tbuckley/cabot-search huggingface dataset:
S-1 monotherapy for the treatment of elderly patients with advanced gastric cancer
Authors: J. Lim, J. Kim, H. Yi, H. Kim, M. Lee, C. Kim
Journal: Journal of Clinical Oncology (2009)

e15671 Background: Elderly patients have often been excluded from clinical trials and only limited data are available regarding treatment of these patients. The efficacy of S-1 chemotherapy for elderly patients with advanced gastric cancer (AGC) is not well investigated. The aim of this study is to evaluate the efficacy and safety of S-1 monotherapy in elderly patients with AGC to whom conventional chemotherapy is difficult to deliver. Methods: From January 1, 2007 to August 31, 2008, a total of seventeen patients older than 70 were given S1 monotherapy. They received S-1 at a dose of 40mg/m2 BID either every 3 weeks (2 weeks on, 1 week off) or every 6 weeks (4 weeks on, 2 weeks off). Response was assessed according to RECIST criteria. Results: The patients consisted of 11 men and 6 women whose median age was 77 years (range: 71–83) with their performance status in 1 to 2. Five patients had recurrent AGC and the other 12 patients metastatic AGC at the time of diagnosis. Total 89 cycles of S-1 chemotherapy were given (median 4 cycles, range 2–12). Fifteen patients were evaluable for response because of early death in 2 patients. Response rate was 17.6% (95% Condifence Interval, 0 to 35.7); Complete remission in 0, partial remission in 3 (17.6%) and stable disease in 5 patients (29.4%). At a median follow up of 9.7 months (range: 8–11.4), median progression free survival was 5.1 months (range: 3.5–6.7) and overall survival was 9.5 months (range: 5.6–15.5). Most of the adverse effects of S1 monotherapy did not extend beyond grade 3. Grade 3 or 4 non- hematologic toxicities were not frequent and were easily manageable except in two, one of whom died of neutropenic sepsis and the other who died of subdural hemorrhage in grade 4 thrombocytopenia. Conclusions: S1 chemotherapy showed modest efficacy in elderly patients with AGC. The hematologic toxicity should be cautiously monitored in these elderly patients to avoid fatal events. Further studies are warranted for optimal management of elderly patients with metastatic or recurrent AGC. No significant financial relationships to disclose.
Combination chemotherapy with capecitabine (C), irinotecan (I), oxaliplatin (O), and bevacizumab (B; XELOXIRIA) as first-line treatment of metastatic colorectal cancer (MCRC): Preliminary results of a phase I-II trial.
Authors: S. Bazarbashi, A. H. Aljubran, H. Soudy, A. Darwish, A. Eltigani, M. Nabil-Ahmed, W. Edesa, M. Almubarak, A. Abu sabaa, M. Shoukri
Journal: Journal of Clinical Oncology (2011)

