tbuckley/cabot-search huggingface dataset:
Difference between skin toxicities in erlotinib (E) and gefitinib (G) in the treatment of advanced non-small cell lung cancer (NSCLC)
Authors: C. Defferrari, M. Loprevite, A. Brianti, G. Catania, F. Grossi, P. Pronzato
Journal: Journal of Clinical Oncology (2007)

18187 Background: Cutaneous toxicities due to E or G are common and reversible adverse effects. In the two large randomized trials with E (Shepherd F et al, NEJM 2005) and G (Thatcher N et al, Lancet 2005) skin rash toxicity incidence seems different between the two drugs: all grades (gr) were observed in 76% and 37% of patients (pts), gr 3–4 in 9% and 2% respectively. The aim of this study was to assess the incidence of the most common toxicities occurred in a cohort of pts treated with E or G in the same period of time and evaluated by the same medical staff according to the Common Toxicity Criteria version 3.0. Methods: From May 2005 to July 2006, 47 pts suitable for a treatment with an EGFR inhibitor were evaluated for their eligibility in an open label phase II trial with E 150 mg/day. Pts ineligible for the latter (16) were treated with G 250 mg/day in a compassionate-use program. Fifteen pts were treated with G at progression after E. Results: Toxicities (all gr, gr 3/3–4) for E vs G consisted in: acneiform rash (64 vs 25%, 13 vs 0%), rash/desquamation (83 vs 19%, 12 vs 0%), pruritus (38 vs 16%, 6 vs 0%), dry skin (48 vs 32%, 3 vs 0%), nail changes (15 vs 6%, 3 vs 0%), diarrhea (54 vs 19%). When pts were treated with both E and G the toxicities (all gr, gr 3/3–4) observed were: acneiform rash (93 vs 20%, 27 vs 0%), rash/desquamation (100 vs 20%, 20 vs 0%), pruritus (41 vs 13%, 7 vs 0%), dry skin (54 vs 27%, 7 vs 0%), nail changes (27 vs 7%, 7 vs 0%), diarrhea (53 vs 7%). Conclusions: Our data are not conclusive being a non-randomized trial. However, these results suggest that there are less cutaneous adverse effects with G. This difference may be probably attributed either to the dose or the bioavailability of E. No significant financial relationships to disclose.
The pharmacogenetic effect of ADRB2 polymorphisms on therapeutic response in COPD
Authors: Malika Mustafina, Olga Tsvetkova, Eduard Generozov
Journal: European Respiratory Journal (2012)

Background   Most pharmacogenetics studies of COPD have focused on the role of variants in the b2-adrenergic receptor gene on bronchodilator response, but the findings have been inconclusive.   Objective   To investigate lung function responses following a 24-week treatment with a long-acting b2 agonist combined with a steroid inhaler in patients with COPD with various ADRB2 genotypes.    Methods   In 73 patients with stable COPD, polymorphisms in the amino acid position 16 (Arg16/Gly16) and 27 (Gln27/Glu27) of the ADRB2 gene were assessed by allele-specific polymerase chain reaction. Long-term response was evaluated using observed change in spirometric values before and after the treatment with formoterol (12 ug) combined with budesonide (400 ug) inhalation twice daily for 24-week.   Results   In terms of codon 16 variants, the FEV1 changes following the 24-week treatment were 5.64 ± 1.49% predicted in Gly/Gly patients, -3.40 ± 0.85% predicted in Arg/Gly patients, and -7.00 ± 1.38% predicted in Arg/Arg patients (p    Conclusion   Arg16-Gln27 haplotype was associated with decreased lung function after 24-week treatment with long-acting β2-agonists plus inhaled corticosteroids in a Russian population.
Thymidylate synthase (TS) and methylenetetrahydrofolate reductase (MTHFR) gene polymorphisms: Relationships with capecitabine (X) pharmacodynamics in advanced breast cancer (ABC) patients (pts)
Authors: R. Largillier, J. L. Formento, A. Ginot, M. C. Etienne, M. Francoual, N. Renée, J. M. Ferrero, C. Foa, M. Namer, G. Milano
Journal: Journal of Clinical Oncology (2004)

