tbuckley/cabot-search huggingface dataset:
A phase I/II study of cetuximab in combination with 5-fluorouracil (5-FU)/folinic acid (FA) plus weekly oxaliplatin (L-OHP) (FUFOX) in the first-line treatment of patients with metastatic colorectal cancer (mCRC) expressing epidermal growth factor receptor (EGFR). Preliminary results
Authors: T. Seufferlein, C. Dittrich, J. Riemann, E. Woell, T. Herrmann, F. Lordick, D. Arnold, K. Olchowka, T. Hoehler, H. J. Schmoll
Journal: Journal of Clinical Oncology (2005)

3644 Background: Cetuximab (Erbitux) is an EGFR-targeting IgG1 monoclonal antibody that showed in combination with 5-FU/FA/L-OHP (FOLFOX4) one of the highest response rates ever reported in 1st-line treatment of mCRC. Methods: This phase I/II trial of standard dose cetuximab in combination with L-OHP and infusional 5-FU/FA in a weekly schedule (AIO FUFOX protocol) was conducted in order to investigate the recommended dose and the efficacy of this combination at the respective dose level. In the phase I part cetuximab and L-OHP/FA were given at their fixed doses while two dose levels of 5-FU were investigated (cetuximab 400 mg/m2 i.v. in week 1 followed by 250 mg/m2 i.v. weekly; L-OHP 50 mg/m2; FA 500 mg/m2, 5-FU 1,500 mg/m2 [dose level 1] or 2,000 mg/m2 [dose level 2] i.v. over 24h weekly for 4 weeks followed by 1 week rest). Results: 49 pts have been enrolled, M/F 31/18, median age 62 years (39 - 78), median ECOG performance status 0 (0 - 2). 48 pts are assessable for safety and efficacy. In the phase I part dose limiting toxicities consisting of diarrhea gr 3 occurred in 1 (14%) out of 7 pts and in 3 (20%) out of 15 pts treated at dose level 1 (DL1) and 2 respectively. Consequently, DL2 using cetuximab together with L-OHP/5-FU/FA at their standard doses was considered as recommended dose (RD) for phase II and was expanded to 41 pts. Common gr 3/4 toxicities (pts ≥ 5%, multiple cycles at the RD): neutropenia 10%, mucositis 7%, gr 3 toxicity: diarrhea 24%, neurological 10%, skin 17%. Efficacy: 54% (95% CI 38 - 69%) confirmed remission including one CR was achieved in 41 pts at the RD and 5 (71%, 95% CI 29 - 96%) out of 7 pts at DL1 showed a PR. 3 PR pts at the RD underwent surgery for metastases. Median progression free survival time will be presented. Conclusion: The combination of cetuximab and FUFOX showed at the RD an acceptable safety profile and promising efficacy. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Merck KGaA Merck KgaA, sanofi-aventis Merck KgaA, sanofi-aventis Merck KgaA, sanofi-aventis
Photodynamic therapy using Laserphyrin for centrally located early stage lung cancer
Authors: J. Usuda, H. Kato, T. Okunaka, K. Furukawa, H. Honda, Y. Suga, T. Hirata, T. Ohira, M. Tsuboi, T. Hirano
Journal: Journal of Clinical Oncology (2006)

7229 Background: In central type early stage lung cancer, the tumor must be located only as far as the segmental bronchi and be carcinoma in situ or with only limited invasion into the bronchial wall. Laserphyrin (mono-L-aspartyl chlorine e6, NPe6) is a second generation photosensitize and approved by the Japanese government and has been on sale from June 2004. Methods: Four h after the administration of Laserphyrin 40 mg/m 2 , we irradiated using diode laser (100 mJ/cm 2 ). Before PDT, we evaluated the tumor lesions and tumor depth using autofluorescence bronchoscopy and endobronchial ultrasonography (EBUS), and we confirmed the area of laser irradiation. Results: From February 1980 to December 2005, a total number of 204 patients with 264 lesions of centrally located early stage lung cancer underwent photodynamic therapy (PDT) in the Department of Thoracic Surgery, Tokyo Medical University Hospital. There were 185 clinical stage 0 lesions and 79 stage I lesions. CRs and PRs were obtained in 224 lesions (84.8%) and 40 lesions (15.2%) out of 264 lesions. From July 2004 to December 2005, we performed Laserphyrin-PDT for 28 lesions of centrally located early stage lung cancer in Tokyo Medical University Hospital. The rate of CR was 92.9% (26 lesions) in 28 lesions. For Laserphyrin-PDT, Skin photosensitivity was very low and the clean-up bronchoscopies were not frequently needed, and the period of hospitalization was shorter compared to that for Photofrin-PDT. Conclusions: We conclude that PDT using Laserphyrin will be a standard option for stage 0 (TisN0M0) and stage I (T1N0M0) centrally located early stage lung cancer. No significant financial relationships to disclose.
Temsirolimus for advanced renal cell carcinoma (RCC): Compassionate versus commercial use
Authors: P. R. Bojanapally, S. Graham, A. L. Rustine, L. A. Sacris, J. P. Dutcher
Journal: Journal of Clinical Oncology (2008)

