tbuckley/cabot-search huggingface dataset:
Cetuximab plus FOLFIRI first line in patients (pts) with metastatic colorectal cancer (mCRC): A quality-of-life (QoL) analysis of the CRYSTAL trial
Authors: G. Folprecht, M. Nowacki, I. Lang, S. Cascinu, I. Shchepotin, J. Maurel, P. Rougier, D. Cunningham, A. Zubel, E. Van Cutsem
Journal: Journal of Clinical Oncology (2009)

4076 Background: Assessing QoL is important to evaluate the impact of treatment on pts with mCRC. The phase III CRYSTAL trial compared cetuximab plus FOLFIRI with FOLFIRI alone in the first-line treatment of patients with EGFR-expressing mCRC. Primary endpoint was progression-free survival (PFS); QoL was a secondary endpoint. Methods: Pts were randomised 1:1 to cetuximab (400 mg/m 2 initial dose then 250 mg/m 2 /wk) plus FOLFIRI q2w (irinotecan 180 mg/m 2 , folinic acid 400 mg/m 2 , 5-FU bolus 400 mg/m 2 , 5-FU infusion 2400 mg/m 2 over 46 h) (Group A, n=599) or FOLFIRI alone (Group B, n=599). QoL was assessed with the EORTC QLQ-C30 (v3.0) questionnaire. Pts were to complete the questionnaire at baseline, every 4 cycles, and at final tumor assessment. The primary QoL analysis focused on Global Health Status and Social Functioning scales and employed a pattern-mixture model that included the drop-out pattern. Descriptive statistics were provided for each multi-item scale considering QoL changes over time. Results: Risk of disease progression was significantly reduced by 15% (HR=0.85) in favor of Group A (p=0.0479); pts with KRAS wild-type (wt) tumors in Group A had a 32% (HR=0.68) reduced risk of progressing. Questionnaire completion compliance rates were similar between treatment groups. Pattern-mixture analyses showed no statistically significant differences between the two treatment groups for changes from baseline on the Global Health Status (p=0.29) and Social Functioning (p=0.39) scales. Comparing treatment groups in terms of QoL scores over time resulted in no statistically significant differences, apart from nausea/vomiting in favor of the cetuximab group at week 16 (10.2 vs 13.3; p=0.0129), week 32 (9.3 vs 12.5; p=0.0488) and week 40 (7.6 vs 12.5; p=0.0194). Conclusions: In pts with mCRC, cetuximab plus FOLFIRI first-line significantly prolongs PFS compared with FOLFIRI alone while preserving QoL. The PFS benefit is even more pronounced for pts with KRAS wt tumors. The EORTC QLQ-C30 Social Functioning scale was expected to reflect skin reactions related to cetuximab, but there was neither a clinically meaningful nor statistically significant difference between groups. [Table: see text]
Prognostic impact of body mass index upon cancer recurrence and survival in stage III colon cancer patients from adjuvant chemotherapy trials
Authors: F. Sinicrope, N. R. Foster, D. J. Sargent, S. R. Alberts, M. J. O'Connell
Journal: Journal of Clinical Oncology (2009)