2062 Background: TS expression and reduced folate levels significantly influence fluoropyrimidine pharmacodynamics. X is a highly effective oral fluoropyrimidine carbamate with proven single agent activity for the treatment of ABC, which improves survival when added to docetaxel. We prospectively analyzed the impact of gene polymorphisms potentially linked to TS expression and 5–10 methylenetetrahydrofolate concentrations (MTHFR gene) on toxicity and response in X-treated ABC pts. Methods: TS gene polymorphisms in the 5' (28 base pair tandem repeats) and 3' (6 base pair deletion) regions were analyzed by PCR. C677T and A1298C MTHFR gene polymorphisms were determined by melting curve analyses (LightCycler). We analyzed DNA from mononuclear cells of 57 pts with ABC, median age 57 (36–79), 60% multiple metastatic sites, prior treatment: 88% anthracycline, 70% taxane and 21% 5-FU, current treatment setting: 21% pts first, 47% second line. Mean initial dose of X was 1048 mg/m2 twice-daily d1–14 every 3 weeks, median number of cycles 7 (1–15). Results: 3'TS genotype (26 pts 110/110, 27 pts 104/110, 4 pts 104/104), C677T MTHFR genotype (22 pts wt/wt, 24 pts wt/mut, 11 pts mut/mut) and A1298C MTHFR genotype (33 pts wt/wt, 19 pts wt/mut, 5 pts mut/mut) were not correlated to any X-related toxicities (WHO criteria grade 0–1 vs 2–4 at 1st cycle). In contrast, 5'TS genotype (11 pts 2R2R, 23 pts 2R3R, 21 pts 3R3R) was significantly linked to hand-foot syndrome and nausea-vomiting (Fisher's Exact test: both p = 0.03). 3R3R pts had less toxicity. Response to treatment was assessed after the 3rd cycle (21% progression, 50% stabilization, 27% partial, 2% complete responses). Clinical benefit (i.e. stabilization or response vs progression) was not linked to any TS or MTHFR gene polymorphisms. Conclusion: Constitutional TS polymorphism in the 5' region may be predictive of X pharmacodynamics, but needs confirmation in a prospective study. Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Hoffmann-La Roche Hoffmann-La Roche Hoffmann-La Roche
BMJ paper wins Ig Nobel award for speed bump diagnosis of appendicitis
Authors: Janice Hopkins Tanne
Journal: BMJ (2015)

The 2015 Ig Nobel award for Diagnostic Medicine, for a study showing that pain while travelling over speed bumps is a sign of acute appendicitis, was presented to Helen Ashdown and her UK team on 17 September at the awards’ 25th annual ceremony, held at Harvard University in Cambridge, Massachusetts, USA.

The paper, by Ashdown and a team from the University of Oxford and Stoke Mandeville Hospital was published in The BMJ in 2012.1 It is the fourth BMJ paper to win an Ig Nobel award in recent years.2 3 4 The Ig Nobel awards honour achievements that first make people laugh and then make them think.

Ashdown, dressed as a speed bump and wearing a traffic cone for a hat, lay down on the Harvard stage while colleagues stepped over her and mimicked the effect on a person with appendicitis of passing over a speed bump. She told The BMJ that doctors had commented that patients with possible appendicitis often said that the pain was worse when their transport passed over speed bumps.

“I’m interested in evidence based medicine,” said …
TCT-742 Catheter Ablation of Ventricular Tachycardia in Patients with Structural Heart Disease – A Meta-analysis
Authors: Arun K. Kanmanthareddy, Avanija R. Buddam, Madhu Reddy, Mahesh Anantha Narayanan, Vivek Yarlagadda, Venkata M. Alla, Claire Hunter, Dhanunjaya Lakkireddy
Journal: Journal of the American College of Cardiology (2015)
HER2 genetic polymorphism and pharmacodynamics of trastuzumab-based treatment in breast cancer patients
Authors: G. A. Milano, W. Lescaut, J. L. Formento, R. Largillier, M. Campone, E. Chamorey, M. Francoual, J. M. Ferrero
Journal: Journal of Clinical Oncology (2005)

501 Background: A single SNP at codon 655 (Val655Ile) in the transmembrane domain of HER2 gene was shown to be associated with an increased risk of breast cancer (Xie et al, J Natl Cancer Inst, 2000). A model for the activation of HER2 suggests that this Val/Ile substitution could destabilize the formation of active HER2 dimers (Fleishman et al, PNAS, 2002). These findings led us to explore the possible association between HER2 genotype and the pharmacodynamics of HER2 targeting therapy with Herceptin. Methods: Genomic DNA from 57 consecutive advanced breast cancer patients (mean 57 years, 33–83) receiving a herceptin-based treatment (combined with paclitaxel for the majority) were examined for the Val655Ile polymorphism with a PCR-RFLP based assay. Results: The genotype repartition (%) was 7 for ValVal, 36.9 for Ile/Val and 56.1 for Ile/Ile. There was no significant link between HER2 genotype and objective response rate (66% for Val/Ile + Val/Val and 65% for Ile/Ile), disease-free survival (median, months: 21 for Val/Ile + Val/Val and 18 for Ile/Ile) and overall survival (median, months: not reached for Val/Ile + Val/Val and 48 for Ile/Ile). Of note, there were 5 cases of herceptin-linked cardiotoxicity and all these patients carried the Val allele (p=0.008). Conclusion: These results suggest for the first time a potential clinical value for HER2 genetic polymorphism in the management of herceptin-based treatment.
Cyclin D1 polymorphism and cervical cancer risk
Authors: Y.-T. Jeon, J. W. Kim, N.-H. Park, Y.-S. Song, S.-B. Kang, H.-P. Lee
Journal: Journal of Clinical Oncology (2004)

