tbuckley/cabot-search huggingface dataset:
Bupropion improves sexual function in women diagnosed with breast cancer? A pilot study in this population
Authors: C. Mathias, E. Ponde de Sena, E. Demoraes, C. Bastos, M. I. Braghiroli, I. Rocha, G. Nunez, R. Athanazio, G. S. Lessa, A. Del Giglio
Journal: Journal of Clinical Oncology (2005)

8058 Background: Sexual morbidity after chemotherapy and hormonal therapy for breast cancer is an important problem that can negatively affect women’s quality of life. Bupropion is an antidepressant that appears to increase libido. Methods: We performed a pilot study using Bupropion in breast cancer patients that received adjuvant chemotherapy and were currently in use of hormonal therapy diagnosed with sexual dysfunction using the Arizona Sexual Experience Scale (ASEX), validated in Portuguese. This scale contains five questions that evaluate sexual function in the following areas: libido, excitability and hability to reach orgasm. The scale is coded, for each item as 1 (normal) to 6 (totally absent). Women received oral Bupropion 150mg/ daily for eight weeks and the ASEX, Beck’s Depression and the EORTC Q30 scales were applied prior to initiation of the study and on weeks 4 and 8. Results: Eight pacients were included in the study. The mean age was 49,75 +/- 3,95. Seventy five percent were married and 25% divorced. Fifty percent were caucasian and the other were afro descendents. Aproximately two thirds of the women were stage II and one third stage I. Seventy five percent underwent breast conserving surgery and 25% mastectomy. At the beginning of the study, mean ASEX score was 22.88 +/- 4.7. After four weeks of treatment we observed a reduction in the mean ASEX score that persisted until the end of the study: 17.50 (SD +/- 3.42, p = 0,014) and 17,88 (SD +/- 4.12, p = 0,001) respectively. Conclusion: This pilot study suggests that oral Bupropion 150mg/ daily is able to improve sexual function in women with breast cancer. We are currently expanding the study to further evaluate this benefit. No significant financial relationships to disclose.
A phase I study of a novel spectrum selective kinase inhibitor (SSKI), XL880, administered orally in patients (pts) with advanced solid tumors (STs)
Authors: J. P. Eder, L. Appleman, E. Heath, L. Malburg, A. Zhu, M. J. Pilat, G. Shapiro, P. Lorusso
Journal: Journal of Clinical Oncology (2006)

3041 Background: XL880 is a sub-nM inhibitor of the hepatocyte growth factor receptor (Met) and vascular endothelial growth factor (VEGF) family receptor tyrosine kinase (RTK). PDGFRβ, KIT, FLT3, and Tie-2 are also inhibited at low nM concentrations in vitro. XL880 is the 1 st orally bioavailable small molecule Met inhibitor to enter the clinic. Methods: Pts with advanced STs were enrolled in successive cohorts to receive XL880 orally as a single dose on Day (D) 1 with pharmacokinetic (PK) sampling, followed by 5 consecutive daily doses (DD) starting on D 4 with additional PK sampling. Pts then continued to receive XL880 for 5 consecutive days, repeated every 14 days. Results: Nineteen pts have been treated across 5 dose levels: 0.1, 0.2, 0.4, 0.8, and 1.6 mg/kg. No dose-limiting toxicities have been observed. Two pts have demonstrated grade 2 hypertension, at 0.8 and 1.6 mg/kg respectively. PK analysis indicated that systemic drug exposure (AUC) and peak plasma levels (Cmax) increased approximately dose-proportionally (r 2 values = .89 and .87 respectively) with increasing XL880 dose (0.1–1.6 mg/kg). Following 5 consecutive DD, AUC values were 175–304% higher and Cmax values were 30–203% higher than following a single XL880 dose, suggesting possible drug accumulation with repeat dosing. Terminal