tbuckley/cabot-search huggingface dataset:
Significant improvements of psychosocial parameters by an educational intervention program for patients with early breast cancer
Authors: E. Andritsch, S. Zloklikovits, V. Ladinek, S. Stanzer, B. Janesch, T. Augustin, H. Samonigg, T. Bauernhofer
Journal: Journal of Clinical Oncology (2008)

9591 Background: The aim of this study was to examine the influence of a specific psychosocial educational group intervention (Learning to live with Cancer program; G. Grahn, Eur J Cancer Care 1996) on psychosocial parameters in early breast cancer patients. Methods: Fifty-one postmenopausal patients with operated primary breast cancer stage I - III, within two years of diagnosis, were entered into this open randomized trial. Patients were randomized to either receive an eight-weeks-psychosocial intervention upfront or after a waiting period of six months. A group with immediate psychosocial intervention, a control waiting group during its waiting period and healthy volunteers were compared using standardized questionnaires: EORTC QLQ-C30 (global health status), BDI (depression), STAI (state and trait anxiety), SOC (sense of coherence) as well as a semi-structured interview. All participants were evaluated at three different time points: baseline (t1), after an eight-weeks-period (t2), follow-up after further eight weeks (t3). To test the efficiency of the intervention program, repeated measures MANOVAs were computed for each group. Results: For the intervention group (n=29), significant improvements were found for the global health status (t1: 5,2±1,3; t3: 5,8±0,9; p=.010), state anxiety (t1: 30,2±8,2; t3: 25,9±9,4; p=.011), trait anxiety (t1: 33,9±7,9; t3: 26,6±11,1; p=.000) and sense of coherence (t1: 67,8±9,15; t3: 70,3±9,5; p=.038). In line with these results the depression scores improved after the intervention but not significantly. Patients in the control waiting group (n=22) showed no significant changes over the three time points except for the global health status which declined from t1 to t2 (t1: 5,3±0,1; t2: 4,6±1,3; p=.006). For the healthy volunteers (n=26) the parameters remained constant over the time with only two exceptions (state and trait anxiety). Conclusions: The efficacy of the Learning to live with Cancer intervention program to significantly improve psychosocial parameters in patients with early breast cancer warrants inclusion of this program in the daily clinical practice. No significant financial relationships to disclose.
Long-Term Follow-up of a Phase 1 Study of Idelalisib (ZYDELIG®) in Combination with Anti-CD20 Antibodies (Rituximab [R] or Ofatumumab [O]) in Patients with Relapsed or Refractory Chronic Lymphocytic Leukemia (CLL)
Authors: Richard R. Furman, Sven de Vos, Jacqueline C. Barrientos, Marshall T. Schreeder, Ian W. Flinn, Jeff P. Sharman, Thomas E Boyd, Nathan Fowler, John P. Leonard, Kanti R. Rai, Yeonhee Kim, Anthony Viggiano, Thomas M. Jahn, Steven E. Coutre
Journal: Blood (2014)
Epoetin-alpha reduces red blood cell transfusions (RBC) in high-risk breast cancer patients with adjuvant dose-dense, sequential chemotherapy with epirubicin (E), paclitaxel (T) and cyclophosphamide (C) (ETC)
Authors: U. Michael, C. Jackisch, M. S. Lenhard, A. Du Bois, H.-J. Lueck, C. Thomssen, W. Kuhn, C. Kurbacher, U. Nitz, R. Kreienberg, V. J. Möbus
Journal: Journal of Clinical Oncology (2005)

613 Background: Dose-dense chemotherapy improves DFS and OS in breast cancer patients but leads to a higher number of RBC transfusions. We analyzed the influence of Epoetin-alpha in dose-dense sequential chemotherapy with ETC on the amount of blood transfusions and median Hb value during treatment. Methods: From 12/98 until 4/03, 1284 pts were recruited for a multi-center phase-III trial. Breast cancer pts with at least 4 involved axillary lymph nodes and below 65 years of age were eligible. In the standard arm, pts received 4 courses of conventionally dosed epirubicin/cyclophosphamide (90/600mg/m2) followed by 4 courses of paclitaxel (175 mg/m2) at 3 weeks interval (q3wks). In the