e14073 Background: FOLFOXIRI demonstrated tolerable toxicities and improved efficacy compared to FOLFIRI in MCRC in a phase III trial. Oral C has demonstrated similar efficacy to IV 5-FU and might substitute IV 5-FU in the FOLFOXIRI regimen. Methods: This is phase I-II prospective trial using fixed dosed of capecitabine (C), oxaliplatin (O), and bevacizumab (B) in combination of escalating doses of Irinotecan (I) in metastatic and locally advanced unresectable CRC patients (pts). The objectives of the study were to define the recommended dose (RD) of I in combination with C, O and B, safety and efficacy of the combination. The planned treatment in the first 3 pts was: I 150 mg/sqm over 90 min on day 1, O 130 mg/sqm over 2-h on day 1, C 2,000 mg/sqm/day from day 1 to 14, and Bevacizumab 7.5 mg/kg over 30 min on day 1. Cycles repeated every 3 weeks. I dose was increased to 200 mg/sqm or C dose was decrease to 1,300 mg/sqm/day in subsequent groups of 3 pts on the basis of the observed dose limiting toxicities (DLT). Results: Until today, 29 pts have been enrolled. We report here the results on the first 20 pts. Pts characteristic are: sex (M/F) = 12/8, PS (0/1/2) = 2/14/4, age (median/range) = 52/24-73 years, sites of disease (single/multiple) = 6/14. The DLT was G3-4 diarrhea that was observed in 2 out of 3 pts receiving I at 200 mg/sqm, The I recommended dose was 150 mg/sqm which continued as phase II trial. Grade 3-4 toxicities were: nausea and vomiting 26%, diarrhea 52%, neutropenia 16%, thrombocytopenia 5.3%, fatigue 21%. Response evaluation was done according to ITT analysis. 5 Pts were not assessable for response because of 2 or less cycles of chemotherapy (3 consent withdrawal, 2 grade 4 toxicity). One CR, and 8 PR were observed for an overall response rate of 45% (95%CI: 34-56%). Two had SD and 3 progressed. At a median follow-up of 10 months median PFS is 18.3 months and median OS was not reached. Conclusions: XELOXIRIA is toxic with diarrhea being the DLT. The recommended dose of I is 150 mg/sqm. Recruitment will continue with reduction in the C dose to 1,600 mg/sqm daily. Short follow up prohibits meaningful interpretation of efficacy.
Contributions of high resolution computed tomography on early phase of febrile neutropenia induced by chemotherapy
Authors: H. P. Faria, L. M. Arruda, C. S. Ferreira, A. L. Bastos, M. B. Silva, W. Pianna, A. J. Fenelon, W. G. Carvalho, J. Serufo
Journal: Journal of Clinical Oncology (2008)

20546 Background: This study was conducted in order to determine the prevalence of lung findings in the early phase of febrile neutropenia with normal chest radiographs (NCR) and to analyze the associate risk groups. Methods: Ethical approval and informed consent were obtained. 31 High Resolution Computed Tomographies (HRCT) were performed on 27 neutropenic patients with less than 72 hours of fever despite of empiric antibiotic treatment, from May 2006 to May 2007. All patients had NCR. The presence and distribution of focal consolidation (FC), ground-glass opacities (GGO), nodules (N), tree-in-bud pattern (TIBP) and halo sign (HS) were assessed by three radiologists. Statistical analysis of the risk factors was performed using Fisher’s exact and Mann-Whitney tests; a p value of less than 0.05 was considered statistically significant. Results: Five (16.1%) patients had respiratory symptoms, 12 (38.7%) had mucositis, 23 (74.2%) had hematological malignancy (HM). 15 patients (48.3%) had HM in complete remission, 8 (25.8%) had HM without control and 8 (25.8%) had solid tumor with or without control.11 (35%) of 31 HRCT scans demonstrated abnormalities: GGO were present in 7 (22%) patients, N in 6 (19%), FC in 4 (12%), TIBP in 2 (6%) and HS in 1 (3%) patients. Successful treatment with initial antibiotics schedule was achieved in 35.5% and no response in 9.7%. Univariant analysis identified the absence of mucositis as an independent factor of presence of pulmonary abnormalities (p=0.001). Conclusions: A high frequency of inflammatory reactions was found in neutropenic patients with less than 72 hours of fever and NCR. The incidences of pulmonary abnormalities are similar in different groups except in patients without mucositis. HRCT should be considered in the initial assessment of patients with fever and neutropenia, mainly in absence of mucositis. No significant financial relationships to disclose.
Implementation of 18F-FDG PET/CT in the management of colon cancer
Authors: P. Manente, F. Chierichetti, G. Liessi, L. Sartor, G. Vicario, S. Bissoli, S. Medea, E. Scelzi, M. Mion
Journal: Journal of Clinical Oncology (2006)