16139 Background: Temsirolimus, a specific inhibitor of the mammalian target of rapamycin kinase, has been approved on May 31st, 2007 for treatment of metastatic renal carcinoma based on a study which showed improved survival compared to interferon among patients with metastatic renal cell carcinoma and poor risk features. Methods: In this single institution study, we have treated 15 patients (8 patients on compassionate use and 7 patients on commercial use). All patients had prior nephrectomy and received prior systemic immunotherapy and (or) chemotherapeutic agents (sutent, sorafenib, avastin, gemzar, HDIL2, interferon, AG 013736, Adriamycin). 93% of the patients had at least 3 of the 6 predictors of poor prognosis for RCC. Temsirolimus was administered as 25 mg I.V infusion weekly. The primary end point was overall survival. Results: Patients in commercial group of temsirolimus use had a better performance status and had received less number of prior systemic treatments and received more doses of temsirolimus and had a median survival of 4+ months still continuing (range 2 to 6+ months) compared to compassionate group with a median survival of 2.5 months (range 30 days to 8 months). 1 patient from each group had to discontinue the study due to the rapid progression of the disease. 1 patient from each group had stable disease for 18+ weeks still continuing. No lethal toxicities observed in these patients. Conclusion: Patients who received less number of prior systemic treatments received more doses of temsirolimus and had a prolonged survival. Baseline patient characteristics Patient Characteristics (M- Median, R- Range) Compassionate group (8) Commercial group (7) M/F 5/3 3/4 Age M 60 56 R 39-78 39-81 Time from Dx to Rx M 5 yrs 4 yrs R 3-24 yrs 2-16 yrs # Prior Rx # Cycles M 20 15 R 3–23 1-29 # Agents M 4 2 R 1-9 1-7 Performance status M 3 2 R 1-4 1-3 Median survival M 2.5 months 4+ months R 1-8 months 2-6+ months Time from last Rx to temsirolimus M 75 days 15 days R 15 days-2 yrs 10 days-1.5 yrs No. of temsirolimus doses M 7 8+ R 2-25 5-15+ Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration Bayer, Genentech™ BioOncology, Novartis, Onyx, Pfizer Oncology, Wyeth Bayer, Novartis, Onyx, Pfizer Oncology, Wyeth Bayer, Genentech™ BioOncology, Novartis, Onyx, Pfizer Oncology, Wyeth
Neck dissection following organ preservation protocols prolongs feeding tube dependence in patients with advanced head and neck cancer
Authors: M. Lango, K. Ende, S. Ahmad, S. J. Feigenberg, J. A. Ridge
Journal: Journal of Clinical Oncology (2006)

5525 Background: Organ preserving strategies employed in the treatment of advanced stage head and neck cancer frequently result in significant organ dysfunction including dysphagia and feeding tube dependence. While the acute and chronic effects of radiation and chemotherapy are known to contribute to swallowing impairment, the effect of a neck dissection, performed 6–8 weeks following the completion of treatment is unknown. Methods: Retrospective review of Stage III/IV squamous carcinoma patients treated with primary radiation with/without chemotherapy and a post-treatment neck dissection, who remain free of locoregional or distant failure for a minimum of two years. Predictors of prolonged feeding tube dependence (&gt;24 months following the completion of treatment) were evaluated using univariate and multivariate analysis. To determine the independent effect of neck dissection on length of feeding tube dependence, patients matched for covariates were also compared. Results: 79 patients treated at the Fox Chase Cancer Center between 1992 to 2003 were included in this study. 61 (77.2%) received chemotherapy and 37 (46.8%) underwent a neck dissection. The surgical specimen was positive for residual carcinoma in 12 patients (33%). 57 patients (71.3%) underwent placement of a feeding tube. The median time to removal of feeding tubes was 12 months [7–17 months, 95% CI]. Feeding tube-free status at 24 months was associated with use of standard radiotherapy (p = 0.031), N0 vs N+ neck stage (p = 0.041) and management without a neck dissection (p = 0.003). There was no association with age, T-stage, tumor site or use of chemotherapy. On multiple regression, only neck dissection remained a predictor of retained feeding tube at 24 months (p = 0.013). In patients matched for N-stage and treatment selection, those who underwent a neck dissections required a feeding tube a median of 36 months compared with 10 months for those without a neck dissection [32–57 months versus 7–13 months, 95% CI, p = 0.021]. The two year frequency of feeding tube dependence was 14/34 (41%) versus 3/30 (10%), respectively (p = 0.005). Conclusions: Neck dissection may contribute dysphagia experienced by head and neck cancer patients treated with organ preservation protocols. No significant financial relationships to disclose.
Phase I trial of NPI-2358 (a novel vascular disrupting agent) plus docetaxel
Authors: M. Millward, A. Mita, M. A. Spear, K. C. Federico, G. K. Lloyd, G. Cropp, M. Mita, P. Mainwaring
Journal: Journal of Clinical Oncology (2009)