experimental arm, pts were given three courses each of epirubicin (150mg/m2), paclitaxel (225mg/m2) and cyclophosphamide (2500mg/m2) (ETC) (q2wks). A second randomization ± Epoetin-alpha was performed (150 IU/kg/sc three times weekly). Results: In 05/04, 1143 (98%) pts were fully evaluable. Risk factors were equally distributed in both arms, no treatment-related deaths occurred during therapy. Pts treated in the dose-dense arm (ETC) suffered more often from hematological toxicity(p<0,0001). Anemia was seen significantly more often in the dose-dense arm (ETC) without Epoetin-alpha treatment than with Epoetin-alpha treatment (p < 0.0001). Altogether, 11% of all patients were treated with RBC transfusion. Standard EC->T treatment resulted in 1% RBC transfusion, but 28% in the ETC arm without vs. 12% in the ETC arm with Epoetin-alpha (p < 0.0001). Despite this significantly higher rate of transfusions the median Hb value dropped from 12,8 g% at cycle 1 to 10,7 g% at cycle 9 without Epoetin-alpha. In contrast it remained stable with Epoetin-alpha (12,4 g% at cycle 1 and 9). So far, disease free (DFS) and overall survival (OS) were similar in the ETC ± Epoetin alpha arm (p=0,98). Conclusion: The dose-dense adjuvant ETC-regimen improves DFS and OS in high-risk breast cancer pts (≥ 4 +LN). Epoetin-alpha significantly reduced the number of RBC transfusions and prevented a decline of the median Hb value without influence on DFS and OS. No significant financial relationships to disclose.
Efficacy of induction with cybord in newly diagnosed multiple myeloma
Authors: C. B. Reeder, A. K. Stewart, J. G. Hentz, P. L. Bergsagel, N. A. Pirooz, R. Fonseca, C. Chen, S. Trudel, D. Reece, V. Kukreti
Journal: Journal of Clinical Oncology (2008)

8517 Background: The combination of oral cyclophosphamide, bortezomib and dexamethasone (CyBorD) is active in multiple myeloma (MM) producing rapid responses. The goal of this study was to determine the depth of that response in newly-diagnosed patients with multiple myeloma as assessed by CR, nCR and VGPR after 4 cycles of therapy. Methods: Patients with newly diagnosed MM were eligible if they had measurable or evaluable disease, were >18 years of age, had an ECOG PS <3 and were able to give informed consent. Treatment consisted of a single arm of cyclophosphamide 300mg/m2 po days 1, 8, 15, 22, bortezomib 1.3 mg/m2 IV days 1, 4, 8, 11 and dexamethasone 40mg po days 1–4, 9–12, and 17–20 of a 28 day cycle. A total of 4 cycles was planned with the goal of proceeding on to stem cell transplant. Growth factors were allowed after cycle 1. The primary endpoint was complete response with secondary endpoints of ORR, PFS and toxicity. Results: 33 patients have been enrolled and 23 are evaluable for response and toxicity at the time of writing. Patient characteristics included mean age of 60, 43 % female, and ISS stage II/III in 35/26 %. Prior to transplant the ORR is 100 % with 85 % achieving at least a VGPR. 64 % had a CR or nCR. Responses occurred rapidly with a mean reduction in M-Protein of 66 % and 83 % after 1 and 2 cycles. Grade 3 toxicities included neutropenia in 20%, thrombocytopenia in 9 %, hyperglycemia in 17 % and peripheral neuropathy (PN) in 5 %. Gr 1–3 PN occurred in 69%. There was no grade 5 toxicity. All patients that elected to proceed on to transplant were able to undergo successful stem cell harvests. Conclusions: The induction regimen CyBorD is highly active in the treatment of newly diagnosed MM and produces very good and complete responses exceeding those seen with other induction regimens, mimicking that seen with high-dose therapy and stem cell transplantation. The main toxicity is peripheral neuropathy. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration Celgene, Halozyme, Millennium Celgene, Millennium Millennium, Pfizer Oncology
International multicenter randomized phase III study of first-line erlotinib (E) followed by second-line cisplatin plus gemcitabine (CG) versus first-line CG followed by second-line E in advanced non-small cell lung cancer (aNSCLC): The TORCH trial.