13526 Background: we began using PET in 1994 and since the beginning of 2000 we started with a PET/CT system. Aim of our study was to evaluate if PET/CT is a decision making tool in patients with a history of colon tumors. Methods: we performed PET/CT in 26 patients, 14 males and 12 females (mean age 60.9, range 42–75 years) already treated for a colon cancer. Each patient was submitted to two PET/CT scans in a period of 5–11 months. PET/CT was performed using 18F-FDG as radiopharmaceutical. In all patients other examinations were perfomed, such as liver ecography, pelvis MRI and CT scan. Results: in the first PET/CT imaging, 11/26 patients presented with normal tumor markers but suspected relapse on the basis of CI, 7/26 had increased markers but negative CI, the other 8 patients had both CI and tumor markers meaningful for recurrence. 7/26 PET/CT were normal: 5 cases with negative tumor markers but positive CI and 2 patients with increased CEA levels. Among the 19/26 positive PET/CT scans, 7 patients had normal marker levels. All positive PET/CT patients were treated and, at the second examination, progressive disease was evident in 11 out of 19. For the 7 previous negative PET/CT, the second findings showed tumor recurrence in 2 patients, but PET/CT became negative in 5 previously positive cases, submitted to surgery and/or chemotherapy. This method detected relapse in 73% of the patients and, during the follow up, it was sensitive to identify progressive disease or to prove treatment’colon cancer, based on tumoral marker assays and CI, is poorly sensitive to detect relapse. Our PET/CT data show that 37% of cases with normal marker levels have a recurrent disease. The overall results of our preliminary data lead to further considerations: 1) PET/CT gives a precise localization of lung or nodal metastases and local relapse; 2) the repeated PET/CT scan is reliable also to evaluate the effect of therapies; 3) this imaging modality may be crucial to detect relapse, but more data are needed to assess the proper time to perform PET/CT in the follow up to have a real gain in life expectancy. No significant financial relationships to disclose.
Molecular changes in epidermal growth factor receptor (EGFR) in non-small cell lung cancer (NSCLC) biopsies at time of progression compared to initial biopsy
Authors: G. Speranza, V. Cohen, J. S. Agulnik, G. Chong, F. Meilleur, G. Brandao, G. Kasymjanova, D. Small, W. H. Miller
Journal: Journal of Clinical Oncology (2009)

e22066 Background: EGFR mutations predict sensitivity and clinical outcome to tyrosine kinase inhibitors (TKI) in NSCLC. The two most commonly described mutations are Exon 19 deletion and Exon 21 L858R missense mutations. Genetic alterations over time have been described in other tumour types, but studies assessing EGFR genotypic changes with lung cancer progression are lacking. We sought to compare EGFR mutational status from lung tumors at time of recurrence or progression with the primary tumor. Methods: Using the Jewish General Hospital lung cancer database, of all patients diagnosed with NSCLC since 1999, those with biopsies at two different points in time were identified. All tumour samples were genotyped for EGFR exons 19 and 21 mutations using denaturing high performance liquid chromatography (dHPLC). Results: 29 patients were identified. Data for 12 patients, whose time of recurrence or progression varied between 4 months and 6 years, are available at this time. Of 12 patients, one had EGFR exon 19 mutation at time of diagnosis. One patient who initially displayed no EGFR mutation was found to have an exon 19 deletion at time of recurrence. The one with exon 19 at time of initial diagnosis continued to express exon 19 in the second biopsy. Conclusions: To our knowledge, this is the only study assessing changes in molecular genotype using dHPLC between primary and recurrent or progressive lung cancer biopsy specimens. Although sample size is small, it is evident that changes in EGFR mutational status can occur. Further prospective studies are required to determine how commonly molecular changes occur. No significant financial relationships to disclose.
Induction chemotherapy using paclitaxel and carboplatin and thoracic radiation prior to surgery for locoregionally advanced non-small cell lung cancer: Results of a phase II trial
Authors: J. M. Leonardo, J. F. Moran, L. Bullock, K. Sarma, N. P. Nguyen, E. Hudimac, K. Kerlin, J. Reilly, C. Philippart
Journal: Journal of Clinical Oncology (2004)