3571 Background: NPI-2358 is a vascular disrupting agent (VDA) that destabilizes tumor vascular endothelial cell architecture resulting in selective collapse of established tumor vasculature. In murine tumor models NPI-2358 produces tumor regression alone and synergistically with agents such as paclitaxel, docetaxel (TXT) and irinotecan, often with decreased toxicity. Methods: The objective was to determine the Recommended Phase 2 Dose (RP2D) of NPI-2358 in combination with TXT. Patients with previously treated advanced NSCLC or other malignancies where TXT use was appropriate were enrolled. Patients received 75 mg/m 2 TXT every 21 days. NPI-2358 was administered IV 2 hours after TXT on Day 1, and alone on Day 8. The dose of NPI-2358 was escalated from the single agent biologic effect dose (BED) of 13.5 mg/m 2 to the single agent RP2D of 30 mg/m 2 using a 3+3 design. PK was assessed on Days 1 and 8. Results: 13 patients were enrolled of whom 10 had NSCLC. At all dose levels adverse events were consistent with those of both agents given alone. Adverse events commonly associated with NPI-2358 were seen, including nausea, vomiting, fatigue, fever, tumor pain and transient blood pressure elevations. One DLT of nausea, vomiting, dehydration and neutropenia occurred at 30mg/m 2 . PK analysis did not indicate a drug-drug interaction. Of the patients with NSCLC, 8 had measureable disease of which 2 demonstrated a partial response (PR), with 4 others having lesser regressions. The RP2D was thus 30 mg/m 2 of NPI-2358 with 75 mg/m 2 TXT. Conclusions: The combination of full dose NPI-2358 and TXT is tolerable. Although a limited data set, activity appears favorable relative to the 5–10% response rate reported with TXT alone in this population. Based on these results, efficacy is now being assessed in Phase 2 (the ADVANCE study), a randomized comparison of TXT ± 30 mg/m 2 of NPI-2358 in 2 nd - line NSCLC. Of note, entry criteria allow patients with squamous cell carcinoma, as VDAs do not appear to result in unfavorable outcomes associated with some other agents in this sub-population. [Table: see text]
registHER: Treatment outcomes in patients with HER2-positive (HER2+), hormone receptor-positive (HR+) metastatic breast cancer (MBC)
Authors: D. Tripathy, P. Kaufman, A. Brufsky, M. Mayer, M. Yood, L. Wang, M. Brammer, D. Yardley, E. Tan-Chiu, H. Rugo
Journal: Journal of Clinical Oncology (2009)

