tbuckley/cabot-search huggingface dataset:
Anemia during sequential induction chemotherapy and chemo-radiation for head and neck cancer: The impact of blood transfusion on treatment outcome
Authors: S. A. Bhide, M. Ahmed, C. Powell, K. Newbold, C. M. Nutting, K. Harrington
Journal: Journal of Clinical Oncology (2008)

6018 Purpose: Sequential treatment (C→CRT) is increasingly used for radical treatment of advanced head and neck cancer (SCCHN), but causes increased myelosuppression. Here we review the incidence of anemia and the effect of a policy of hemoglobin (Hb) maintenance by blood transfusion (BT) on disease outcomes. Methods: Chart review of patients with locally advanced SCCHN treated with C→CRT formed the basis of this study. The incidence of anemia and statistics on BT were documented. Outcomes were analysed according to: (1) Transfusion status; (2) Nadir Hb; (3) Number of transfusion episodes (NOTE); (4) Number of units of blood transfused (NOUT). Data on 3-year loco-regional control (LRC), relapse free survival (RFS), disease-specific (DSS) and overall survival (OS) were analyzed. Results: 169 patients were identified. The median follow-up was 23.6 months. The RFS (52% vs. 41%, p=0.03), DSS (71% vs. 66%, p=0.02), and OS (58% vs. 42% p=0.005) were significantly better for patients who did not require BT. The LRC, RFS, DSS and OS were also significantly better for patients with Nadir Hb level > 12 vs < 12 g/dL and NOUT 1–4 vs. >4 (Table 1). Conclusion: BT during radical treatment for SCCHN appears to be detrimental. Either patients who develop anemia have more aggressive disease or BT mediates adverse effects on treatment outcomes - possibly through increased levels of Vascular Endothelial Growth Factor (VEGF) found in transfused blood. Future clarification of the complex interactions between tissue hypoxia, anemia and correction strategies is urgently required (see Table). 3-yr Outcome (%) Transfusion status Nadir Hb (g/dL) NOTE NOUT No Yes P >12 < 12 P 0 1–2 >2 P 0 1–4 >4 P LRC 61 57 0.24 70 51 0.043 63 69 32 0.09 61 76 21 0.005 RFS 52 41 0.03 59 40 0.008 53 43 31 0.05 52 56 15 <0.001 DSS 71 66 0.02 74 61 0.05 71 59 63 0.08 71 70 42 0.002 OS 58 42 0.005 64 43 0.01 57 52 34 0.07 58 55 22 <0.001 No significant financial relationships to disclose.
A phase II trial of irinotecan, 5-fluorouracil and leucovorin in patients with previously untreated advanced colorectal cancer (CRC)
Authors: N. Lee, S. Bae, S. Lee, D. Kim, K. Kim, H. Kim, C. Kim, K. Lee, J. Won, D. Hong, H. Park
Journal: Journal of Clinical Oncology (2007)