11088 Background: Obesity is associated with an increased risk of colon cancer. However, the influence of body mass index (BMI) upon the prognosis of patients with established colon cancer remains unknown. Methods: We conducted a retrospective study of 1,803 patients with surgically resected stage III colon cancer who were enrolled in five randomized trials of 5-fluorouracil-based adjuvant chemotherapy conducted by the North Central Cancer Treatment Group. Patient height and weight were recorded at study entry and BMI (kg/m 2 ) was calculated and categorized. Cancer recurrence or death were monitored during 5 years of follow-up. The score and likelihood ratio p-values were determined from univariate and multivariate Cox regression models respectively, after stratifying by study. Results: Among stage III colon cancer patients, 19% were obese (BMI 30 kg/m 2 ), 37% were overweight (BMI, 25 to 29.9 kg/m 2 ), 38% were of normal-weight (BMI, 20 to 24.9 kg/m 2 ), and 6% were underweight (BMI &lt; 20 kg/m 2 ). Obese versus normal-weight patients showed higher rates of lymph node (LN) metastasis (&gt;3 LNs; 38% vs. 29%, p &lt;0.01) and tumor site was more likely to be distal versus proximal (52% vs. 45%, p= 0.03). No differences in age, gender, or histologic grade were found. In a univariate analysis, obese patients had significantly worse disease-free survival (DFS) compared with normal-weight patients (hazard ratio 1.25 (95% CI: 1.04 -1.51; p= 0.02). The 5 year DFS rates were 49% in obese patients versus 57% in normal weight subjects. Furthermore, poorer DFS was observed for obese patients after adjusting for age, sex, histologic grade, and tumor site (p= 0.03). Neither overweight nor underweight patients (vs. normal-weight) had significantly different DFS. Analysis of the predictive impact of BMI for 5-FU-based adjuvant therapy is in progress. Conclusions: Obesity (BMI 30 kg/m 2 ) was associated with a greater number of metastatic lymph nodes and poorer disease-free survival in patients with stage III colon cancer, suggesting that obesity influences tumor progression. No significant financial relationships to disclose.
A novel way of assessing health and vulnerability in older newly diagnosed cancer patients: An ongoing prospective pilot study
Authors: M. Puts, J. Monette, V. Girre, C. Pepe, M. Monette, L. Panasci, M. Basik, G. Batist, C. Wolfson, H. Bergman
Journal: Journal of Clinical Oncology (2008)

20707 Background: Oncologists may have difficulty in determining appropriate treatment and predicting complications in older patients. In this regard, the concept of frailty may be a useful way to characterize their health, functional status and vulnerability. Methods: Objectives: 1) To evaluate the recruitment and retention strategy and the feasibility of the selected measurement tools. 2) To describe the health and vulnerability of older cancer patients and the adverse outcomes of treatment. In this pilot prospective cohort study, baseline interviews are conducted before the start of cancer treatment. Second and third face-to-face interviews are conducted at 3 and 6 months in which oncology data and data on treatment toxicity are abstracted from the medical chart. Telephone interviews are conducted at 1.5 and 4.5 months. Study Population: Cancer patients aged 65 and older referred to the Segal Cancer Center with a new diagnosis of breast, colorectal or lung cancer, lymphoma or myeloma, able to give informed consent, life expectancy>3 months, who have not received cancer treatment in the previous five years. Data collected: Sociodemographics, health (comorbidity, medication use and self-rated health), cancer related information (e.g. type of cancer, stage and treatment regime), functional status (ECOG, ADL, IADL, functional limitations), frailty markers (nutrition, cognition, mood, mobility, strength, energy, physical activity) and quality of life. The primary outcome measures are changes in vulnerability/frailty and treatment toxicity. The secondary outcome measure is use of health care services. Results: 93 patients are included: mean age 73.3, 27 men and 66 women (response 72%). Diagnoses: breast 35, lung 27, colorectal 13, lymphoma 14, multiple myeloma 4. Proposed treatment plan: surgery 42, chemotherapy 30, combination radio/chemotherapy 6, radiotherapy 7, hormonal therapy 2, watchful waiting 5. The majority (86%) had ≥ 1 frailty marker at baseline, 33 (35%) had IADL disability and 8 (9%) had ADL disability. Conclusions: This pilot study will contribute to the best design for a longitudinal prospective study on health and functional status in older newly diagnosed patients. No significant financial relationships to disclose.
A phase I/II trial of the oral PKC-inhibitor PKC412 (PKC) in combination with imatinib mesylate (IM) in patients (pts) with gastrointestinal stromal tumor (GIST) refractory to IM
Authors: P. Reichardt, D. Pink, T. Lindner, M. C. Heinrich, P. S. Cohen, Y. Wang, R. Yu, A. Tsyrlova, S. Dimitrijevic, C. Blanke
Journal: Journal of Clinical Oncology (2005)