7301 Background: Surgery with complete resection of disease remains the optimal treatment for non-small cell lung cancer. We initiated a Phase II study to determine if patients with marginally resectable or potentially, but initially unresectable disease could be “downstaged” and eventually undergo a complete resection of their tumor by receiving preoperative chemotherapy and radiation. Methods: 32 patients with pathologically confirmed stage IIIA or IIIB NSCLC have been enrolled. Patients received two cycles of chemotherapy with paclitaxel (Taxol®) and carboplatin (Paraplatin®) given at 200 mg/m2 and AUC 6, respectively on days 1 and 22. An additional two cycles of paclitaxel, 175 mg/m2 and carboplatin, AUC=6 were given on days 43 and 64 concomitant with radiotherapy to a total dose of 4500cGy beginning on day 43. Patients underwent attempted resection approximately 6 weeks following completion of chemotherapy and radiation. Results: 5 of the 32 patients are still undergoing treatment. 23 of 27 patients have completed 4 cycles of chemotherapy and radiation. 20/23 underwent attempted resection. Of these, 3 were found to be unresectable at the time of surgery, and 17/20 underwent complete resection. Of the patients who had complete resection, 7/17 had a complete pathologic response with no microscopic evidence of malignancy in either the tumor or mediastinal lymph nodes. 1 of the 7 patients who had a complete pathologic response died 39 months following enrollment with carcinomatous meningitis; the remaining six patients in this group are alive without evidence of disease at 10–37 months of follow-up. Median survival for all patients enrolled in this study was 21 months. Conclusions: Neoadjuvant chemotherapy using paclitaxel and carboplatin with a limited course of thoracic radiation may markedly improve the outcome for patients with regionally advanced NSCLC who are initially unresectable. A significant number of patients who complete treatment will have a complete pathologic response. Support for this research was provided by a grant from Bristol-Myers-Squibb Oncology. Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Bristol-Myers Squibb Oncology Bristol-Myers Squibb Oncology
Preliminary results of a multicenter phase II study of imatinib and fluorourcail/leucovorin (FU/LV) in patients with unresectable or metastatic gallbladder or biliary tract cancer
Authors: K. Sprenger, M. Moehler, E. Kettner, S. El-Batran, S. Hegewisch-Becker, C. Steffens, A. Pustowka, E. Goekkurt, G. Ehninger, J. Stoehlmacher
Journal: Journal of Clinical Oncology (2009)

e15502 Background: There are no standard chemotherapeutic regimens for incurable biliary adenocarcinomas. Monotherapies with gemcitabine or FU/LV achieve occasional responses and a median overall survival of about 6 months. By blocking PDGFR a decreased intrastromal pressure may increase therapy effects of chemotherapy. The combination of imatinib and FU/LV has been shown to be safe and feasible in a previous Phase I trial. This multicenter phase II trial was designed to investigate the disease control rate (DCR) of FU/LV and imatinib. Methods: Eligibility criteria included unresectable or metastatic measurable biliary tract cancer (BTC)/gallbladder cancer (GBC), performance status &lt; 2, adequate organ function and no clinically significant cardiovascular disease. Enrolment of 44 chemonaive patients (pts.) was planned. Pts. received LV 200 mg/m2 followed by FU 2000 mg/m2 as a 24-hour infusion on days 1 and 2 combined with 600mg imatinib on days -4 to 4 (8 days). Cycles were repeated every 2 weeks up to 12 cycles. Radiological assessments were performed every 4 cycles. Results: 41 pts (19 GBC; 22 BTC) were enrolled in this phase II study since May 2007. Median age was 62 years (range 33–77), male/female=24/17, ECOG 0/1/2=13/23/5. 35 pts. showed metastatic disease at baseline. Treatment was well tolerated. Treatment related grade 3/4 toxicities included (number of pts): diarrhea (2), edema (1), neutropenia (2), nausea (2), transient SGPT elevation (4). The DCR of 26 pts. available for response assessment at time of analysis 1 was 58% (15 pts) (1 CR, 1 PR,13 SD of at least 4 cycles). 11 pts. showed progressive disease (PD) per RECIST criteria. 3 pts. had disease stabilization after 12 cycles and continue on treatment. We present these preliminary data as they represent a large patient number in this entity and response data are promising. Conclusions: This preliminary analysis suggests that the combination of FU/LV and imatinib can be safely administrated in pts. with GBC/BTC. Early evidence of antitumor activity was seen with some pts. achieving long term stabilization of the disease. [Table: see text]
FINAL EFFICACY AND SAFETY RESULTS FROM AVAglio, A PHASE III TRIAL OF BEVACIZUMAB (BEV) PLUS TEMOZOLOMIDE (TMZ) ANDRADIOTHERAPY (RT) IN NEWLY DIAGNOSED GLIOBLASTOMA
Authors: Olivier L. Chinot, Wolfgang Wick, Warren Mason, Roger Henriksson, Frank Saran, Ryo Nishikawa, Antoine F. Carpentier, Khe Hoang-Xuan, Petr Kavan, Dana Cernea, Alba A. Brandes, Magalie Hilton, Yannick Kerloeguen, Abajo Guijarro, Timothy Cloughsey
Journal: Neuro-Oncology (2013)