Authors: C. Gridelli, F. Ciardiello, R. Feld, C. A. Butts, V. Gebbia, G. Genestreti, A. G. Favaretto, R. Wierzbicki, C. Gallo, F. Perrone
Journal: Journal of Clinical Oncology (2010)

7508 Background: In a placebo-controlled trial, E prolonged survival of unselected aNSCLC patients (pts) not eligible for further chemotherapy. Two phase II studies suggested that first-line treatment with E might be a valid alternative to chemotherapy. Methods: An independent non profit phase 3 trial was designed to test whether overall survival in the experimental arm, first-line E (150 mg/d po) followed at progression by CG (C 80 mg/m2 d1 + G 1,200 mg/m2 dd1&8, q3w), was not inferior than in the standard first-line CG followed at progression by E. Stage IV/IIIb (with supraclavicular nodes or pleural effusion) NSCLC pts, PS 0-1, were eligible. With a 1.25 upper limit of 95% CI of hazard ratio (HR) of death, 80% power, 0.025 1-sided alpha, a sample size of 900 pts was calculated. Secondary end-points: progression-free survival, response, toxicity, quality of life, cost-efficacy analysis, correlative studies on tumor and blood samples. Results: From Dec 06 to Nov 09, 760 pts were randomized, 380 in each arm, 612 in Italy, 148 in Canada. Baseline characteristics were balanced between arms. Median age (range) was 62 (27-81); females were 256 (33.7%); 422 (55.5%) pts had adenocarcinoma; 157 (20.6%) were never smokers; 24 (3.2%) were East-Asian. At the planned interim analysis done after 340 deaths (half of the events required for final analysis), 151 and 189 in the standard and experimental arms, HR of death in the experimental arm was 1.40 (95% CI 1.13-1.73), p = 0.002; the boundary of study interruption for inferiority was crossed. Median survival was 10.8 months in the standard and 7.7 in the experimental arm. There was no heterogeneity of the HR across gender, smoking habit, and histotype subgroups. The IDMC recommended early study termination and cross-over to CG was offered to pts receiving first- line E. Conclusions: A strategy based on first-line E followed by CG at progression is inferior than the reverse standard one, in unselected patients with aNSCLC. Data on compliance and selected secondary end-points will also be presented. Supported by Roche. Eudract #2005-005968-90; NCT00349219. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Roche Roche Roche
Clarithromycin, lenalidomide and dexamethasone combination therapy as primary treatment of multiple myeloma
Authors: R. Niesvizky, D. S. Jayabalan, J. R. Furst, H. J. Cho, R. N. Pearse, F. Zafar, R. W. Lent, J. Tepler, M. W. Schuster, J. P. Leonard, M. Coleman
Journal: Journal of Clinical Oncology (2006)

7545 Background: Lenalidomide (Revlamid [R]) is the leading clinical compound in a new group of drugs called IMiDs. Our group demonstrated that clarithromycin (Biaxin [Bi]) augments tumor mass reduction and improves responses in patients (pts) receiving low-dose thalidomide and/or dexamethasone (D). We report the results of the combination of Bi plus R plus D (BiRD) in newly diagnosed MM. Methods: A phase II trial designed to accrue 50 pts. A 2-stage design rejects a CR rate of &lt; 10% (alt &gt;30%). Between Nov. 2004 and Jan. 2006, 46 pts have been accrued of which 40 pts are eligible for evaluation. R is given po at 25 mg daily on days 1–21 of a 28-day cycle. D is given po at 40 mg once weekly. Bi is given po at 500 mg bid. Pts receive low dose aspirin (ASA)(81mg) qd as thrombosis (TE) prophylaxis. Responses are defined according to modified EBMTR criteria. Analysis is by intent-to-treat. Patient Selection: Median age: 62.5 years (36–80), Male/Female 25/15, Hgb: 10.6 g/dL (7.2–15.1), Plt 234 k/uL (51–526), β2m: 3 mg/L (0.8–12.8), CRP: 0.6 mg/dL (0.12–14.2), creat: 1.1 mg/dL (0.6–3.1), albumin 3.5 g/dL (2.3–4.9). SD stage IIIa: 48%, stage IIIb: 10% and IIa: 42%. ISS stage I: 50%, stage II: 25% and stage III: 25%. Cytogenetics and FISH: trisomy 11 (10 pts), tetrasomy 11 (3 pts), del13q14 (14 pts), t (4,14) (1pt), t (11,14) (3 pts). Results: Of the 40 evaluable pts, 38 (95%) have achieved an objective response (&gt;PR) within 3–4 months of Rx with the remaining pts continuing to respond. Seventeen pts (43%) had a &gt;90% reduction of the initial paraprotein. Nearly one third of pts have achieved either a CR (10/40) or a nCR (2/40-continuing on Rx). CR has been confirmed in all pts by normalization of free light chain levels and ratio. The remaining 26 pts (65%) achieved a PR. Of those pts who achieved a PR, 5/26 pts (19%) had &gt;90% reduction in the initial paraprotein. Nineteen pts have experienced grade ≥3 adverse events. Heme toxicities: anemia (11%), neutropenia (9%) and thrombocytopenia (9%). Non-heme toxicities (NHT) include TE in 7 patients (15%) 2 of them fatal. Four of the TE events were while off ASA. Other NHT include myopathy (6%), GI (4%), and mood (4%). Conclusions: BiRD therapy is a safe and highly effective primary therapy for symptomatic, treatment-naïve MM. [Table: see text]
Abstract 19716: Role of Aldose Reductase in Perivascular Adipose Tissue and Vascular Dysfunction in Short-Term Diet-Induced Obesity
Authors: Daniel J Conklin, Kenneth G MacKinlay, Daniel A Murphy, Petra Haberzettl, Aruni Bhatnagar
Journal: Circulation (2012)

Obesity is a risk factor for diabetes and cardiovascular (CVD) disease, and the quantity of perivascular adipose tissue (PVAT) associates with CVD risk. To test the hypothesis that changes in PVAT are causal in diet-induced vascular dysfunction, mice (wild type, WT and aldose reductase-null, ARKO, an obesity-sensitive model) were fed a low fat chow diet (10% kcal fat) or high fat chow diet (HFD; 60% kcal fat) for 4 weeks (short-term) in either 8 weeks old or 18 weeks old C57 mice (n=4-6/group). After 4 weeks, body weight and lean and fat mass was measured (DexaScan). Vascular, endothelial and PVAT function and structure were measured in isolated thoracic aorta without and with PVAT in response high potassium solution (100 mM HIK), phenylephrine (PE), acetylcholine (ACh), thromboxane A2 analog (U46619) and sodium nitroprusside (SNP). As expected, HFD increased body weight in all groups although ARKO mice (young and old) gained significantly more body weight, fat grams (whole body, epididymal), and % body fat when compared with age-matched WT mice. Similarly, aortic PVAT mass increased in ARKO mice indicating that PVAT growth mirrored visceral adiposity induced by short-term HFD feeding and enhanced in ARKO mice. PVAT significantly enhanced HIK-induced contractions and SNP-stimulated relaxations (%), decreased U46619-induced tension but neither altered PE-stimulated contraction nor ACh-induced relaxation (%) in isolated aorta of LFD-fed WT. Several of these PVAT effects were altered by age, AR deletion and 4-weeks of HFD feeding. For example, PVAT rescued endothelial dysfunction (ACh, -84.0±7.7%) detected as decreased ACh-induced relaxation in aorta without PVAT (ACh, -43.6±6.8%, p&lt;0.05) of 22-week WT mice fed HFD, indicating that short-term HFD induces compensatory PVAT changes that counteract deleterious endothelium changes -- a novel finding. Effects of PVAT were only slightly modified in ARKO mice despite a greater mass of PVAT, indicating a complicated role of AR deletion in PVAT. These data add to a growing literature that reveals a complex, integrative vascular function of PVAT that is modulated during obesity and metabolic syndrome.