3016 Background: Some GIST patients with response to IM develop resistance to IM. A favorable kinase inhibition profile of PKC (KIT, PDGFR-1,-2, VEGFR-2) and synergistic IM in vitro data provided the rationale for this non-randomized, open label study. Methods: Pts with metastatic GIST were eligible if they progressed after ≥4 months on IM therapy, including at least 2 months at ≥600mg/d. Drug administration and PK schedules were designed to assess the safety and tolerability of the combination, as well as the PK interaction between IM and PKC. Results: Nineteen patients have been entered so far at doses ranging from IM 600 to 1000mg/d in combination with PKC 200mg/d. Frequently reported CTC Gr 1–2 adverse events in this heavily pretreated group of patients included nausea, vomiting, anorexia, diarrhea, edema, fatigue, dyspepsia, candidiasis, sweating, skin toxicity and anemia. Four Grade 3 AEs were attributed to the investigational combination: hyperglycemia, transient asymptomatic hyperamylasemia, hypercalcemia and transaminitis, all reported previously for PKC alone. Notably, hyperthyroidism manifested by elevated TSH (grade 2, manageable) was seen in 4/12 patients. Complete PK data for the first twelve patients treated with PKC 100 mg b.i.d. in combination with IM 600mg q.d. from 2 to 5 months show that PKC trough plasma concentrations increased ∼2-fold over that seen in AML studies with PKC alone, even taking into account the expected decrease in the PKC plasma concentration of ∼75% by day 28 seen in previous AML studies with PKC. IM exposure decreased ∼70% after one month of co-administration with PKC, either due to enzyme induction or protein binding interactions. The study was therefore amended to allow for inter-cohort dose escalation of IM and temporary dose reduction of PKC to decrease peak levels which resulted in reduced toxicity and increased IM PK trough levels equal to 600 mg IM. 2/5 patients evaluable for response had stable disease at 4 months, with characteristic CT findings. Conclusion: Preliminary evidence in this study indicates activity of the combination of PKC412 and IM in IM-resistant GIST. This study is ongoing. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Novartis Novartis Novartis Novartis
Shining a Light on the Dark Side
Authors: Christine Laine, Darren B. Taichman, Michael A. LaCombe
Journal: Annals of Internal Medicine (2016)

Letters5 January 2016Shining a Light on the Dark SideChristine Laine, MD, MPH, Darren B. Taichman, MD, PhD, and Michael A. LaCombe, MDChristine Laine, MD, MPHSearch for more papers by this author, Darren B. Taichman, MD, PhDSearch for more papers by this author, and Michael A. LaCombe, MDSearch for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/L16-0016 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail IN RESPONSE:We appreciate the attention that the On Being a Doctor essay "Family Secrets" has garnered. Whether readers appreciated or were appalled by our decision to publish it, the essay has clearly generated dialogue about an important issue. Prompting such discourse was exactly why we published it.Mr. Vargas Pelaez believes that it was inappropriate for an internal medicine journal to publish an essay about an incident that occurred in an obstetrics and gynecology setting. We believe that the issues raised in this essay transcend specialty divisions. Unfortunately, this sort of inappropriate behavior is not confined to a single ... Author, Article, and Disclosure InformationAffiliations: Disclosures: Disclosures can be viewed at www.acponline.org/authors/icmje/ConflictOfInterestForms.do?msNum=M15-1144. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetailsSee AlsoOn Being a Doctor: Shining a Light on the Dark Side Christine Laine , Darren B. Taichman , and Michael A. LaCombe Shining a Light on the Dark Side Elizabeth Allemann Shining a Light on the Dark Side Alvaro F. Vargas Pelaez Shining a Light on the Dark Side Gaetan Sgro , Mark T. Gladwin , Alexander Teng , Akshata Moghe , and Shanta M. Zimmer Shining a Light on the Dark Side Shafik Dharamsi Shining a Light on the Dark Side Linda Ray Shining a Light on the Dark Side Jordan Cohen and Richard I. Levin Metrics 5 January 2016Volume 164, Issue 1Page: 70KeywordsBehaviorDisclosureObstetrics and gynecology ePublished: 5 January 2016 Issue Published: 5 January 2016 Copyright & PermissionsCopyright © 2016 by American College of Physicians. All Rights Reserved.PDF downloadLoading ...
Abstract 14158: Association Between Sleep Apnea, Snoring, Incident Cardiovascular Events and All-Cause Mortality in an Adult Population. MESA
Authors: Joseph Yeboah, Susan Redline, Craig Johnson, Russel Tracy, Pamela Ouyang, Roger Blumenthal, Gregory L Burke, David M Herrington
Journal: Circulation (2011)