half-life values were ∼60 hours (hrs) following 5 consecutive DD (D 8 range: 40–66 hrs), were more variable following a single dose (D 1 range: 26–87 hrs), and appeared to be unaffected by dose. A pt with papillary renal cell carcinoma has a partial response (DD = 0.2 mg/kg) and pts with carcinoid and melanoma have had minor responses. Conclusions: XL880 is a RTK inhibitor with a novel spectrum of activity that targets both tumor cells and tumor-associated vasculature. XL880 is well tolerated up to the 1.6 mg/kg dose, with continued dose escalation ongoing. XL880 demonstrates biologic activity through hypertension and antitumor activity. [Table: see text]
Role of ALK activation in the development and maintenance of the neoplastic phenotype in neuroblastoma
Authors: M. Regairaz, F. Munier, H. Sartelet, V. Marty, M. Castaing, S. Michiels, M. Fabre, J. Roesel, G. Vassal
Journal: Journal of Clinical Oncology (2009)

10008 Background: Activating mutations of the Anaplastic Lymphoma Kinase (ALK) receptor could be responsible for most familial neuroblastoma cases and for up to 15% of somatic cases. The objective of the present study was to further investigate the role of ALK activation in neuroblastoma. Methods: Tissue microarrays were constructed containing 101 primary tumors and 56 paired normal tissues. Sections were immunostained with anti-ALK or anti-P-ALK antibodies, and with antibodies directed against the ALK ligands: PTN (Pleiotrophin) or MDK (Midkine). The Wilcoxon signed rank test was applied for comparison of paired data. Associations with prognostic factors were analyzed using t-tests. Effects of the ALK inhibitor TAE684 (Novartis) on cell proliferation and signaling was evaluated in wild-type or mutated ALK neuroblastoma cell lines and xenografts. Results: ALK was expressed in about 100% of tumors and normal tissues, while phospho-ALK was detected in 5% of normal tissues and 50% of tumors. Sequencing of the kinase domain of ALK showed that its phosphorylation was largely independent of mutations and we found that MDK and PTN ligands were expressed in 66% and 50% of tumors, respectively. Interestingly, ALK, P-ALK, and MDK were expressed at higher levels in tumors as compared with paired normal tissues (p &lt; 0.0001), while PTN showed an inverse tendency, being more expressed in normal tissues (p = 0.07). In tumors, P-ALK was associated with good-prognosis factors, including favorable stages (p = 0.01), absence of MYCN amplification (p = 0.05) and a younger age at diagnosis (p = 0.03). Inhibition of cell proliferation by TAE684 was detectible in all neuroblastoma cell lines, regardless of ALK status. However, TAE684 failed to demonstrate antitumor activity in advanced stage neuroblastoma xenografts expressing either a wild-type or a mutated ALK. Interestingly, ALK pathway activation (P-STAT3, P-AKT) was weak or barely detectible in these xenografts. Conclusions: ALK activation occurs during neuroblastoma oncogenesis, along with a concomitant switch between the expressions of PTN and MDK. However, ALK may not be a relevant therapeutic target since in vivo inhibition showed no antitumor activity. [Table: see text]
Long Term Follow-up of the GELF86 French and Belgian Trials: Complete Remission after First Line Treatment with Conventional Chemotherapy in Newly Diagnosed Follicular Lymphoma Patients Correlates with Prolonged Overall Survival Compared with Partial Remission
Authors: E. Bachy, P. Brice, M. Fournier, H. Tilly, C. Haioun, N. Brousse, S. Le Gouil, A. Bosly, B. Coiffier, C. Gisselbrecht, P. Solal-Celigny, G. Salles
Journal: Blood (2008)
Clinical significance of salvage surgery for recurrent pharyngeal or oral cancer after definitive radiation therapy.
