.6.1935 Published: 01 June 1974 Article history Received: 28 December 1973 Accepted: 30 January 1974 Published: 01 June 1974
Effects of a proton pump inhibitor (lansoprazole) and food on the bioavailability of enzastaurin administered as single oral doses to healthy subjects
Authors: P. Welch, L. Musib, C. Darstein, J. Baldwin, M. Ayan-Oshodi
Journal: Journal of Clinical Oncology (2007)

14076 Background: Enzastaurin (ENZ) targets the PKCβ and PI3K/AKT pathways to induce tumor cell apoptosis, reduce proliferation, and suppress tumor-induced angiogenesis. In vitro studies show ENZ solubility is highest at pH 2.0 and decreases with increasing pH. This study examined the effect of increased gastric pH by a proton pump inhibitor (lansoprazole) and the effect of food on the bioavailability of a single oral dose of ENZ in healthy subjects. Methods: In this open-label, three-period, fixed sequence, crossover study, healthy subjects received an oral, 500-mg single dose of ENZ in the fed state, alone (A) and with lansoprazole (B), and in the fasted state alone (C). Lansoprazole was dosed for 5 days, with ENZ administered 2 hours after the 5 th dose. A two-week washout occurred between each period. Plasma samples were collected at predose and scheduled timepoints for up to 168 hours post-ENZ dose for pharmacokinetic (PK) characterization of ENZ and its active metabolites. Results: 22 subjects were enrolled in the study with 19 subjects completing all treatment periods. The table summarizes the PK results for enzastaurin and total analytes (enzastaurin + metabolites). ENZ C max and AUC (0–8) were unaffected by the administration of lansoprazole, when ENZ was then given in the fed state. Enzastaurin C max and AUC (0–8) increased significantly, respectively by 6.8 and 2.8 fold, when ENZ was administered after a standardized breakfast, compared to the fasted state. Median t max increased from approximately 3 hours in the fed state to 6 hours in the fasted state, indicating slower absorption when ENZ was administered in the fasted state. Conclusions: No significant alterations in ENZ exposures were seen in the presence of lansoprazole, indicating that increased gastric pH did not decrease exposures of ENZ, when ENZ is administered in the fed state. Exposures of ENZ and its active metabolites were significantly enhanced by administration of ENZ after a meal. [Table: see text] No significant financial relationships to disclose.