tbuckley/cabot-search huggingface dataset:
Sustained Phenotypic Correction of Murine Hemophilia A by In Vivo Gene Therapy
Authors: Sheila Connelly, Julie L. Andrews, Angela M. Gallo, Dawn B. Kayda, Jiahua Qian, Leon Hoyer, Michael J. Kadan, Mario I. Gorziglia, Bruce C. Trapnell, Alan McClelland, Michael Kaleko
Journal: Blood (1998)
Regorafenib (REG) in patients with hepatocellular carcinoma (HCC) progressing following sorafenib: An ongoing randomized, double-blind, phase III trial.
Authors: Ann-Lii Cheng, Richard S. Finn, Masatoshi Kudo, Josep M. Llovet, Shukui Qin, Marie-Aude Le Berre, Heiko Krissel, Jordi Bruix
Journal: Journal of Clinical Oncology (2013)

TPS4163 Background: Sorafenib is the accepted first-line systemic therapy for HCC, but no standard option is available for patients with tumor progression following sorafenib. An open-label phase II study suggested that REG, a multikinase inhibitor, had an acceptable safety profile and showed evidence of antitumor activity in patients with progressive HCC (Bolondi et al. Eur J Cancer 2011; 47 [Suppl 1]: abstract 6.576): disease control was achieved in 26/36 patients (72%) and median time to progression (TTP) was 4.3 months; median overall survival (OS) was 13.8 months. On the basis of these promising data, a phase III trial was designed. Methods: This randomized, double-blind, placebo (PBO)-controlled, multinational study (ClinicalTrials.gov identifier NCT01774344) will assess the efficacy and tolerability of REG vs PBO in patients with HCC that has progressed following sorafenib treatment (target n=530). Inclusion criteria include Barcelona Clinic Liver Cancer stage B or C disease, Child–Pugh A liver function, and Eastern Cooperative Oncology Group performance status (ECOG PS) 0 or 1. Patients who discontinued sorafenib ≥8 weeks before study entry or who received other previous systemic therapy for HCC will be excluded. Patients will be randomized in a 2:1 ratio to receive REG 160 mg or matching PBO OD for weeks 1–3 of each 4-week cycle; all patients will also receive best supportive care. Treatment will continue until disease progression, death, intolerable toxicity, or patient/investigator decision to stop. Doses of study drug may be delayed or reduced to manage clinically significant drug-related toxicities. The primary endpoint is OS; secondary endpoints are TTP, progression-free survival, tumor response, and safety. Analysis will be according to randomized group, stratified by geographic region (Asia vs rest of world), ECOG PS (0 vs 1), alfa-fetoprotein level (&lt;400 vs ≥400 ng/ml), extrahepatic disease (yes vs no), and macrovascular invasion (yes vs no). In addition, blood, plasma, and archival tissue will be assessed for pharmacokinetic and biomarker analyses, and health-related quality of life and health utility will be measured. Clinical trial information: NCT01774344.
Second-line chemotherapy with cyclophosphamide, doxorubicin and vincristine (CAV) in patients with small cell lung cancer (SCLC) initially treated with platinum and etoposide
Authors: S. Moreau, S. Labrune, M. Gozy, V. Giraud, F. Le Guillou, S. Blivet, T. Chinet
Journal: Journal of Clinical Oncology (2005)