14599 Background: We prospectively conducted a phase II trial to test the efficacy and safety of irinotecan, 5-fluorouracil and leucovorin (FOLFIRI) regimens for the first-line treatment of previously untreated patients with recurrent or metastatic advanced CRC. Methods: Thirty-four previously untreated patients with advanced CRC were enrolled in this study from June 2001 to December 2006. Eligible patients had histologically confirmed adenocarcinoma, no prior systemic therapy in palliative setting, ECOG PS = 2, adequate organ function, written informed consent and at least one measurable disease. The patients received either irinotecan 180 mg/m 2 on day 1 with a LV bolus of 200 mg/m 2 and a FU bolus of 400 mg/m 2 , and this was followed by a FU continuous infusion of 600 mg/m 2 on day 1 and day 2 (the classic FOLFIRI regimen), or they were treated with a LV bolus of 400 mg/m 2 and a FU bolus of 400 mg/m 2 followed by a FU continuous infusion of 2,400 mg/m 2 for 46 hours (the simplified FOLFIRI regimen), and these treatments were repeated every 2 weeks until disease progression. Results: There were 13 females and 21 males with median age of 54 years (range: 41–79). The most common metastatic sites were lung and liver. A total of 262 cycles were administrated with median 6 cycles per patient (range: 1–22). All pts were evaluable for toxicity, and 30 pts for response to the treatment. The objective response rate was 26.4% with 2 complete responses respectively. Sixteen (47%) pts had stable disease and 7 (20.5%) had a progression. The tumor control rate was 73.4%. The median TTP was 5.3 months, and the overall survival was 10.1 months. The prognostic factor for longer TTP and survival was the ECOG performance status (PS). The type of regimens was not affected on response rate, TTP and survival. The chemotherapy was generally well tolerated and the most common grade 3–4 toxicities were neutropenia, diarrhea. The non- hematological toxicities were similar for both treatment groups, with more frequent grade =3 neutropenia being noted for the simplified FOLFIRI regimen. Conclusions: The FOLFIRI regimen was demonstrated to have a moderate antitumor activity with acceptable toxicity profiles, and tend to show more favorable outcome for patients with good ECOG PS. No significant financial relationships to disclose.
Endoscopic ultrasound downstage after neoadjuvant chemotherpy predicts survival of locally advanced esophageal cancer
Authors: A. Ribeiro, A. Livingstone, D. Franceschi, S. Richman, M. Lima, J. Parra, K. Hamilton, B. Ardalan
Journal: Journal of Clinical Oncology (2005)

4196 Background: Endoscopic ultrasound (EUS) plays a central role in the initial staging and treatment of esophageal cancer (EC). Use of EUS for re-staging patients (pts) after neoadjuvant therapy is controversial. Few studies have suggested that EUS post-neoadjuvant therapy can accurately predict tumor response and overall survival in pts with locally advanced disease. Methods: EUS data from an ongoing study on neoadjuvant chemotherapy for locally advanced EC with Paclitaxel 125 mg/m2, Fluorodeoxyuridine 150 m/Kg or 80 mg/Kg, Leucovorin 500 mg/m2 and Cisplatin 100 mg/ m2 was collected. EUS performed pre- and post-chemotherapy in all pts. Maximum tumor thickness was measured on EUS pre- and post-chemotherapy and EUS stage compared to surgical pathology (AJCC TNM stage). More than 50% wall thickness reduction was classified as a response by EUS. Results: 38 pts were included, mean age 62 yrs. There were 35 adenocarcinomas of the gastroesophageal junction and three squamous cell carcinomas. The median follow-up time among 26 pts still alive was 19 months (range: 3–75 months). The 1-, 3- and 5-yrs overall survival was respectively: 88%, 63% and 45%. The 1- and 3-yrs survival of pts who had more than 50% reduction in tumor thickness after chemotherapy was superior to those with less than 50%: 1yr survival:92% vs. 85% and 3-yrs: 70% vs. 59% (p=0.39 Log-rank test). On EUS post- chemotherapy, patients who had either T or N downstage had better survival than those without downstage; 3-yrs survival: 88% vs. 40% respectively; p=0.004. Presence of N1 disease on surgical pathology was associated with worse 1- and 3-yrs survival: N0 disease (94% and 83%) vs. N1 disease (7% and 47%) (Log-rank test, p= 0.012). Conclusions: Patients with tumor response (>50% reduction of wall thickness) to neoadjuvant chemotherapy verified by EUS appears to have an improved survival but it did not reach statistical significance in our study at this point. Tumor downstaging after neoadjuvant chemotherapy verified by EUS and absence of nodes on pathological staging are associated with improved survival. The role of EUS appears promising in predicting patient’s survival based on tumor response after neoadjuvant chemotherapy. No significant financial relationships to disclose.
Primary prophylaxis with 3 weekly pegfilgrastim and ciprofloxacin effectively prevent (febrile) neutropenia and infection during neoadjuvant chemotherapy with docetaxel/doxorubicin/cyclophosphamide (TAC) in breast cancer patients
Authors: G. von Minckwitz, J. U. Blohmer, A. Löhr, G. Raab, H. Eidtmann, B. Gerber, J. Hilfrich, J. Huober, S. D. Costa, C. Jackisch, M. Kaufmann
Journal: Journal of Clinical Oncology (2005)