Background: We assessed the association between sleep apnea, snoring, incident cardiovascular (CV) events and all-cause mortality in the Multi Ethnic Study of Atherosclerosis (MESA) cohort. Methods...
Abstract 10919: Plasma Carnitine Level in Heart Failure Patients With Sleep Disordered Breathing
Authors: Makiko Miyata, Akiomi Yoshihisa, Takayoshi Yamaki, Syoji Iwaya, Takashi Owada, Satoshi Suzuki, Masayoshi Oikawa, Koichi Sugimoto, Kazuhiko Nakazato, HItoshi Suzuki, Shu-ichi Saitoh, Yasuchika Takeishi
Journal: Circulation (2012)

Background: Carnitine plays an important role in the utilization of fatty acids and glucose in the myocardium. Although myocardial carnitine level decreases in the failing heart, it is still unclea...
Phase I pharmacokinetic and pharmacodynamic evaluation of the vascular disrupting agent OXi4503 in patients with advanced solid tumors.
Authors: M. Zweifel, D. M. Patterson, A. R. Padhani, M. R. Middleton, P. Price, M. R. Stratford, P. Ross, S. Halford, Z. Goldberg, G. J. Rustin
Journal: Journal of Clinical Oncology (2010)

2594 Background: OXi4503 (combretastatin A1 phosphate, CA1P) is the prodrug of OXi4500 (CA1), a tubulin binding vascular disrupting agent (VDA). Preclinical studies show that OXi4503 has single-agent activity resulting in greater reduction in blood flow than the related drug CA4P. Methods: OXi4503 (0.06 to 15.4 mg/m2 dose escalation) was given IV over 10 min on day 1, 8, and 15 every 28 days (=1 cycle) to patients with advanced solid tumors. Dynamic contrast enhanced (DCE) MRI for the assessment of changes in blood flow (2 baseline and 3 post-dose scans at 4 h, 24 h, and 56 d; blood oxygenation level dependent MRI (R2*) measurements hourly for up to 4 h after the first OXi4503 infusion) was performed. Accrual will be completed in January 2010. Results: 42 patients (22 F, 20 M) have received 236 OXi4503 infusions. Common adverse events were hypertension, tumor pain, fatigue, myelosuppression and nausea. Drug-related dose limiting toxicities (DLTs) were seen in both patients at 15.4 mg/m2 (atrial fibrillation and bowel fistula with septic shock secondary to tumor lysis) and 2 patients at 11 mg/m2 (CTCAE grade 3 hypertension and visual disturbances that were possibly related to the hypertension). Dose levels of 12.5 mg/m2 and 14 mg/m2 were explored following the introduction of amlodipine as prophylaxis to prevent hypertension. PK showed dose-dependent linear increases in peak plasma concentrations and AUC of both OXi4503 and OXi4500, with OXi4500 concentrations comparable to those at the MTD in pre-clinical toxicology. 7 of 16 (44%) of evaluable patients showed MRI changes consistent with VDA (either R2* or transfer constant) activity. A drug dose–vascular response relationship was shown by both imaging parameters, with significant blood deoxygenation apparent at 1 h. Best observed responses include one RECIST partial responder at 11 mg/m2 and one GCIG CA125 response at 14 mg/m2 in patients with epithelial ovarian cancer. Conclusions: OXi4503 is well tolerated up to 14 mg/m2 when amlodipine is given as prophylaxis and efficacy does not appear to be compromised. OXi4503 shows single-agent clinical and functional imaging activity. The recommended phase II dose will lie between 11 and 14 mg/m2. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration OXiGENE OXiGENE OXiGENE
Nicotinamide found to reduce the rate of nonmelanoma skin cancers in high‐risk patients
Authors: Mary Kay Barton
Journal: CA A Cancer Journal for Clinicians (2016)

