tbuckley/cabot-search huggingface dataset:
Phase II trial of vinflunine (VFL) in sensitive and refractory relapsed small-cell lung cancer (SCLC): Updated results
Authors: S. D. Lunin, D. R. Spigel, J. D. Hainsworth, D. M. Waterhouse, J. R. Infante, D. A. Yardley, H. A. Burris, E. R. Vazquez, C. Farley, F. A. Greco
Journal: Journal of Clinical Oncology (2008)

19028 Background: VFL is a new microtubule inhibitor with preclinical activity in SCLC. In this multicenter, community-based phase II trial, we evaluated VFL in patients (pts) with sensitive and refractory relapsed SCLC. Methods: This trial had a 2-stage design with the primary aim of achieving an objective response rate (ORR) of 20% in platinum sensitive pts (α .05, β .20), and a secondary aim to assess the ORR in refractory relapsed pts. Pts with ECOG PS 0–2, measurable disease, and signed informed consent were eligible. All pts received VFL 320mg/m2 IV day 1 every 21 days for up to 6 cycles, with restaging every 6 weeks (per RECIST criteria). Results: Between 3/06 and 4/07, 51 pts were enrolled. The median follow-up is 12 months (range 8 - 16 months). Pt characteristics: median age 63 years (range 37 - 85 years); male, 55%; ECOG PS 0–1, 84%; and sensitive relapse (n= 26) 51%. Overall, 3 pts were not evaluable due to compliance (1) and treatment-related toxicity (2). Among sensitive relapsed pts, there were 3 partial responses (PR), ORR 12% (95% CI 3% - 31%). 9 pts (36%) had stable disease (SD) and 12 pts (48%) had progressive disease (PD). Response durations: 2, 2.5, and 3.9 months. Among refractory relapsed pts (n=25) there were 4 PRs (ORR 16%), 6 pts (24%) with SD, and 14 pts (56%) with PD. Response durations: 0.3, 1.1, 1.7, and 2.7 months). The median progression-free survival and overall survival for all patients were 2.3 months and 4.9 months, respectively. Grade (G) 3 non-hematologic toxicity in >5%: constipation (8%), dyspnea (6%), fatigue (18%), nausea (8%), and pain (6%), with no grade 4 toxicities. G3/4 hematologic toxicity included neutropenia (33%) and thrombocytopenia (10%). There were 2 treatment-related deaths due to infection. Conclusions: VFL appears to have activity in relapsed SCLC, including refractory relapsed pts. G 3/4 non-hematologic side-effects were uncommon; however neutropenia and infection are potentially serious toxicities in this pt population. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration Bayer, Genentech Bristol-Myers Squibb Bristol-Myers Squibb, Eli Lilly and Company, Genentech, GlaxoSmithKline, GPC Biotech, sanofi-aventis
Dextromethorphan phenotyping as a test for prediction of tamoxifen (TAM) activation in breast cancer patients receiving adjuvant hormone therapy.
Authors: Milena Gusella, Laura Bertolaso, Felice Pasini, Yasmina Modena, Antonio Bononi, Anna Paola Fraccon, Donatella Da Corte, Elisabetta Cretella, Caterina Modonesi, Francesca Vastola, Linda Nicolardi, Cristina Pegoraro, Giovanni Rosti, Antonella Brunello, Romana Segati, Emilia Durante, Cristina Falci, Concetta Raiti, Elvira Rampello, Robeto Padrini
Journal: Journal of Clinical Oncology (2012)