1057 Background: Approximately 50% of HER2+ breast cancers are HR+ (defined as estrogen receptor [ER] and/or progesterone receptor [PR] positive). Cross talk between growth factor and ER-dependent signaling pathways may affect growth regulation in HER2+ breast cancers. Blockade of both pathways appears to be more active than blocking either alone based on randomized trials performed in selected populations. However, the outcomes of HER2+ and HR+ MBC patients relative to those in real- life clinical practice have not been evaluated in large cohort studies. Methods: registHER is a prospective observational study of 1023 patients with newly diagnosed (within 6 months [mo]) HER2+ MBC treated in community/academic settings, enrolled from 12/03 to 2/06. Median follow-up from MBC diagnosis was 25 mo at data cutoff (1/02/08). Treatment patterns and outcomes in patients with HER2+/HR+ MBC receiving 1st-line therapy (i.e., therapies received prior to 1st progression) are described in this analysis. Results: Of the 963 (94%) treated HER2+ patients with recorded HR tumor status, 55% (533) were HR+ and 45% (430) were HR-negative. 1st-line MBC treatment regimens for HER2+/HR+ patients included endocrine therapy (E) only, 57 (10.7%); E + trastuzumab (T), 50 (9.4%); chemotherapy (C) ± E, 41 (7.7%); and C + trastuzumab (T) ± E, 361 (67.7%). Progression-free survival (PFS) and overall survival (OS) by 1st line treatment groups are in the table. Conclusions: In registHER, HER2+/HR+ patients treated with E+T had longer PFS than patients treated with E alone; E- alone median PFS is consistent with findings in prospective randomized trials. These data provide further information regarding trastuzumab's role in targeting dual pathways in HER2+/HR+ MBC patients in a real-world setting. Multivariate analysis to address potential bias from known prognostic factors that may influence treatment choice will be presented. [Table: see text] [Table: see text]
Efficacy against asthma demonstrated for a house dust mite allergen immunotherapy tablet
Authors: H. Mosbech, F. de Blay, R. Deckelmann, J. Korsgaard, Inga Malcus, E. Pastorello, L. Andres, E. Trebas-Pietras, B. Andersen, G. Canonica
Journal: Allergy (2009)
The influence of sex on efficacy, toxicity and delivery of treatment in National Cancer Institute of Canada Clinical Trials Group (NCIC CTG) non-small cell lung cancer (NSCLC) chemotherapy trials
Authors: P. Wheatley-Price, A. Le Maître, K. Ding, N. B. Leighl, V. Hirsh, L. Seymour, F. A. Shepherd
Journal: Journal of Clinical Oncology (2008)

8054 Background: Outcomes in lung cancer may differ by sex, with some studies reporting longer survival in women. Increased chemotherapy (CT) toxicity has been reported in women with small cell lung-cancer. We investigated the influence of sex on efficacy, toxicity, quality of life (QoL) and dose-delivery in NSCLC. Methods: This is a pooled analysis of three NCIC CTG phase III clinical trials: BR.10 (Stage I/II: adjuvant vinorelbine/cisplatin vs. observation), BR.14 (Stage IIIB/IV: vinorelbine/gemcitabine vs. gemcitabine/cisplatin or vinorelbine/cisplatin) and BR.18 (Stage IIIB/IV: carboplatin/paclitaxel plus BMS 275291 or placebo). Endpoints included overall survival (OS), progression free survival (PFS), response rate (BR.14 and BR.18 only), QoL, dose intensity (DI) and toxicity. Results: Of 1090 patients who received chemotherapy, 320 (29%) were women. At entry, women were more likely to have adenocarcinoma (70% vs. 44%, p<0.0001), be normal or underweight (60% vs. 49%, p<0.0001), and less likely to have anemia (29% vs. 55%, p<0.0001), diabetes or chronic lung disease compared to men. There were no significant differences in chemotherapy DI other than higher gemcitabine DI in women in BR.14, although there were trends for lower DI in women in BR.10, and more treatment delays and carboplatin omissions in BR.18. Women were less likely to have mild anemia and renal toxicity on treatment, but more likely to have mild nausea and vomiting. There were no differences in grade 3 or 4 toxicities. Response rates were similar in both sexes in BR.14 and BR.18 (27.4% vs. 31.2%, p = 0.27). Women had longer OS (HR 0.79 [0.67–0.93], p=0.007) and PFS (HR 0.79 [95% CI 0.68–0.92] p=0.002). In multivariate analyses, female sex remained a significant predictor of prolonged PFS, while anemia and non- squamous/adenocarcinoma pathology predicted shortened PFS; only anemia was predictive of shortened OS. There was no difference in global QoL changes. Conclusions: Women in these studies have a modest PFS benefit from CT for NSCLC, but no major differences in OS, response rate, DI, severe toxicity or QoL. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration OSI Oncology, Roche Lilly Oncology, OSI Oncology, Roche Roche
Chemotherapy in the treatment of NSCLC and brain metastases
Authors: J. Baekke, H. Sindrup, R. Olesen, T. Palshof, C. Rytter, O. Hansen
Journal: Journal of Clinical Oncology (2004)