8008 Background: Neutropenia and infections are frequently related with the administration of TAC (docetaxel 75mg/m2, doxorubicin 50 mg/m2, cyclophosphamide 500 mg/m2 day 1, q21). We assessed in three prospective consecutive cohorts (N=949 patients) if the frequencies of (febrile) neutropenia and infections could be reduced using a primary prophylaxis with pegfilgrastim (+/- ciprofloxacin) compared to filgrastim. Methods: The GEPARTRIO-study, a phase III trial on the use of 6 to 8 cycles of TAC as neoadjuvant treatment in T2-T4 stage primary breast cancer has started using a primary prophylaxis with filgrastim given s.c. on day 3–12 every cycle in 390 patients (2401 cycles) (cohort A), pegfilgrastim given s.c. only on day 2 after amendment 1 in 323 patients (1956 cycles) (cohort B) and pegfilgrastim together with ciprofloxacin 500 mg bid on days 5–14 after amendment 2 in 236 patients (1111 cycles) (cohort C). Results: Neutropenia (maximum toxicity per patients) all grades (grades III/IV) was observed in 81.9 (65.6)% (A), 63.7 (45.0)% (B) and 59.6(42.2)% (C) (p<0.001, A vs B+C, Chi2-test). Febrile neutropenia was reported in 17.1% (A) 6.4% (B) and 4.3% (C) (p<0.001, A vs B vs C). Fever without neutropenia was observed in 16.7% (A), 15.1% (B) and 8.9% (C) (p<0.01, A+B vs C). Infections (all grades) were diagnosed in 31.2% (A), 27.8% (B) and 23.0% (C) (p<0.05, A+B vs C). Conclusions: (Febrile)neutropenia and infections during neoadjuvant chemotherapy with TAC can most effectively be avoided by primary prophylaxis with pegfilgrastim in combination with ciprofloxacin. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Amgen
The incidence of low-level HER2 gene amplification and chromosome 17 polysomy in cases of newly diagnosed breast cancer and their association with clinical prognostic markers
Authors: J. R. Diamond, R. Amaria, C. I. O'Donnell, L. Meltesen, K. Swisshelm, D. Melancon, L. McGavran, M. Singh, A. Elias, V. F. Borges
Journal: Journal of Clinical Oncology (2009)

e22012 Background: The purpose of this study is to describe the frequency of low level HER2 gene amplification and chromosome 17 polysomy, and its association with known clinical prognostic markers. Methods: We retrospectively reviewed all cases of newly diagnosed invasive breast cancer referred to the Colorado Cytogenetic laboratory for FISH testing from either the University of Colorado Breast Center or St. Mary's Hospital in Grand Junction, CO between October 2000 and May 2005, excluding patients treated with HER2-directed therapy. Cases were classified into positive for HER2 gene amplification (FISH ratio ≥ 2.2), negative for HER2 gene amplification (FISH ratio &lt;1.8), or intermediate for HER2 gene amplification (FISH ratio of 1.8- 2.1 or presence of chromosome 17 polysomy). IRB approved chart review was performed . Results: Of the 177 patients referred for FISH testing during the study period, 27.7 % (49/177) had intermediate HER2 gene amplification as defined as a FISH ratio of 1.8–2.1 or chromosome 17 polysomy. There was a statistically significant increase in stage, lymph node involvement, and histologic grade at diagnosis in the intermediate HER2 group compared to negative controls ( Table ). Conclusions: The incidence of intermediate HER2 gene amplification is clinically significant and associated with higher histologic grade and stage at diagnosis compared to HER2 negative controls. This patient population should be investigated further for long term disease outcomes and impact of HER2 - based targeted therapy. [Table: see text] No significant financial relationships to disclose.
Phase II study of temozolomide (TMZ) in metastatic colorectal cancer (mCRC) patients molecularly selected by MGMT promoter hypermethylation.
Authors: Alessio Amatu, Katia Bencardino, Ludovic Barault, Andrea Cassingena, Erica Bonazzina, Silvia Ghezzi, Catia Moutinho, Federica Tosi, Riccardo Ricotta, Elena Magni, Rosalinda Gatto, Giovanna Marrapese, Manel Esteller, Alberto Bardelli, Federica Di Nicolantonio, Andrea Sartore-Bianchi, Salvatore Siena
Journal: Journal of Clinical Oncology (2015)