5050 Background: It is proposed that the cyclin D1 is to serve as an active switch in the regulation of continued cell cycle progression. Though many investigators have reported a relationship between the A/G870 polymorphism in exon 4 of the cyclin D1 gene and the susceptibility to carcinomas of various origins, there are few reports of that in cervical cancer. Our aim was to investigate the association of cyclin D1 single nucleotide polymorphism with susceptibility to cervical cancer in Korean women. Methods: The study was carried on 233 cervical cancer patients (cases) and 334 patients with benign disease (controls) who received surgical treatment at Seoul National University Hospital. By polymerase chain reaction and restriction fragment length polymorphism method, cyclin D1 genotyping was carried out. Results: Of the 233 cervical cancer patients, 186 (79.8%) had squamous cell carcinoma and 47 (20.2%) had other cell types of carcimoma. The analysis of the cases showed that the allelic and genotypic frequencies were similar in the patients with squamous cell carcinoma and those with other types of carcinoma. However the allelic frequencies of the cases (A, 0.54; G, 0.46) were significantly different from those of the controls (A, 0.49; G, 0.51) (p = 0.025). The G/G genotype was significantly less frequent among cases (6.9%) than among controls (16.2%) (p = 0.001). The regression analysis after adjusting for age showed that the A/G and A/A genotype had 3.02 (95% confidence interval [CI] = 1.54–5.93) and 2.44 (CI = 1.33–4.47) times increased risk for the development of cervical cancer compared to the G/G genotype. When analyzed with combining the A/G and A/A genotype, A/G + A/A genotype had 2.57 (CI = 1.42–4.67) times increased risk for the cervical cancer compared to the G/G genotype. Conclusions: Determination of the cyclin D1 single nucleotide polymorphism may be applicable to identify individuals with increased risk for cervical cancer in Korean women. No significant financial relationships to disclose.
Acridine Orange-DNA Complex in Actinic Keratosis2
Authors: Masanobu Kumakiri, Ken Hashimoto
Journal: JNCI Journal of the National Cancer Institute (1977)

Electron microscopy processing and staining of nuclei were used to localize reaction products of acridine orange staining in actinic keratosis of human skin. Electron-dense granules about 10-100 nm in diameter were seen exclusively in the euchromatin portion of the nucleus. Almost all tumor cells had granules (mean = 65; SD = 26). These granules were also occasionally observed in the dermal connective tissue cells in the lesion. However, the mean number of 10 granules seen in these cells was definitely less than that of tumor cells. Normal skin controls did not have granules except occasionally in the basal cells of the epidermis.
Final results of a multicenter phase II study of irinotecan (CPT-11) in patients (pts) with advanced hepatocellular carcinoma (HCC)
Authors: V. Boige, J. Taieb, M. Hebbar, E. Magherini, D. Mignard, T. Debaere, L. Hannoun, J.-M. Tigaud, M. Ducreux
Journal: Journal of Clinical Oncology (2004)