Authors: K. Kagawa, H. Yamaguchi, H. Kizaki, N. Wakai, K. Aboshi, I. Sumida
Journal: Journal of Clinical Oncology (2010)

e16018 Background: In the treatment of pharyngeal or oral cancer, surgery causes so severe deterioration of phonation, swallowing function, and cosmesis that radiation therapy is usually preferred to surgery as a primary treatment. However, after curative doses of radiation therapy are administered, surgical procedures often become difficult because of tissue fibrosis and delay of healing, hence its clinical significance is controversial. This study investigated into clinical impacts of salvage surgery on overall survival (OS) of the patients with recurrent pharyngeal or oral cancer after definitive radiation therapy. Methods: Between January 1997 and December 2007, 126 patients with pharyngeal or oral squamous cell carcinoma were treated by radiation therapy with curative intents. Ninety-four patients (75%) had stage III or IV locally-advanced diseases. In 45 patients (36%), doxorubicin- or platinum-based systemic chemotherapy was administered concurrently with radiation therapy. The median radiation dose was 66Gy (range, 50-72). Within at least 2 years of follow-up, treatment failures were observed in 48 primary lesions, 27 regional lymph nodes, and 30 distant organs. Among 57 recurrent patients without apparent distant metastasis, salvage surgery was performed in 18 patients (32%). In 16 of the 18 patients (89%) the surgery covered primary lesions. In the other 2 patients only regional lymph nodes dissection was performed. Results: The median OS according to salvage treatment modality was 36 months by surgery, 25 months by chemotherapy, and 7 months by supportive care only (p<0.001). The median survival after salvage surgery was 25 months and survival over 1 year was obtained in 15 of 18 patients (83%). Nonetheless 2 patients died within 2 months after surgery because of aspiration pneumonia. The median survival after salvage chemotherapy was 8 months and no treatment-related death was observed within 6 months. Conclusions: In the treatment of recurrent pharyngeal or oral cancer, OS can be prolonged by salvage surgery, if possible, even after definitive radiation therapy. Meanwhile salvage surgery increases the risk of aspiration pneumonia which may be fatal and needs attention. No significant financial relationships to disclose.
Efficacy of everolimus in poor risk patients: Result of the POORTOR study.
Authors: Bernard J. Escudier, Sophie Abadie-Lacourtoisie, Ellen Blanc, Aline Guillot, Frank Priou, Hakim Mahammedi, Antoine Thiery-Vuillemin, Lionel Geoffrois, Nicole Tubiana-Mathieu, Antoine Adenis, Celine Ferlay, Laurence Albiges
Journal: Journal of Clinical Oncology (2015)

488 Background: Temsirolimus is currently the standard of care for poor risk RCC, based on the pivotal trial. Whether everolimus could be an alternative for such patients (pts) remain unknown. Methods: POORTOR is a prospective phase II study evaluating everolimus (10 mg daily) as first line therapy in RCC pts with at least 3 poor prognostic factors (IK &lt;80%, LDH &gt;1.5 NV, hemoglobin &lt;NV, corrected calcium &gt;NV, time from diagnosis to treatment &lt;1 year and more than one metastatic site. The primary endpoint was the 1-year overall survival (OS) rate. The sample size was calculated using a Simon’s two-stage Minimax design, with the following hypotheses: p 0 =40%, p1=54% (based on a 47% 1-year OS in the temsirolimus arm, NEJM 2007), an 8% one-sided alpha and a 90% power. Ninety-two (92) patients (pts) were needed with an interim analysis planned after 61 pts. Results: 62 pts have been enrolled in the first stage: median age 67, men 74%, clear cell 82.3%, nephrectomy 50%. 71% pts had IK &lt;80%, 77% pts had more than one metastatic sites, and 90% pts had a time from diagnosis to treatment &lt;1 year. All pts had at least 3 poor risk factors: 3 = 16.4 = 26. 5-6 = 20. Six pts had a partial response by investigator assessment. With a median follow up of 16.2 m, median PFS was 3.9 m (IC95%=[2.4;5.5]) and median OS was 6.0 m (IC95%=[4.2;8.6]). One-year OS rate was 29% (IC95%[19 \;42]) which resulted in premature stop of the study at the first step. SAE were reported in 22/62 pts (35.5%).Grade 3-4 AE related to everolimus were reported in 27/62 pts (43.5%). Dose reduction of everolimus was performed in 24 pts. Conclusions: This study confirms that poor risk patients still have a very short survival in RCC. Based on these results, everolimus is not a good option for this group of pts. However, our study population had a poorer prognosis compared to the temsirolimus arm of the Hudes et al. study, partly explaining the difference in OS between the 2 studies. Clinical trial information: NCT01888042.