The role of adjuvant chemotherapy in luminal B breast cancer.
Authors: Meng Zhao, Jianying Zhang, Janette S Laubacher, Maria-Teresa Ramirez, Charles L. Shapiro
Journal: Journal of Clinical Oncology (2014)

156 Background: Luminal B breast cancer is a heterogeneous subtype characterized by higher grade, increased proliferation rates and overall poorer prognosis. We conducted a retrospective study on the associations between adjuvant chemotherapy, HER2 overexpression, progesterone receptor (PR) and treatment outcomes. Methods: The characteristics of 1,372 patients (pts) with ER positive (ER+) breast cancer (stages 1-3) diagnosed between 1998 and 2005 were reviewed. 432 (31%) were phenotypically defined as luminal B: (2011 St. Gallen’s consensus criteria): ER+, HER2-negative (HER2-) and histological grade 3, or ER+ and HER2-positive (HER2+). ER and PR was positive if nuclear staining was &gt; 1%. HER2 was positive if IHC = 3+ or gene amplification was confirmed by FISH. Statistical analyses were performed using Kaplan-Meier estimate and multivariable cox regression. Results: Among the 432 luminal B pts, 179 cases (41%) were HER2+ and 93 (22%) were PR negative (PR-). Tumor characteristics were similar (see Table). With a median follow-up of 105 months the overall recurrence rate was 56/432 (13%) pts and the median disease-free survival (DFS) and overall survival (OS) have not been reached. No differences were observed in DFS or OS between HER2+ and HER2- groups or between PR+ and PR- groups. In multivariate analysis, Pts who received adjuvant chemotherapy had better DFS (HR = 0.3, p = 0.034) and OS (HR = 0.2, p = 0.013) and the benefit of adjuvant chemotherapy was not dependent on HER2 overexpression (DFS: HR = 1.65, p = 0.37; OS: HR = 1.65, p = 0.39) or PR status (DFS: HR = 1.8, p = 0.37; OS: HR = 2.3, p = 0.25). HER2+ in pts ≥ age of 60 (presumed postmenopausal) was associated with worse DFS (HR = 3.23, p = 0.017) and OS (HR = 3.06, p = 0.027). Conclusions: In patients with luminal B subtype adjuvant chemotherapy significantly improved OS and DFS irrelevant of HER2 or PR status. HER2+ was a poor prognostic factor in postmenopausal pts, however, the vast majority of them did not receive adjuvant trastuzumab. [Table: see text]
Toxicity evaluation of capecitabine concurrent chemoradiotherapy for stage II and III rectal cancer
Authors: J. Jin, Y. X. Li, W. H. Wang, K. Wang, Y. P. Liu, H. Fang, S. L. Wang, Z. H. Yu, Y. W. Song, Z. X. Zhou
Journal: Journal of Clinical Oncology (2008)

15067 Background: Though preoperative chemoradiotherapy is associated with improved local control and less toxicity compared with postoperative chemoradiotherapy, 5-fluorouracil based postoperative concurrent chemoradiotherapy still remains a more acceptable treatment in China. Efforts are now being focused on developing new cytotoxic agents in combination with radiotherapy (RT) to maintain the treatment results and to decrease the toxicity. A phase II study was conducted to evaluate the acute toxicity and tolerance of capecitabine combination with RT. Methods: Radiotherapy was delivered postoperatively to the total dose of DT 50Gy in 5 weeks to the pelvic region, either in 3-field technique or 3-D conformal therapy. Capecitabine was administered concurrent with RT at a dosage of 1600 mg/m2/d for 2 weeks (1st cycle) followed by a 2nd cycle after a rest of 7 days. Primary endpoint was grade 3 or 4 hematological and non-hematological toxicity. Results: Between March 2005 and December 2006, a total of 75 patients with stage II and III rectal adenocarcinoma were treated, with median age of 53 years old and 50.7% of male patients. Grade 1–3 leukopenia, diarrhea