4180 Background: The objective of this study was to determine the efficacy and safety of CPT-11 as a single agent in pts with HCC. Because chronic liver dysfunction is frequently observed in these pts, CPT-11 dose was adjusted to bilirubin, according to the results of our previous phase I study on CPT-11 in pts with hyperbilirubinemia. Methods: The primary endpoint was the response rate of CPT-11 in pts with HCC not candidates for surgical resection or percutaneous destruction. Pts with multifocal HCC, no prior systemic chemotherapy, PS ≤ 2, adequate renal and bone marrow function, and bilirubin ≤ 3xUNL, were enrolled. Pts in group A (bilirubin ≤1.5xUNL) and group B (bilirubin 1.5 to 3.0xUNL) received i.v. CPT-11 at 350 mg/m2, and 200 mg/m2 respectively, over 30 to 90 min, q3w. Tumor response was evaluated by CT scan or RMN coupled with α–foetoprotein dosage every 3 courses. Results: 29 pts (23 in group A, 6 in group B) were included: median age = 59 [24–76], sex ratio (M/F) = 24 / 5; PS 0/1/2 = 14/12/2 (1 ND). A total of 130 cycles (group A: 111; group B: 19) were delivered (median = 3 [1–13]). Hematological grade 3–4 toxicities by pt (group A/group B) consisted in neutropenia (48% / 17%) and febrile neutropenia (13% / 0%), anemia (22% / 33%). Non hematological toxicities by pt were: vomiting (8% / 0%), diarrhea (22% / 0%), hepatic cytolysis (4% / 0%) asthenia (17% / 0%). One 1 MR (group A), 13 SD (group A:10 / group B:3) and 11 PD (group A:9 / group B:2) were observed among the 25 evaluable pts for efficacy. Overall survival was 7.4 in months [95%CI 3.9–12.0]. Median time to progression was 3.7 months [95%CI 2.1–4.0]. Tumor growth control lasted 4.0 months [95%CI 3.8–7.1] Conclusions: In pts with unresectable HCC, CPT-11 adjusted to bilirubinemia is feasible in pts with liver dysfunction and achieved 56% disease control in poor prognosis patients. Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Laboratoire Aventis Laboratoire Aventis Laboratoire Aventis
Fgfr Inhibitor and Chemotherapy in Gastric Cancer (Facing): Phase I Results from an Ecmc Combinations Alliance Phase I/II Trial of Azd4547 in Combination with Cisplatin and Capecitabine (Cx)
Authors: C. Lindsay, F. Thistlethwaite, A. Gupta, W. Mansoor, L. Lewsley, R. Hubner, C.A. Hopkins, K. Chan, C. McDowell, S. Campbell, L. Douglas, C. Bray, M. Ranson, C. Dive, M.R. Middleton, D. Landers, T.R..J. Evans
Journal: Annals of Oncology (2014)
Clinicopathological study of brain metastases in breast cancer patients treated with or without trastuzumab
Authors: Y. Saito, Y. Tokuda, Y. Suzuki, S. Umemura, R. Y. Osamura
Journal: Journal of Clinical Oncology (2005)

693 Background: Trastuzumab plays the important role in the treatment of patients with HER2 overexpressing metastatic breast cancer. Since its introduction into the treatment strategy of metastatic breast cancer, brain metastases during trastuzumab therapy have been frequently observed. Only a few studies have compared the risk of brain metastases in patients treated with or without trastuzumab. Methods: We conducted the retrospective and clinicopathological study of the fifty-seven patients with brain metastases treated in our hospital between 1989 and 2003. Those fourteen patients with brain metastases were surgically removed to be pathologically compared with primary tumors. Results: Twenty-seven patients were positive for HER2, while the remaining thirty patients were negative. The time from the first recurrence to brain metastases and the median overall survival time were not significantly different between HER2 positive and negative patients. Nineteen patients were treated with the trastuzumab-based therapy out of twenty seven HER2 positive patients. The time from the first recurrence to brain metastases was 17.4months for those patients who received trastuzumab-based therapy, while 8.3 months for the patients who did not receive trastuzumab (p<0.01). The survival period after brain metastases was 9.8months for the patients who received trastuzumab, while 1.1 months for the patients who did not receive trastuzumab (p<0.01). The median overall survival period was 51.8 month for those patients who received trastuzumab and 34.4 months for the patients who did not received trastuzumab(p<0.01). The fourteen tumors of the brain had the same HER2 status to primary tumors, except one tumor changed negative. Conclusions: This study showed that trastuzumab patients with brain metastases have survived significantly longer interval after first recurrence and the development of brain metastases, when comparing with control group. No significant financial relationships to disclose.
Treatment outcome and survival for patients (pts) with sarcomatoid-variant metastatic renal cell carcinoma (RCC): Memorial Sloan-Kettering Cancer Center (MSKCC) experience
Authors: A. M. Molina, S. K. Tickoo, N. Ishill, M. J. Trinos, L. H. Schwartz, P. Russo, D. R. Feldman, S. Patil, R. J. Motzer
Journal: Journal of Clinical Oncology (2009)