Key Points Daily nicotinamide significantly reduced the incidence of nonmelanoma skin cancers in high‐risk individuals. It is reasonable to recommend nicotinamide in high‐risk individuals along with continued sunscreen use and regular skin checks in motivated patients. Further studies including longer follow‐up and a wider population of patients to assess for any unforeseen safety issues as well as efficacy are indicated.
Prevalence of allergic rhinitis in Russian adolescents
Authors: Anna Tomilova, Leyla Namazova-Baranova, Raisa Torshkhoeva, Elena Vishneva, Ludmila Ogorodova, Ivan Deev, Julia Levina
Journal: European Respiratory Journal (2011)

The results were obtained by two centres in Russia (Moscow and Tomsk) as part of the international epidemiological study under the GA 2 LEN programme. The total number of polled adolescents aged 15 to 18 was 12,803 with 2014 subjects, included in the statistical analysis (1004 subjects in Moscow, and 1010 in Tomsk). The male subjects accounted for 44.6% and female subjects for 55.4%. The age was 15.48±0.02 years. The cumulative disease incidence was determined as a totality of all the disease cases registered during the past year and in the previous follow-up period. Prevalence is the registered disease cases in which primary visits took place during the calendar year.  The cumulative allergic rhinitis (AR) incidence totaled 34.2%, which significantly exceeds official statistics. The female subjects indicated much more often the presence of AR compared to the male subjects (37.35% and 30.42% respectively at p=0,044). The symptoms of the ongoing AR were found in 86.45% of the total respondents who had indicated the cumulative rhinitis incidence. The follow-up results indicate significant variance from the official statistics (in 2008, the official AR incidence in Moscow was 599.2 per 100,000).  The percentage of the female subjects with AR symptoms, however, was reliably higher than that in Moscow (p=0.042), with the cumulative rhinitis incidence registered more often compared with the ongoing AR both for the entire population and for Moscow (at p=0.0125 and p=0.026 respectively). Prevalence of symptoms for allergic rhinitis was significantly higher than the diagnosed disease forms. The data obtained using standardised tools will help optimise the existing programmes for preventing and diagnosing allergic rhinitis.
Phase I dose escalation study of pomalidomide in combination with gemcitabine in patients (pts) with untreated metastatic carcinoma of the pancreas
Authors: J. R. Infante, S. F. Jones, J. Bendell, D. Spigel, J. Barton, J. Zubkus, C. Byrne, P. Griner, C. Weekes, W. A. Messersmith, H. A. Burris
Journal: Journal of Clinical Oncology (2009)