Guilty feeling in smokers with lung cancer: A psychological study
Authors: S. Barni, M. L. Bonetti, M. Cabiddu, F. Petrelli, M. Cremonesi, A. Gamba, C. Moleri
Journal: Journal of Clinical Oncology (2008)

20642 Background: Scientific data confirms the correlation between smoking and cancer. Few articles describe the personal experiences of lung cancer patients (pts). Methods: In our department we compared the experiences of smokers (S) with non-smokers (NS) with lung cancer, their possible feeling of guilt and the strategies they use to face up to their illness. From November 2006 to December 2007, 57 pts in chemotherapy or in follow up were asked to undergo a specific psychological interview divided into four areas: awareness of disease, life-style (personal and family), feeling of guilt and coping strategies. Results: 42 pts were in the S group: 40 males (95.24%) and 2 females (4.76%); mean age 68.3 years old (range 65–69); 15 pts were in the NS group: 9 males (60%) and 6 females (40%); mean age 71 years old (range 65–74). 76.19% S and 73.33% NS were fully aware of having cancer. 50% S compared with 73.33% NS had other serious health problems prior to the diagnosis of cancer. There was a presence of familiarity for cancer in 18% NS against 65% S. 52.38% S were aware that smoking could cause lung cancer. Against 47.62% S believe that work, pollution and familiarity are possible causes of their lung cancer but not smoking. There is a predominant fatalistic coping style in the S group (42.85%), while the NS shows a prevalent reactive approach (60%). Conclusions: No feeling of guilt (78.57%) was noted in the S group regarding the cause of their disease. This could be due to their limited knowledge or ability of reasoning as a result of their low level of education (61.90% S pts had completed only primary school), due to a fatalistic coping style or due to a defence mechanism which the pt creates so as not to feel responsible for his disease and preserve a positive self image. No significant financial relationships to disclose.
BRAF gene contributes to melanoma pathogenesis but not to melanoma susceptibility
Authors: G. Palmieri, M. Casula, M. Colombino, M. P. Satta, C. Rozzo, P. A. Ascierto, G. Castello, G. Bianchi-Scarrà, A. Cossu, F. Tanda
Journal: Journal of Clinical Oncology (2004)

9584 Background: Somatic mutations of the BRAF gene has been recently reported in about two thirds of patients with malignant melanoma (MM). We here defined the contribution of BRAF to melanoma susceptibility, also making a comparison with the prevalence of CDKN2A germline mutations in MM patients from different geographical areas in Italy. Methods: Using a combination of DHPLC analysis and automated sequencing on genomic DNA from peripheral blood or tumor tissue samples, 569 melanoma patients (211 from North Italy and 358 from South Italy) were screened for BRAF mutations. Results: Three BRAF germline sequence variants (M116R, V599E, and G608H) were identified in 4/569 (0.7%) melanoma patients. High frequency (59%) of BRAF mutations was instead observed in tumor samples from cases also undergoing germline DNA analysis; at somatic level, substitution of valine 599 was found to account for majority (88%) of BRAF mutations. We then estimated the germline mutation rates in BRAF and CDKN2A among 358 consecutively-collected patients originating from South Italy; a low (2.5%) or very low (0.29%) prevalence of CDKN2A and BRAF mutations, respectively, was detected. Conclusions: Our study provides a clear assessment that mutational activation of the BRAF gene is a pathogenetic event contributing to melanoma tumorigenesis at somatic level with nearly absent participation to MM predisposition at germline level. Although at lower frequency in our population, germline CDKN2A mutations have been instead demonstrated to remain the major gene involved into the melanoma susceptibility. Work was supported by Associazione Italiana Ricerca sul Cancro and Regione Autonoma Sardegna. No significant financial relationships to disclose.