e16017 Background: Sarcomatoid-variant represents a spindle cell phenotype of RCC that can be present in any subtype, usually showing aggressive biological behavior. MSKCC experience was studied to provide data on outcome and survival to systemic therapy for metastatic, sarcomatoid-variant RCC. Methods: Clinical features, treatment outcome and survival were reviewed in 63 pts with sarcomatoid-variant metastatic RCC from a database of 650 pts treated at MSKCC with systemic therapy (cytokines, anti-angiogenesis targeted therapy and chemotherapy). Response to therapy, progression-free survival (PFS), and overall survival (OS) was determined for pts based on their first treatment at MSKCC. The percentage of sarcomatoid component in the tumors was assessed. Results: Histology subtypes with sarcomatoid-variant among the 63 pts included 46 clear cell, 5 papillary, 5 chromophobe, 1 collecting duct, and 6 unclassified. 60 pts had prior nephrectomy. MSKCC risk group distribution was 37% good risk, 59% intermediate risk, and 5% poor risk. 34 pts received targeted therapy (29 sunitinib, 3 sorafenib, 2 temsirolimus), 20 pts received cytokine therapy (19 interferon, 1 interleukin) and 9 received other therapies. 5/63 pts achieved an objective response: 1/19 to interferon and 4/29 to sunitinib. In 63 pts, median PFS was 3 months (95% CI 2–4) and median OS was 10 months (95% CI 8–14). Differences in PFS were observed based on therapy (sunitinib vs. all other) and histology (clear cell vs. non-clear cell). The median PFS for sunitinib therapy was 4.4 months (95% CI 2.2–6.7) versus 2 months (95% CI 1.7–2.7) for all other therapies (p = 0.02); and 3 months (95% CI 2.3–4.5) for clear cell versus 1.6 months (95% CI 1.0–2.1) for non-clear cell histology (p = 0.007). In a subset (n = 31) with available specimen, the median % sarcomatoid content was 20% (range 2%-100%). No difference in PFS or OS was observed according to % sarcomatoid content. Conclusions: Metastatic sarcomatoid-variant RCC is associated with a poor prognosis. Sunitinib resulted in a modest response rate and longer PFS versus other therapies. Studies to assess outcome, characterize tumor biology, and develop novel treatment strategies are warranted. [Table: see text]
健常者肺繊維芽細胞においてIFN‐ガンマ効果を軽減するIL‐10相補DNAトランスフェクション
Authors: Hashimoto T, Oshika Y, Yamazaki H, Nakamura M, Ueyama Y, Ota H, Minoguchi K, Adachi M
Journal: Journal of Allergy and Clinical Immunology (2000)
Phase II trial of satraplatin and paclitaxel in the first-line treatment of advanced non-small cell lung cancer
Authors: D. Shipley, D. R. Spigel, C. Cavanaugh, Y. Moore, J. D. Hainsworth, S. Jones, H. A. Burris, L. Sade, D. A. Yardley, F. Greco
Journal: Journal of Clinical Oncology (2007)

18073 Background: Satraplatin (S) is a novel oral platinum analogue that has shown promising activity in a number of solid tumor settings. Our center previously conducted a phase I trial combining S and paclitaxel (P) in patients (pts) with refractory malignancies, establishing safety for this combination. This single center community-based trial was designed to examine the role of S/P in pts with newly diagnosed advanced non-small cell lung cancer (NSCLC). Methods: The primary endpoint is the objective response rate (ORR). Eligibility criteria: newly diagnosed and unresectable stage IIIB/IV NSCLC, measurable disease, ECOG PS 0–2, and informed consent. Treatment: S 80 mg/m 2 PO days 1–5 and P 200mg/m 2 IV day 1, every 28 days for a maximum of 6 cycles. Pts were restaged every 8 weeks. Results: 28 pts were enrolled from 2/06 to 12/06 (trial ongoing, n = 40 planned). Data are available on 24 pts for analysis. Baseline characteristics: median age 67 years; male/female, 58%/42%; and ECOG PS 0/1/2, 25%/63%/12%; adenocarcinoma/squamous/large cell/unspecified, 33%/42%/1%/24%. The ORR was 17% (95% CI 5%-37%). 10 pts (42%) had stable disease (SD) and 5 pts (21%) had progressive disease. The disease control rate (ORR + SD) was 59%. 5 pts were not evaluable due to: death (3 pts - 1 possibly due to treatment- related sepsis), and physician/pt preference (1 pt each). With a median follow-up of 8.3 months, the median time to progression is 4 months. Grade (G) 3/4 non-hematologic toxicity occurring in = 5%: infection (29%), nausea, vomiting (17% each), anorexia, hyperglycemia (13% each), and fatigue (8%). G3/4 hematologic toxicity: leukopenia (21%), neutropenia (41%), and thrombocytopenia (29%). Conclusions: In this preliminary analysis, S/P appears to have comparable activity to other platinum-based regimens. In an effort to reduce myelosuppression this trial has been amended to a S dose of 70 mg/m 2 . Additional accrual and follow-up are needed to better assess the safety and efficacy of this combination regimen. No significant financial relationships to disclose.