e13019 Background: TAM is mainly metabolized by CYP2D6 to form its most active metabolites, 4hydroxy-tamoxifen (4OH-T) and endoxifen (END). Because of its long half-life, steady state is reached after around 4 months of continuous intake. The wide variable inter-patient activity of CYP2D6 might influence drug efficacy. A multi-institutional study in north Italy is evaluating the relationship between END levels and outcome. As a part of it, we investigated the role of dextromethorphan (DM), a probe drug for CYP2D6 enzymatic activity, as a potential phenotyping test for TAM activation. Methods: Twenty-nine breast cancer patients (75% postmenopausal) on adjuvant TAM therapy (20 mg/die) were investigated. They received a single dose (15 mg) of oral DM before starting TAM and their urines were collected over the10 following hours. Simultaneous quantitative determination of DM and its metabolite dextrorphan (DO) was performed in urines to estimate their log transformed metabolic ratio (LMR=logDM/DO). After 4 months a blood sample was collected to characterize TAM exposure at steady state; plasma levels of TAM, END, 4OH-T and the non active END precursor N-desmethyltamoxifen (NDT) were quantified by HPLC. Linear regression analysis and t test were performed for correlating LMR and drug plasma levels. Results: LMR varied between -2.15 and 0.90 (median: -1.37) while steady state plasma levels of END varied between 1.9 and 15.0 ng/ml (median: 4.36) and 4OH-T between 0.9 to 3.1 ng/ml (median:1.72). A significant correlation (r = 0.56; p= 0.0013) was found between LMR and END plasma concentrations. The patients with high LMR (&gt; median value), compared to patients with low LMR, had lower END (3.7 vs 7.5 ng/ml, p=0.0003), lower 4OH-T (1.6 vs 2.1 ng/ml, p=0.04) and, accordingly, higher NDT (291.2 vs 198.2 ng/ml, p=0.025). Conclusions: DM/DO urine ratio obtained before starting therapy correlates with TAM biotransformation activity and can predict steady state active metabolites exposure in individual patients. This phenotyping test is fast, simple and unexpensive and could contribute to the personalization of adjuvant breast cancer treatment. Funded by Regione Veneto.
Improved Functional Outcome After Additional Catheter-Directed Thrombolysis for Acute Iliofemoral Deep Vein Thrombosis: Results of a Randomized Controlled Clinical Trial (The CaVenT Study)
Authors: Tone Rønnaug Enden, Ylva Haig, Nils-Einar Kløw, Carl Erik Slagsvold, Leiv Sandvik, Waleed Ghanima, Geir Hafsahl, Pål Andre Holme, Lars Olaf Holmen, Anne Mette Njaastad, Gunnar Sandbaek, Per Morten Sandset
Journal: Blood (2011)
Caregivers' accuracy in reporting patients' symptom: A preliminary report.
Authors: Paola Langer, Pedro Emilio Perez-Cruz, Cecilia Carrasco Escarate, Pilar Bonati, Bogomila Batic, Laura Tupper, Marcela Gonzalez Otaiza
Journal: Journal of Clinical Oncology (2016)

64 Background: Improving symptom control during end of life (EOL) is a core goal of palliative care. When patients are not able to report their symptoms, caregivers (CG) report symptom intensity as surrogates. Data show that there is good agreement between patients and CG in reporting symptom intensity. However, little is known about factores that influence CGs’ accuracy. The aim of the study was to determine CG accuracy of advanced cancer patients’ symptoms and to identify CG factors that could modify it. Methods: In this prospective study, patients with advanced cancer enrolled in the National Program of Palliative Care at a public Hospital in Santiago, Chile and their CGs independently scored ten patients’ symptoms using the Edmonton Symptom Assessment Scale (ESAS). Correlation between patient and CG scores were estimated for each symptom. Differences between patient and CG scores were calculated for each symptom and were transformed into positive values. A continuous variable was created with the sum of all the differences as an indicator of caregiver overall accuracy, with smaller scores meaning better accuracy. CG depression, anxiety (HADS) and burden (ZARIT) were also assessed. Results: 36 patients and their CG were included in this preliminary analysis. Mean patient age was 64, 20 (56%) females, 13 (36%) had GI cancer, 7 (19%) lung cancer and 16 (45%) other. Mean caregiver age was 53, 25 (69%) female. We found positive correlations between patients’ and caregivers’ assessment of pain, fatigue, nausea, anorexia, dyspnea, depression and insomnia (r &gt; 0.3 and p &lt; .05 for each symptom). CG accuracy ranged between 10 and 44 points (mean 25, standard deviation 9) and was not associated with CG age, gender, depression, anxiety or burden. CG accuracy was negatively associated with CG worrying thoughts as assessed by one of the HADS questions (Coef -3.99, p = .015), meaning that CG were more accurate when their worrying thoughts were higher. This association remained significant when adjusted by CG depression, anxiety and burden. Conclusions: CG are more accurate in reporting patient symptoms when their levels of worrying thoughts are higher. This information may have implications in interpreting CG report during EOL.
Designing a multidisciplinary oral chemotherapy education and monitoring program.
Authors: Sharon Lane, Kimmie Ng, Robin Sommers, Carole Kathleen Dalby, Susanne Conley, Patricia Rizzo, Janet Bagley, Christy Harris, Frances Fuller, Phuong Nguyen, Audrea Szabatura
Journal: Journal of Clinical Oncology (2014)