583 Background: O(6)-methylguanine-DNA-methyltransferase (MGMT) is a DNA repair protein. About 40% of mCRC display MGMT deficiency due to promoter hypermethylation, leading to susceptibility to treatment with cytotoxic alkylating agents. We previously reported that objective clinical response to dacarbazine is confined to tumors harboring MGMT promoter hypermethylation (Amatu et al. Clin Cancer Res 2013). Based on these findings, we conducted a phase II study with TMZ in MGMT-deficient mCRCs after failure of standard therapies (EudraCT 2012-003338-17). Methods: We screened mCRC patients for MGMT promoter hypermethylation on archival FFPE specimens by methylation-specific PCR (MSP). All eligible patients underwent tumor biopsy prior to start of treatment. Patients received TMZ 200 mg/m 2 po qd days 1-5 q28 until progression or intolerable toxicity. We used a Fleming single-stage design to determine whether PFS rate at 12 week would be ≥35% (H 0 ≤15%, type I error=0.059 (1-sided) and power=0.849). Secondary endpoints included response rate (RR), disease control rate (DCR), overall survival (OS), and association of clinical outcomes with quantitative MGMT evaluation in serum and fresh tissue. Results: 150 patients were screened: 54 (36%) presented MGMT promoter hypermethylation and 29 were eligible and enrolled from December 2012 to May 2014 (M 69%, median age 60y [38-77], mean number of previous treatment lines 5.6). A median of 2 cycles of TMZ were administered (range 1-5). Primary endpoint was not achieved, since PFS rate at 12 weeks was 10.3% (90% CI: 2.9-24.6). DCR was 48.3% (90% CI: 32.0-64.8), median OS 6.2 months (95% CI: 3.7-7.6), and median PFS 2.6 months (95% CI: 1.4-2.7). G3/4 toxicities occurring in ≥10% of patients included: thrombocytopenia (10.3/13.8%), neutropenia (0/10.3%) and increased bilirubin (11.1/0%). Exploratory MGMT quantitative analysis is in progress. Conclusions: In mCRC patients treated with TMZ, selection according to MGMT promoter hypermethylation by MSP did not provide meaningful PFS rate at 12 weeks. Biomarkers analyses on serum and fresh tumor biopsy are ongoing to identify the subgroup of mCRCs benefiting from treatment. Clinical trial information: 2012-003338-17.
Overcoming resistance to EGFR inhibitors in NSCLC cell lines by sequential treatment with histone deacetylase inhibitors
Authors: S. E. Witta, B. Helfrich, D. Chan, F. Hirsch, W. Franklin, H. A. Drabkin, R. M. Gemmill, P. A. Bunn
Journal: Journal of Clinical Oncology (2005)

7083 Background: The epidermal growth factor receptor (EGFR) is overexpressed in the majority of non-small cell lung cancers (NSCLC). EGFR inhibitors, such as gefitinib and erlotinib produce 11–20% response rates in NSCLC patients. E-cadherin, a cell adhesion molecule, regulates the phosphorylation of EGFR. NSCLC cell lines were used as a model to identify molecules that predict response to EGFR inhibitors and to develop strategies that enhance the effect of EGFR inhibitors. Methods: Cell proliferation: cell lines were incubated in the presence of various gefitinib concentrations and cell growth was assessed with MTT assay. Apoptosis: Cell death was assessed using the vibrant apoptosis assay and evaluated with flow cytometry. Samples were assessed in the presence or absence of gefitinib or HDAC inhibitors. Results: Using real time RT-PCR and western blotting, E-cadhein was expressed in cell lines sensitive to gefitinib, including those with EGFR mutation and gene amplification. None of the gefitinib-resistant cell lines expressed E-cadherin. Overexpression of E-cadherin in the gefitinib-resistant cell line, H157, led to increased sensitivity to gefitinib. E-cadherin expression is inhibited by the zinc finger repressor, ZEB-1, with the recruitment of histone deacetylases. ZEB1 was expressed in gefitinib resistant cell lines while expression was lacking in gefitinib sensitive ones. Inhibiting histone deacetylase enhanced response to gefitinib in all the resistant cell lines tested. There was 20 to 50 fold higher induction of apoptosis and cell death when cells were pretreated with HDAC inhibitors 24 hours prior to gefitinib. Conclusions: These studies indicate that expression of E-cadherin may predict response to gefitinib. Pretreatment with HDAC inhibitors augments response to EGFR inhibitors in NSCLC cells. Phase I/II clinical trials will be designed based on this sequential treatment of HDAC and EGFR inhibitors. No significant financial relationships to disclose.
Abstract 16571: Echocardiographic Predictors of Outcomes Add Value to the Seattle Heart Failure Model in Patients Referred for LVAD and/or Transplant Evaluation
Authors: Jerry D Estep, Andrea M Cordero-Reyes, Rey P Vivo, Luis J Garcia-Morales, Mazen Barbandi, Sireesha Garikipati, Selim R Krim, Arvind Bhimaraj, Wayne C Levy, Guillermo Torre-Amione
Journal: Circulation (2012)