7116 Background: 611 chemonaive patients with advanced NSCLC from three oncologic centers were treated with Carboplatin (AUC=5) and Vinorelbine (30 mg/m2 d.1+8) q3w as a standard regimen outside protocol from March 1998 to January 2003. 47 patients had brain metastases at the time of chemotherapy Methods: Data were retrospectively collected from patient files. The outcome of patients with and without brain metastases were compared Results: Among patients with brain metastases median age was 58 years (range 38–70 years). 25 (53%) were men and 22 (47%) women. Metastatic pattern of the patients with brain metastases: Liver 11%. Bone 6%. Adrenal glands 13%. Lung metastases 17%. Cutan 2%. None of the patients had lymphnodes outside mediastinum or pleural effusion. 85% had WHO PS=0–1, 11% PS=2, 4% not stated. No patients were lost to follow up. Six of the patients with brain metastases had recurrent disease of lung cancer. 25 of the patients with brain metastases had the brain only as metastatic site. 2 patients received stereotactic irradiation for a solitary brain metastasis before chemotherapy. 34/47 of patients were treated with palliative total brain irradiation of 20–30 Gy/ 4–10 fractions before chemotherapy and 11 patients during or after chemotherapy. One patient did not receive irradiation of the brain. Overall survival of the patients with brain metastasis was 8.0 months. This was identical to patients without brain involvement. Overall median survival of the 564 (92%) patients without brain metastases was 8.0 months (p=0.91). 1-year and 2-year survival rate were 31% and 11% respectively in this population. There was no significant differences in performance status in the two groups, but the patients in the brain metastatic group had a lower median age (58 vs 62 years, p<0.001) . Age, sex, performance status, histology, low hemoglobine, metastases to brain, liver, bone, lymphnodes outside mediastinum and lung were included in multivariate analysis in 611 patients. Brain-, lung and bone metastasis, histology and age were not related to poorer survival Conclusions: Patients with NSCLC and brain metastases in good condition do as well as patients without brain metastases when treated with pallitive chemotherapy Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Pierre Fabre
Suicidality and HIV status
Authors: F P McKegney, M A O'Dowd
Journal: American Journal of Psychiatry (1992)

Among psychiatric consultation patients, 322 AIDS patients were significantly less suicidal than 82 other HIV-positive patients and were comparable in suicidality to 1,086 patients with negative or unknown HIV status. AIDS patients had significantly more organic mental disorders. Organicity, denial, acceptance, and/or preoccupation with a fatal illness may reduce suicidality in AIDS patients.
Ratiometric and Allometric Relations Between Left Atrial Dimension and Measures of Body Size: the EchoNoRMAL Collaboration
Authors: Giovanni de Simone, Ernst R. Rietzschel, Iana Simova, Liza Thomas, Raffaele Izzo, Havard Dalen, F. D. Richard Hobbs, Arnold C. Ng, Christopher M. Triggs, Katrina K. Poppe, Gillian A. Whalley
Journal: Circulation (2013)
Abstract A07: Loss of Rpl22 promotes tumor progression through regulation of angiogenesis and dissemination.
Authors: Shuyun Rao, Jason E. Stadanlick, Kathy Q. Cai, Wiest L. David
Journal: Clinical Cancer Research (2015)

Abstract Mutations in ribosomal proteins (RP) often cause bone marrow syndromes associated with increased risk for cancer development. We have shown that Rpl22 is a haploinsufficient tumor suppressor in T acute lymphoblastic leukemia (T-ALL). Indeed, loss of one Rpl22 allele accelerates T-cell lymphomagenesis in the murine Akt transgenic mouse model, by inducing the stem cell factor Lin28B in an NFκB-dependent manner. Moreover, mice lacking both Rpl22 alleles exhibited significantly increased thymic tumor size, which was associated with poor survival and markedly enhanced angiogenesis relative to Rpl22 heterozygous mice or wild type. The increased angiogenesis in the mediastinal mass was linked to upregulation of VEGFA and downregulation of S1P1. Loss of S1P1 is sufficient to block egress of lymphoma cells from thymus. Rpl22-deficient thymic lymphoma lines also exhibit enhanced growth upon adaptation to growth in vitro, and this is reversed by ectopic expression of Rpl22. Rpl22 expression also represses the expression of proteins that promote traversal of the cell cycle. Collectively, the increased tumor growth and angiogenesis, and the blockade of thymic egress contribute to the enlarged mediastinal masses observed in Rpl22-deficient mice. Rpl22-mutant T-ALL are a molecularly distinct subtype exhibiting increased aggression and treatment resistance. Accordingly, our identification of a number of signaling pathways controlled by Rpl22 may enable the development of novel strategies, such as targeting angiogenesis, in such cases of T-ALL. Citation Format: Shuyun Rao, Jason E. Stadanlick, Kathy Q. Cai, Wiest L. David. Loss of Rpl22 promotes tumor progression through regulation of angiogenesis and dissemination. [abstract]. In: Proceedings of the AACR Special Conference on Hematologic Malignancies: Translating Discoveries to Novel Therapies; Sep 20-23, 2014; Philadelphia, PA. Philadelphia (PA): AACR; Clin Cancer Res 2015;21(17 Suppl):Abstract nr A07.