and radiation- induced dermatitis were the most common toxic side effects, which accounted for 52 (69.3%), 49 (65.3%) and 33 (44.0%) out of 75 patients, although most were within Grade 1–2. However, the grade 3 toxicity were diarrhea (24.0%, 18/75), Leukopenia (6.7%, 5/75), dermatitis (2.7%, 2/75) and fatigue (1.3%, 1/75). Hand-foot syndrome was mild, only seen in 4 patients which was grade 1. Treatment was only interrupted in 3 and 2 patients in radiotherapy and chemotherapy respectively, due to grade 3 dermatitis (n = 1), diarrhea (n = 3) and incomplete obstruction (n = 1). All patients but 9 received adjuvant chemotherapy afterwards, mainly were oxaliplatin based regimen. Up to December 1, 2007, there were 9 recurrence, including 1 local, 7 distant and 1 regional plus distant metastasis. Conclusions: In patients with stage II and III rectal adenocarcinoma treated with concurrent capecitabine chemoradiotherapy, the toxicity is well tolerated. Diarrhea is the most common and severe toxicity but with no interruption of treatment. With very close follow up, only 9 of 75 patients develop recurrence, mainly in distance. No significant financial relationships to disclose.
Prognostic significance of residual mass at the end of therapy in Group III rhabdomyosarcoma (RMS): Intergroup Rhabdomyosarcoma Study (IRS) IV experience
Authors: D. S. Hawkins, J. Stoner, S. Kao, D. Rodeberg, A. Hayes-Jordan, S. Qualman, S. Wolden, W. Meyer
Journal: Journal of Clinical Oncology (2005)

8501 Background: At the end of therapy, some patients with RMS have residual masses despite receiving all planned chemotherapy and radiotherapy. For IRS IV subjects with Group III (non-metastatic, incompletely excised at presentation) RMS, we assessed whether the presence of a residual mass at the end of therapy was associated with failure-free survival (FFS). Methods: We studied 419 Group III subjects who completed all protocol therapy without developing progressive disease. All subjects received vincristine, dactinomycin, and cyclophosphamide, +/- ifosfamide and +/- etoposide (J Clin Oncol 19:3091, 2001). Response was categorized by the best response achieved during therapy, determined by radiographic measurement of tumor. Complete response (CR: complete resolution of disease), partial response (PR: 50% decrease in the sum of the products of the maximum perpendicular diameters of measurable lesions), or no response (NR: < 50% decrease and < 25% increase) was coded by local institutions. Results: At the end of therapy, 341 (81%) of subjects achieved a best response of CR and 78 (19%) had a residual mass (best response of PR/NR). Five-year FFS was similar for subjects achieving CR (80%) compared to PR/NR (77%) (95% CI for difference: -7.5% to +13.4% for CR subjects). After adjustment for age, nodal status, primary site, and histology, the risk of failure was lower for CR subjects: RR=0.67 (95% CI: 040–1.12, p=0.13). Subjects with parameningeal (PM) primaries comprise 34% of CR and 59% of PR/NR groups, respectively. Among PM subjects, five-year FFS was similar for subjects achieving CR compared to PR/NR (CR: 115 subjects, 83%; PR/NR: 46 subjects, 74%; 95% CI: -6.3% to +23.4% for CR subjects). After adjustment for age, nodal status, and histology, the risk of failure was lower for CR subjects: RR=0.55 (95% CI: 0.26–1.16, p=0.11). Conclusion: In IRS IV, CR status at the end of protocol therapy in Group III subjects was associated with a statistically insignificant lower risk of subsequent failure. Aggressive alternative therapy is not warranted for RMS with a residual mass at the end of planned therapy. No significant financial relationships to disclose.