FINAL EFFICACY AND SAFETY RESULTS FROM AVAglio, A PHASE III TRIAL OF BEVACIZUMAB (BEV) PLUS TEMOZOLOMIDE (TMZ) ANDRADIOTHERAPY (RT) IN NEWLY DIAGNOSED GLIOBLASTOMA
Gene expression profiling of progressive and stable childhood pilocytic astrocytomas
Authors: L. Girard, J. D. Minna, T. Chen, G. Tomlinson, D. Bowers
Journal: Journal of Clinical Oncology (2004)

8546 Background: Children with Pilocytic Astrocytomas (PAs), the most common CNS tumor in childhood, may have either a quiescent or progressive clinical course. At present, extent of tumor resection and tumor location are the most important prognostic factors; biological prognostic factors are unknown. The identification of new prognostic factors for PAs may have important clinical and therapeutic implications. Methods: Ten mcg of purified mRNA was extracted from archival flash frozen tumor tissue from five completely resected recurrent PAs and six incompletely resected quiescent PAs. Samples were hybridized to the Affymetrix GeneChip arrays HG-U133A (22,283 probe sets) and HG-U133B (22,645 probe sets). The two arrays together evaluate the expression of 24,698 unique genes. Images from scanned chips were processed using Affymetrix software GCOS 1.0 to get the raw signals and p-values for each probe set. This data was then analyzed using in-house software (MATRIX): Array data were median-normalized and replicate genes were combined by averaging their signals. Samples were then grouped according to tumor recurrence or non-recurrence. Signals were averaged within each group and then compared (by calculating log ratios of recurrent vs non-recurrent PAs) and sets of genes showing differential RNA expression in the two groups were derived. Unsupervised hierarchical clustering was performed. Results: 282 genes were found to be overexpressed at least 2-fold in the subset of progressive PAs compared to the subset of quiescent PAs while 168 genes were found to be underexpressed more than 2-fold. Hierarchical clustering did not reveal any association between recurrence and global gene expression. Conclusions: These preliminary results demonstrate the ability of gene expression profiling to identify PAs with progressive clinical courses. Children with PAs with such profiling may benefit from closer monitoring and/or earlier adjuvant therapy. No significant financial relationships to disclose.
Effect of complementary alternative medical (CAM) therapy on pain and fatigue in pancreatic cancer patients
Authors: T. C. Birdsall, R. D. Levin, L. Alschuler, M. Daehler, S. M. Birdsall, J. Martin, L. Dounaevskaia, C. G. Lis, D. P. Braun
Journal: Journal of Clinical Oncology (2007)