146 Background: In 2013 ASCO and ONS published guidelines to promote safe practices for oral chemotherapy use. These agents can have significant toxicities and pose safety risks without proper adherence. Guided by the ASCO/ONS recommendations, Dana-Farber Cancer Institute (DFCI) designed a program to provide comprehensive patient education and adherence monitoring. Methods: To address patient safety risks associated with oral chemotherapy use, a multidisciplinary team assembled to design a process for timely and appropriate patient education and adherence monitoring. Physicians, Nurse Practitioners or Physician Assistants initiate education by reviewing the dosing schedule, side effects and providing a standard education sheet. Within 24 hours, a pharmacist contacts the patient and completes a teaching session utilizing a template based upon the MOATT Tool, a teaching tool developed by the Multinational Association of Supportive Care in Cancer. The MOATT Tool includes a review of the dosing schedule, side effects and management, drug handling, drug/food interactions and practice contact information for questions. Lastly, within five days of therapy initiation, a nurse calls the patient to reinforce education and to assess toxicity and adherence. To evaluate the effectiveness of the program, chart audits and patient satisfaction surveys were conducted. Results: To date 78% of patients started on oral chemotherapy have received a teaching session and 73% have received a follow up adherence call. Patient satisfaction surveys conducted demonstrate that 100% (N=12) of patients strongly agreed with the following statement; “following my counseling session with the Dana-Farber pharmacist, I understood how and when to take my oral chemotherapy medication(s)” and 94% agreed with the statement; “overall I feel that the oncology nurse phone session provided me with useful information.” Conclusions: Implementing a standard patient education and adherence monitoring program for patients initiating oral chemotherapy is essential to guarantee safe patient care. Compliance monitoring at the disease and provider level is necessary to ensure continual quality improvement.
Taking care of the patient with cancer: How treatment practices vary by the experience of the treating oncologist.
Authors: K. R. Hoffman
Journal: Journal of Clinical Oncology (2011)

e19665 Background: Oncologists have multiple choices in managing their patients. With biologic agents unique toxicites are being seen. These agents require new basic science knowledge and diagnostic skills. As oncologists age and get further away from their academic training, just how comfortable are they in caring for patients and how clinically competent are they? Are oncologists taking care of the entire patient or are they just giving drugs to treat their patient’s disease? Methods: 37 of the 50 invited community oncologists participated in this study. There were 40 questions with 10 patient vignettes dealing with various medical and psychosocial issues involved in the treatment of advanced stage cancer. An analysis was done between oncologists in practice less than 10 years (15), from 10 to 20 (8) and over 20 (14). Results: The younger physicians better understood the mode of action of the newer agents. All respondents felt comfortable using them even as the newer toxicities required care from other specialties. Attendence at ASCO was not a high priority for any group.The older oncologists thought that ASCO attendence had become “irrelevant” due to a host of reasons. All respondents felt that CME courses “on-line” and local and regional meetings gave them the information that they needed to care for their patients. Their understanding of statistical end points in clinical trials was equally poor. All groups used consultants for cardiopulmonary issues while the older physicians were more comfortable handling the septic neutropenic patient. The younger physicians were uncomfortable and less knowledgeable in dealing with psychosocial issues. They relied quite heavily on others while the experienced physicians handled these issues with little difficulty or stress. Conclusions: The more experienced oncologist were more comfortable dealing with palliative and end of life issues. They also used subspecialty colleagues less often by doing more “general internist” work. Attendence at the ASCO annual meeting is of much less importance as many of the respondents felt that “cost-benefit” strongly favored not attending but going to a post-ASCO review course and other locoregional events.
Quality and value implications of NCCN-compliant use of maintenance rituximab for patients with low-grade NHL.
Authors: Dinah Faith Q. Huff, Charles L. Bennett, William S. Shimp, Anmol Baranwal, Avinash Mamgain, Marc L. Fishman, Sharon Davis, Jurgen Kogler, Anna E. Schorer, Laura Rose Bobolts, Melissa Armitage, William J. Hrushesky
Journal: Journal of Clinical Oncology (2014)