Introduction and objectives: Patients with advanced heart failure are commonly evaluated based on a series of demographic, functional and clinical parameters. The modified Seattle Heart Failure Mod...
A phase I study of everolimus plus sorafenib in patients with metastatic renal cell carcinoma (mRCC)
Authors: P. Cen, A. Daleiden, G. Doshi, R. Amato
Journal: Journal of Clinical Oncology (2009)

e16056 Background: Everolimus, a mTOR inhibitor and Sorafenib, a Raf kinase inhibitor had shown their efficacy in RCC, as single agents. Combining these two active agents could have potential additive or synergistic effects. We conducted a phase I study to evaluate the maximum tolerated dose (MTD) of this combination in patients with progressive mRCC. Methods: Patients predominantly had clear cell RCC, and progressive measurable diseases on prior treatments including immunotherapy, TKI and/or Everolimus. Patients were evaluated weekly for toxicities and every 8 weeks for radiological response, including at least both PET/CT and CT scans at baseline and 1 st staging. Patients received daily Everolimus and twice daily sorafenib both orally at escalating dose levels of 2.5mg/400mg (dose level 0), 5mg/400mg (+1), and 10mg/400mg (+2). Results: 18 patients with mRCC were enrolled and 15 patients were evaluable. 6 patients were treated on dose level 0, dose- limited toxicity (DLT) was found in 2/6 patients, one with thrombocytopenia/leukopenia, the other with pneumonitis; 6 patients were treated on dose level +1, DLT of pulmonary embolism was found in 1/6 patient; and 3 patients were treated on dose level +2, without DLT. The most common side effect was grade 1/2 hand-foot syndrome (4/15, 27%). The MTD was dose level +2. Overall response by RECIST was 27% (4/15 patients): pathological complete response (CR) was 6% (1/15); radiographic CR was 6% (1/5); surgical CR after resection was 6% (1/15). 47% (7/15) of the patients had stable disease. Decreased FDG uptake was found in 67% (10/15) of the patients. The median PFS was 5.53 months (range, 1.4–14.7), and OS was 7.9 months (range, 2.3–23). Conclusions: The MTD of combining daily Everolimus 10mg and twice daily sorafenib 400mg are safe and effective for progressive metastatic RCC. The phase II trial is planned to start in early 2009. [Table: see text]
A nomogram for predicting serious complications in patients with solid tumors and apparently stable febrile neutropenia: Prospective data on 781 consecutive episodes from the FINITE study.
Authors: Ismael Ghanem, Maite Antonio Rebollo, Marcelo Garrido, Jeronimo Martinez, Carme Font, Avinash Ramchandani, Merce Biosca, Carmen Beato, Eva Martinez de Castro, Eduardo Castanon, Juan Virizuela Echaburu, Javier Espinosa, Elena Sevillano, Isabel Aragon Manrique, Merce Cardona, Rebeca Mondejar, Francisco Baron, Francisco Acevedo, Paula Jiménez-Fonseca, Alberto Carmona Bayonas
Journal: Journal of Clinical Oncology (2014)