e15539 Background: Pomalidomide is an IMiD immunomodulatory compound that is synergistic with gemcitabine in preclinical models. Pomalidomide has immuno-stimulatory properties and effects on the tumor microenvironment including inhibition of inflammatory mediators, stromal cell support, endothelial cell function, and angiogenesis. The primary objective is to determine the maximally tolerated dose (MTD) and evaluate the safety profile of pomalidomide in combination with gemcitabine. Methods: Eligibility included pts with untreated metastatic pancreatic cancer, adequate organ function, ECOG 0–1, and willingness to take prophylactic anticoagulation with aspirin, low-dose coumadin, or low molecular weight heparin. Gemcitabine 1,000 mg/m2 was given as a 30 min IV infusion on days 1, 8, and 15 of a 28 day cycle. Pomalidomide was given orally, daily for 21 days of a 28 day cycle. 3–6 pts were enrolled to increasing dose cohorts of pomalidomide (2, 3, 5, 7, and 10 mg/day) until dose-limiting toxicity (DLT) was seen in ≥2 of 6 pts. Results: As of 15-Dec-2008, 22 pts received ≥ 1 dose of pomalidomide. No DLT's were observed for 2–7 mg and 3 pts are currently on study in the 10 mg cohort. Neutropenia occurred in 12 pts, 8 were grade 3–4 events. There was 1 DLT of grade 3 neutropenic fever in the 10mg cohort. Thrombocytopenia events (9) were grade 1–2. Non- hematologic events were grade 1–2, the most common being rash (11), fatigue (10), nausea (6), and diarrhea (6). The rash is mild, erythematous, nonpruritic, of limited distribution, and reversible. 2 pts developed DVT (1 during cycle 2 and 1 cycle 4). Of the 16 pts evaluable for response, 1 pt has a confirmed PR and a CA 19–9 that normalized from 157 to &lt;3. 4 additional pts have had minor radiographic responses between 10 and 29%. 10 of 16 pts have had a ≥ 60% decrease in CA19–9 from baseline. Only 2 pts came off study for early progression at the end of cycle 2. Conclusions: Dosing of pomalidomide daily for 21 days in combination with gemcitabine 1,000 mg/m2 given IV on day 1, 8, and 15 of a 28 day cycle was well tolerated and has promising clinical activity in patients with metastatic pancreatic cancer. The RP2D of pomalidomide in combination will be 7 or 10 mg. [Table: see text]
Capecitabine, irinotecan and celecoxib (XIC), for patients with unresectable/metastatic cholangiocarcinoma
Authors: J. L. Bibb, F. C. Lee, M. Roach, G. Parasher, G. Heywood
Journal: Journal of Clinical Oncology (2005)

4265 Background: There is no known effective chemotherapy regimen for patients with unresectable/metastatic cholangiocarcinoma. We are here to report a single institution, retrospective chart review on using a combination of irinotecan, capecitabine, and celecoxib in treating these patients. Methods: From 9/03 to 11/04, 8 chemotherapy naive patients with a tissue diagnosis of unresectable/ cholangiocarcinoma were seen and treated with a regimen consisting of irinotecan 120mg/m2 on D1, capecitabine 1500mg/m2 D1–14 and celecoxib 200mg bid daily, Q21 days. Results: Six females and two males, age 56–63 (median age=60), performance status(PS) between 0–2. A total of 64 treatments were given. Baseline CA 19–9 ranged from 86.9 - 6068 u/ml (normal < 33). 7 patients evaluable for CA19–9 response and treatment toxicity. A decline in CA19–9 was seen in 100% (5/7 > 80% decline). CT scan: 2/7 had stable disease and 2/7 had a minimum response (<20% decrease in target tumor size). Toxicity: diarrhea: 5/7 grade 0, 2/7 grade 1; hand-foot syndrome: 6/7 grade 0, 1/7 grade 1; anemia: 1/7 grade 0, 4/7 grade 1, 2/7 grade 2; neutropenia: 4/7 grade 0, 1/7 grade 1, 2/7 grade 2. No other grade III/IV non-hematological toxicity. All patients were alive as of 12/09/04 (1 - 15 months from initiation of treatment). Two patients remain working full time. Median response duration and median survival data have not matured. Conclusions: XIC is well tolerated in patients with unresectable/metastatic cholangiocarcinoma and provides good palliative effects. A prospective phase II trial study with a dose-escalating scheme for irinotecan and quality of life assessment is being planned. No significant financial relationships to disclose.