36 Background: Rituximab maintenance for indolent, incurable non-Hodgkin lymphoma (NHL) remains controversial. NCCN supports maintenance rituximab for a span of up to two years as an alternative to watchful waiting following induction therapy. At least a dozen scientific papers have been published describing rituximab maintenance results; none has demonstrated overall survival benefit. The strongest data support comes from the PRIMA phase III trial which showed an increased PFS but no survival advantage. Increased toxicity, however, is clear and can be serious. Reports of progressive multifocal leukoencephalopathy, a rapidly fatal neurodegenerative disease, should be of especial concern to patients whose disease course can span many years. Oncology Analytics (OA) enhances cancer care quality and value by providing oncology decision-support to providers in SE USA. We hypothesized that the use of maintenance rituximab in this area of the country produces profound cost and real risk for a highly uncertain benefit to this population. Methods: We reviewed all requests for rituximab maintenance for low-grade NHL submitted by oncology practices to a major health insurer in one US region from Jul 2009-May 2014. We calculated the cumulative cost for blanket approval of such requests and the savings associated with our decision-support discussions of this questionable but NCCN-compliant practice. Results: 470 requests for maintenance rituximab for low-grade NHL were initiated within this 59-month span. The proportion of maintenance rituximab requests relative to the total chemotherapy requests decreased consistently over time, from 4.5% in the first six months of OA involvement in 2009, down to 1.5% in May 2014. The annual cost of rituximab maintenance, which depends on the dose schedule, ranges from about $30,000 to $40,000 per year. Additionally, we discovered many rituximab maintenance requests for durations exceeding two years without evidence-based support, most of which were rescinded after OA intervention. Conclusions: Ongoing OA intervention reduces risk of toxicity and enhances the quality and value of cancer care for these patients.
A consolidated screening tool for supportive oncology needs and distress.
Authors: Christine B. Weldon, Nancy Vance, Amy Scheu, Lauren Allison Wiebe, Shelly S. Lo, Catherine Deamant, Betty Roggenkamp, Urjeet Patel, Paramjeet Khosla, Patricia A. Robinson, Frank J. Penedo, James Gerhart, Teresa Lillis, William Dale, Ana Gordon, Eileen Knightly, Rosa Berardi, Julia Rachel Trosman
Journal: Journal of Clinical Oncology (2017)

47 Background: The IOM 2013 Report recommends that supportive oncology care start at cancer diagnosis; the Commission on Cancer (CoC) Standard 3.2 requires distress screening and indicated action. Screening tools are not standardized across institutions and often address only a portion of patients’ supportive oncology needs. Methods: A collaborative of 100+ clinicians, funded by The Coleman Foundation, developed a patient-centric consolidated screening tool based on validated instruments (NCCN Distress, PHQ-4, PROMIS) and IOM and CoC. The screening tool was piloted at 6 practice-improvement cancer centers in the Chicago area (3 academic, 2 safety-net, 1 public). Patients, providers assessing patients’ screening results (assessors), and providers receiving referrals (providers) were surveyed after use of the screening tool. Descriptive statistics were used to assess effectiveness of the tool. Results: Responders included 175 patients, 81 assessors, and 26 referral providers (social workers, chaplains, subspecialists). The majority of patients (160/175, 91%) completed the screening in &lt;10 minutes, across all patients the screening tool averaged 4 ½ minutes. Most assessors (59/77, 76%) spent &lt;5 minutes reviewing screening results. Most patients, assessors, and providers reported the screening tool asked the “right questions”. Assessors reporting partial relevance of some screening questions for 34% (26/77) of patients, uncovered ≥ 1 relevant needs for 96% (25/26) of those patients (p = 0.002). Conclusions: Use of a consolidated supportive oncology screening tool across multiple institutions is feasible, identified unmet patient needs, and was beneficial for assessors and providers. As the tool is adopted by collaborating institutions, variability in supportive oncology screening practices may decline, thus improving patient care. The tool has implications for quality improvements and national dissemination. [Table: see text]
Patterns of comorbidity among older U.S. patients with non-Hodgkin lymphoma.
Authors: Laura Hester, Steven I. Park, Jennifer Leigh Lund
Journal: Journal of Clinical Oncology (2016)