165 Background: An accurate estimate of the likelihood of serious complications in patients with otherwise apparently stable febrile neutropenia (FN) may assist in decision-making regarding individualized therapy. Our group has developed a prognostic score for predicting complications in patients with solid tumors and apparently stable episodes called CISNE (Clinical Index for Stable Febrile Neutropenia). The purpose of this study is to present a nomogram based on the previously mentioned index in a broader dataset of patients. Methods: FINITE is a prospective and multicenter study which aims to investigate prognostic factors and outcomes of FN episodes with clinical stability at first assessment, defined as events without acute organ dysfunction, vital signs abnormalities or major infections. We performed a nomogram based on the CISNE score which includes the following prognostic variables: ECOG PS≥2, chronic obstructive pulmonary disease, cardiovascular disease, mucositis NCI grade ≥2, monocytes &lt;200/mm3 and stress-induced hyperglycemia. A calibration plot was used to analyze the accuracy of this multivariate nomogram. Results: From October 2012 to December 2013, 781 patients with apparently stable FN were recruited in 21 Spanish hospitals. The rate of infection-related complications and death was 15.6% (95% confidence interval [CI], 12.9-18.6%) and 1.7% (95% CI, 0.98%-3.01%). A nomogram was designed according to the CISNE score. The area under the ROC curve was 0.836 (95% CI, 0.808-0.861). The observed and predicted probabilities also matched closely. Conclusions: Our group has developed a user-friendly nomogram for predicting complications in patients with apparently stable FN. This nomogram may be particularly useful to prevent premature discharges of cancer patients starting inpatient management.
A randomized comparison of carboplatin/vinorelbine versus carboplatin/gemcitabine in advanced non-small cell lung cancer (NSCLC)
Authors: N. Helbekkmo, S. H. Sundtroem, U. Aaseboe, P. F. Brunsvig, C. L. Von Plessen, R. M. Bremnes
Journal: Journal of Clinical Oncology (2006)

7033 Background: Carboplatin/vinorelbine (CV) and carboplatin/gemcitabine (CG) are novel 2-drug combinations in the treatment of NSCLC. In a randomized national multicenter phase III study in stage IIIB and IV patients (pts), we compared these regimens with respect to efficacy, toxicity and quality of life (QoL). Methods: Chemonaive pts with histologically or cytologically proven NSCLC, stage IIIB or IV and ECOG performance status (PS) 0–2 were eligible. There was no upper age limit. Pts received vinorelbine 25 mg/m 2 or gemcitabine 1000 mg/m 2 , both administered on day 1 and 8, in combination with carboplatin (Chatelut AUC 4) at day 1. Three courses were administered in 3-week cycles. QoL questionnaires were completed at baseline, before each cycle and then every 8 weeks up to one year. Primary endpoints were survival and QoL and secondary endpoints toxicity and time to progression (TTP). Stratification was done for age, stage and PS, and the planned sample size per arm was minimum 200. The analyses were performed on an intention-to-treat basis Results: From Oct 2003 through Dec 2004, 433 pts from 33 institutions were randomized to CV (n=218) or CG (n=215). Follow-up was minimum one year. There was no difference in overall survival between the two arms (p=0.89). Median survival was 7.3 vs. 6.5 months and 1-year survival 28% and 31% in the CV and CG arm respectively. TTP was significantly longer in the CG arm (p=0.006) with median TTP 4.2 vs. 3.9 months. There was significantly more grade 3–4 anemia and thrombocytopenia in the CG arm (p&lt;0.001) and more grade 3–4 leucopenia in the CV arm (p= 0.001). More pts in the CG arm needed transfusions of blood (p=0.003) or platelets (p=0.001). There was no difference between the arms with respect to neutropenic infections (p=0.87). QoL data are still being analyzed and will be presented at ASCO. Conclusions: Overall survival was similar in the two treatment arms. In the CG arm, the median TTP was longer, but grade 3–4 toxicity requiring interventions, was more frequent when compared to the VC arm. No significant financial relationships to disclose.