Change in pattern of relapse in newly diagnosed high-grade glioma following bevacizumab therapy.
Authors: M. L. Gruber, S. Kunnakkat, P. Medabalmi, D. B. Gruber, J. Golfinos, E. Parker, A. Narayana
Journal: Journal of Clinical Oncology (2010)

2020 Background: Local recurrence (LR) accounts for > 90% at the time of relapse in newly diagnosed high-grade glioma (HGG) following conventional therapy. Use of bevacizumab has shown impressive radiologic and clinical responses in both newly diagnosed and recurrent HGG. However, an apparent increase in diffuse invasive relapse (DIR) following therapy necessitated a detailed analysis of the pattern of recurrence. Methods: Seventy five patients with newly-diagnosed HGG were treated with radiation therapy and concomitant temozolomide (75 mg/m2 daily for 42 days) with bevacizumab (10 mg/kg every 2 weeks), 29 days following surgery, followed by 6 cycles of adjuvant TMZ (150 mg/m2 × 7d, q28 with bevacizumab at 10 mg/kg days 8 and 22 of each 28 day cycle. Recurrence was defined according to MacDonald Criteria. Pattern of recurrence and time to relapse were the primary aims of this study. DIR was defined as involvement of multiple lobes ± crossing the midline. Results: With a mean follow-up of 6.0 months (range 1-20), 40 patients have relapsed with 26 patients failing as DIR (65%). Seven patients who presented with multicentric HGG relapsed as DIR. The median progression-free survival (PFS) and overall survival (OS) were 8 (range 1-21 months) and 15 months (range 1-24 months) respectively for the entire group. The median OS for the patients who failed as DIR was 12 months vs. 4 months for patients with LR alone (p = 0.651). While the hazard risk for LR remained linear over time (R2 = 0.53), the risk of DR increased exponentially (R2 = 0.933). Biopsies done on five of these patients at the time of recurrence showed decreased expression of Olig-2 in 4 and increased expression of SDF-1 in 4 patients. No change in expression of HIF-1, p53, PDGF or CD163 was seen. Conclusions: Invasion remains a dominant process in newly diagnosed HGG treated with bevacizumab therapy. Unopposed angiogenic blockade resulting in increased invasiveness needs to be addressed in future clinical trials. No significant financial relationships to disclose.
Baseline Neutrophil to Lymphocyte Ratio Correlates with Tumor Stage in Locally Advanced Breast Cancer Patients
Authors: M. De Lisa, F. Ridolfi, M. Pistelli, A. Pagliacci, N. Battelli, Z. Ballatore, A. Santinelli, T. Biscotti, R. Berardi, S. Cascinu
Journal: Annals of Oncology (2014)
Phase II trial of gefitinib combined with docetaxel as first-line therapy in patients with metastatic breast cancer
Authors: F. Ciardiello, T. Troiani, F. Caputo, M. de Laurentiis, G. Tortora, G. Palmieri, F. de Vita, G. Colantuoni, S. de Placido, A. R. Bianco
Journal: Journal of Clinical Oncology (2005)

3080 Background: Epidermal growth factor receptor (EGFR) pathway activation is involved in breast cancer (BC) development and progression (Walker and Dearing, Breast Cancer Res Treat, 1999;53:167–173). Gefitinib (IRESSA), an EGFR tyrosine kinase inhibitor, has been shown to potentiate the antitumor activity of docetaxel in preclinical human BC models (Ciardiello et al, Clin Cancer Res 2000;6:2053–63). Methods: In a Phase II study, patients (pts) with metastatic BC received first-line combination therapy (CT) of oral gefitinib (250 mg/day) and intravenous docetaxel (75 [first 14 pts] or 100 mg/m2 [latter 27 pts] on Day 1 of a 3-week cycle). After 6 cycles maximum, pts received gefitinib monotherapy (MT) until progressive disease (PD) or unacceptable toxicity. Primary end point: antitumor activity (RECIST) after 