304 Background: Evidence suggests that the number and type ofcomorbidities at cancer diagnosis influences cancer treatment and mortality, especially among older patients.We sought to describe comorbidity patterns and identify how patterns predict all-cause mortality among older non-Hodgkin lymphoma (NHL) patients. Methods: Using the linked Surveillance, Epidemiologic, and End Results (SEER)-Medicare databases, we identified patients aged &gt; 66 with a first diagnosis of stage I-IV NHL from 2007-2009. Codes for individual comorbidities in the Charlson Comorbidity Index (CCI) were identified in the 12 months before NHL diagnosis, during which patients were required to have continuous Medicare Parts A, B, and D enrollment and no managed care. The prevalence of single and concurrent comorbidities was calculated. Medicare enrollment files contained vital status. We used multivariable Cox proportional hazard models to estimate adjusted hazard ratios (aHR) for all-cause mortality in each comorbidity group versus no comorbidity controlling for age, sex, race/ethnicity, stage, tumor growth category, and other comorbidities. Results: Among 4901 older NHL patients, 52% had ≥ 1 comorbidity and 26% had a CCI &gt; 2. The most prevalent comorbidities were diabetes (25%), chronic obstructive pulmonary disorder (COPD) (16%), and congestive heart failure (CHF) (12%). All-cause mortality was greater among patients with CHF (aHR = 1.44; 95%CI = 1.26, 1.65), diabetes (aHR = 1.16; 95%CI = 1.03,1.29), or dementia (aHR = 1.20; 95%CI = 1.03, 1.41) compared to those without each comorbidity. More than half of diabetes patients, two-thirds of COPD patients, and three-quarters of CHF patients had &gt; 1 additional non-cancer comorbidity. All-cause mortality was higher among NHL patients with CHF who had co-occurring COPD (aHR = 1.56; 95%CI = 1.19, 2.05), diabetes (aHR = 1.66; 95%CI = 1.29, 2.14), or both COPD and diabetes (aHR = 2.61; 95%CI = 1.97, 3.46). Conclusions: Comorbidity is common among older, newly-diagnosed NHL patients and should be carefully considered when making treatment decisions. Given the known cardiotoxicity of the main NHL chemoimmunotherapy, providers should discuss comorbidity management, particularly for CHF, before initiating therapy.
Long term follow up in relapsed Hodgkin’s disease (HD): Updated results of the HD-R1 study comparing conventional chemotherapy (cCT) to high-dose chemotherapy (HDCT) with autologous haemopoetic stem cell transplantation (ASCT) of the German Hodgkin Study Group (GHSG) and the Working Party Lymphoma of the European Group for Blood and Marrow Transplantation (EBMT)
Authors: N. Schmitz, H. Haverkamp, A. Josting, V. Diehl, B. Pfistner, A. M. Carella, M. Haenel, F. Boissevain, C. Bokemeyer, A. H. Goldstone
Journal: Journal of Clinical Oncology (2005)

6508 Background: With HDCT+ASCT representing the standard treatment of relapsed HD long-term follow-up of randomized trials comparing cCT with HDCT+ACST is important. Methods: 161 patients (pts) with biopsy proven relapse of HD aged 16–60 years were randomized to 2 cycles of dexamethasone (DEXA), BCNU, etoposide, cytarabine and melphalan (Dexa-BEAM) followed by 2 further cycles of Dexa-BEAM (arm A) or 2 cycles of high-dose BEAM+ASCT (arm B) between 2/1993 and 9/1997. Only chemosensitive pts (complete or partial remission after first 2 cycles) were eligible for analysis (n=56+61). 150 chemosensitive pts were needed to show an improvement of 20% in 2 year freedom from treatment failure (FFTF) with a power of 0.8. Results: With comparable baseline characteristics and median follow-up of 83 months 7-year-FFTF was 32% (95% confidence interval (CI) 20%, 45%) in arm A and 49% (CI 36%, 42%) in arm B (logrank p=0.02). Subgroup analysis for 7-year FFTF showed differences in early first (12% arm A vs. 42% arm B, p<0.01) and late first relapse (44% arm A vs 63% arm B, p=0.07) but not for multiple relapse (32% arm A vs. 27% arm B, p=0.57). Overall survival (OS) at 7 years was 56% (CI 42%, 69%) vs. 57% (CI 43%, 71%). Causes of death in all randomized patients (n=69/161) including secondary neoplasias (3 AML, 1 solid tumor) are comparable. Conclusion: These results confirm that FFTF after HDCT+ASCT is superior to cCT in first relapse whereas no difference between HDCT and cCT was seen for patients with multiple relapses. OS did not significantly differ between HDCT/ASCT and cCT. No significant financial relationships to disclose.