15142 Background: Pain and fatigue are frequent, difficult to manage, and negatively impact quality of life (QOL) in pancreatic adenocarcinoma patients (PCpts) causing some to seek CAM therapy in place of or in conjunction with conventional analgesics. But the efficacy of CAM on pain and fatigue has not been adequately tested in controlled trials. We employed an alternative strategy by abstracting pain and fatigue scores from the EORTC-QLQ-C30 questionnaire administered to PCpts treated at Midwestern Regional Medical Center, an integrative oncology center offering conventional and CAM treatment. Methods: 50 PCpts treated with chemotherapy and/or radiation clinically appropriate for advanced PC + CAM were evaluated. The CAM group (n=36) had 70%, 11%, and 19% and the nonCAM group (n=14) 71%, 14%, and 15% Stage IV, III, and II tumors respectively. PCpts received narcotic and anti-inflammatory agents consistent with ASCO and NCCN guidelines. CAM treatments included Green Tea Extract; Melatonin; and high-potency multivitamins. Baseline, 3 month(M), and 6M data were analyzed. Results: Median baseline, 3M and 6M pain scores were: 50; 0; 33.3 and 75; 16.6; 83.3 for CAM and nonCAM respectively; not significant (NS) CAM vs nonCAM at any time point by non-parametric tests. Pain control at 3M was improved significantly vs baseline levels for each cohort; p=0.02 (CAM) and 0.03 (nonCAM) by paired 2 tail t tests. The relative numbers of PCpts with manageable pain (≤ 33) were comparable for CAM vs nonCAM at baseline (41% vs 36%) and 3 M (81% vs 90%), but not at 6M (67% vs 22% CAM vs nonCAM respectively, (p&lt;0.05 by ? 2 test). Median baseline, 3M and 6M fatigue scores were: 55.5; 33.3; 33.3 and 44.4; 33.3; 66.6 for CAM and nonCAM respectively (NS, CAM vs nonCAM at any time point). By paired 2-tail t tests, 3M (p=0.01) and 6M (p=0.02) values were improved significantly vs baseline in CAM but not nonCAM cohorts. Conclusion: This exploratory study shows that CAM treatment may improve fatigue and extend the period of effective pain control by conventional analgesics in PCpts. Given the negative impact exerted by pain and fatigue on QOL in this difficult to manage malignancy, CAM treatment appears to have efficacy for PCpts. No significant financial relationships to disclose.
Activity of dasatinib with chemotherapy in triple-negative breast cancer cells
Authors: D. Tryfonopoulos, N. O'Donovan, B. Corkery, M. Clynes, J. Crown
Journal: Journal of Clinical Oncology (2009)

e14605 Background: Triple-negative breast cancers (TNBC) lack expression of oestrogen, progesterone, and are HER-2 normal. TNBC cell lines have displayed greater sensitivity to growth inhibition by the multi-target kinase inhibitor, dasatinib, than luminal or HER- 2 positive breast cancer cell lines. The aim of this study was to assess the direct anti-tumor effects of dasatinib in combination with chemotherapy in TNBC. Methods: Four TNBC cell lines (MDA-MB-231, HCC-1143, HCC-1937, MDA-MB-468) were treated with dasatinib in combination with docetaxel, cisplatin or 5'-5' DFUR. IC 50 values were calculated for each drug alone by determining response in a 5-day proliferation (acid phosphatase) assay. Combination index (CI) values were determined, using CalcuSyn, to assess the interaction between drugs. Results: Three of the cell lines (MDA-MB-231, HCC- 1143, HCC-1937) were sensitive to dasatinib (IC 50 &lt; 1 μM) whereas MDA-MB-468 was resistant (IC 50 &gt; 1 μM) (Table). In MDA-MB-231 and HCC-1143 cells, combined treatment with dasatinib and 5'-5'-DFUR displayed synergy (CI&lt;1.0), whereas the combination was additive in HCC-1937 cells (CI=0.98). Combined treatment with dasatinib and cisplatin was synergistic in the three dasatinib sensitive cell lines (CI&lt;1.0). Dasatinib in combination with docetaxel displayed moderate synergy in MDA-MB-231 and HCC-1937 cells (CI&lt;1.0), but was antagonistic in HCC-1143 cells (CI&gt;1.0). Conclusions: Our findings show that the combination of dasatinib with either 5'-5'-DFUR or cisplatin is synergistic in TNBC cell lines, and suggest that combinations of dasatinib with chemotherapy may improve response in triple negative breast cancer patients. [Table: see text] No significant financial relationships to disclose.