3 and 6 cycles of CT and then every 6 weeks. Results: 41 pts were enrolled: median age, 58 years (range 40–75); previous adjuvant chemotherapy and/or hormonotherapy, 31 pts (75.6%); presence of metastatic visceral (lung and/or liver) sites, 34 pts (82.9%). There were no differences in efficacy or tolerability between the 2 docetaxel doses. For both dose groups, 38 pts (92.7%) were evaluable for response (≥1 cycle): 5 (13.2%) had complete response (CR), 17 (44.7%) had partial response (PR), 6 (15.8%) had stable disease (SD), 7 (18.4%) had PD, and 3 (7.9%) received only 1 cycle due to toxicity (grade [G] 3 diarrhea [n=1] and G2 acneiform rash [AFR, n=2]). Response rate (CR+PR) was 57.9% (95% confidence interval [CI] 45, 80) and disease control rate (CR+PR+SD) was 73.7% (95% CI 68, 95). After 6 cycles, 22 responders (CR+PR) continued to receive gefitinib MT (median duration of MT: 21 weeks [range 2–82+]) and 2 pts with PR on CT achieved CR; pts with SD received second-line chemotherapy. The most frequent G2 adverse events (AEs) included diarrhea (14.6%) and AFR (7.3%). G3/4 AEs were neutropenia (51.2%), diarrhea (12.2%), AFR (4.9%), febrile neutropenia (2.4%), and anemia (2.4%). Conclusions: Gefitinib and docetaxel show encouraging antitumor activity as first-line CT in metastatic BC and are well tolerated. Further clinical evaluation is warranted. IRESSA is a trademark of the AstraZeneca group of companies Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration AstraZeneca
Vitamin K antagonism aggravates chronic kidney disease–induced neointimal hyperplasia and calcification in arterialized veins: role of vitamin K treatment?
Authors: Emma Zaragatski, Jochen Grommes, Leon J. Schurgers, Stephan Langer, Lieven Kennes, Miriam Tamm, Thomas A. Koeppel, Jennifer Kranz, Tina Hackhofer, Karen Arakelyan, Michael J. Jacobs, Maria Kokozidou
Journal: Kidney International (2015)

Arteriovenous fistula (AVF) is the common vascular access type for a hemodialysis patient. Its failure is due to neointimal hyperplasia. Vitamin K antagonists are given to lower thrombosis tendency, but have side effects that enhance arterial calcifications. Here, we investigated the effects of vitamin K antagonists and vitamin K2 (K2) treatment on neointimal hyperplasia development and calcification in rats and in arterialized human veins. AVF was generated in female rats while chronic kidney disease (CKD) was induced using an adenine-enriched diet. Arterialization, CKD, and vitamin K antagonists all significantly enhanced venous neointimal hyperplasia. K2 treatment, additional to vitamin K antagonists, significantly reduced neointimal hyperplasia in arterialized veins in healthy rats but not in rats with CKD. Arterialization, CKD, and vitamin K antagonism all significantly increased, whereas K2 supplementation attenuated calcification in healthy rats and rats with CKD. K2 significantly enhanced matrix Gla protein carboxylation in control rats and rats with CKD. Arterialized human vein samples contained inactive matrix Gla protein at calcification and neointimal hyperplasia sites, indicating local vitamin K deficiency. Thus, vitamin K antagonists have detrimental effects on AVF remodeling, whereas K2 reduced neointimal hyperplasia and calcification indicating vasoprotective effects. Hence, K2 administration may be useful to prevent neointimal hyperplasia and calcification in arterialized veins
Activated Dendritic Cells From Bone Marrow Cells of Mice Receiving Cytokine-Expressing Tumor Cells Are Associated With the Enhanced Survival of Mice Bearing Syngeneic Tumors
Authors: Shin-ichiro Fujii, Hirofumi Hamada, Koji Fujimoto, Taizo Shimomura, Makoto Kawakita
Journal: Blood (1999)