7325 Background: SCLC is usually highly sensitive to chemotherapy but, despite a frequent dramatic initial response, most patients relapse. The purpose of this study was to evaluate the efficacy and toxicity of a second-line chemotherapy with CAV in patients with SCLC previously treated with platinum and etoposide. Methods: Eligibility criteria were: progressive disease after first-line chemotherapy with platinum and etoposide for SCLC, ECOG PS less than or equal to 2, adequate haematological, hepatic and renal function. Patients were treated with CAV every four week (cyclophosphamide: 1.5 mg/msup2, adriamycine: 70 mg/msup2, vincristine: 1.4 mg/msup2). Results: Among 58 patients who were treated with platinum and etoposide as first-line chemotherapy for SCLC in our institution between 1997 and 2002, 20 patients received a second-line chemotherapy; 17 patients fulfilled the eligibility criteria and were included in this study. Patients characteristics were: male/female: 15/2; median age: 59 years (range 47–75); limited disease/extensive disease: 6/11; chemotherapy-free interval was less than or equal to 4 months in 14 patients (82%) and > 4 months in 3 patients (7, 17 and 20 months). Efficacy: complete response was observed in 1 patient (6%), partial response in 5 patients (29%), stable disease in 0 patient and progression in 11 patients (65%). Toxicity profile: neutropenia G3–4 occurred in 7 patients (41%), anemia G3–4 in 2 patients (12%); thrombocytopenia G3–4 in 1 patient (6%), neuropathy G1–2 in 1 patient (6%). There were 3 therapy-related deaths. Median survival time was 13 months. Conclusions: CAV is effective as second-line chemotherapy in patients with SCLC initially treated with platinum and etoposide. However, its toxicity rate is high. No significant financial relationships to disclose.
Prospective randomized studies are needed to define the role of axillary lymph node dissection in primary breast cancer.
Authors: S D Costa, G von Minckwitz, J F Gauwerky, M Kaufmann, I J Diel
Journal: Journal of Clinical Oncology (1997)

Article Tools Article Tools OPTIONS & TOOLS Export Citation Track Citation Add To Favorites Rights & Permissions COMPANION ARTICLES No companion articles ARTICLE CITATION DOI: 10.1200/JCO.1997.15.8.3023 Journal of Clinical Oncology - published online before print September 21, 2016 PMID: 9256148 Prospective randomized studies are needed to define the role of axillary lymph node dissection in primary breast cancer. S D CostaxS D CostaSearch for articles by this author , G von MinckwitzxG von MinckwitzSearch for articles by this author , J F GauwerkyxJ F GauwerkySearch for articles by this author , M KaufmannxM KaufmannSearch for articles by this author , I J DielxI J DielSearch for articles by this author https://doi.org/10.1200/JCO.1997.15.8.3023 PDF "Prospective randomized studies are needed to define the role of axillary lymph node dissection in primary breast cancer.." Journal of Clinical Oncology, 15(8), pp. 3023–3024© 1997 by American Society of Clinical Oncology
Arterial Access Site and Outcomes in Patients Undergoing Percutaneous Coronary Intervention With and Without Vorapaxar
Authors: Jean-Pierre P. Dery, Kenneth Mahaffey, Pierluigi Tricoci, Harvey White, Mohua Podder, David Moliterno, Robert Harrington, Edmond Chen, John Strony, Frans Van de Werf, Khaled M. Ziada, Claes Held, Philip Aylward, Paul W. Armstrong, Sunil Rao
Journal: Circulation (2013)

Arterial Access Site and Outcomes in Patients Undergoing Percutaneous Coronary Intervention With and Without Vorapaxar
Phase I dose escalation pharmacokinetic study of erlotinib after failure of prior chemotherapy in patients with advanced NSCLC who continue to smoke
Authors: A. N. Hughes, M. O’Brien, D. Dunlop, W. Petty, E. Rankin, J. Chick, M. Conlan, P. Woll, M. Nicolson, A. Price
Journal: Journal of Clinical Oncology (2007)

3597 Background: The survival benefit associated with erlotinib is greater in never smokers than in current smokers. Former/never smokers experience a higher incidence of toxicity (e.g., rash) than current smokers, potentially due to greater erlotinib exposure. A higher dose of erlotinib, if feasible, may improve outcome in current smokers. Methods: A 2-part study was initiated to investigate the feasibility of escalating erlotinib to define the MTD in smokers and evaluate pharmacokinetics in patients (pts) dosed at this MTD versus 150 mg/d. Part I: sequential cohorts of advanced NSCLC pts currently smoking =10 cigarettes/d for = 1yr, ECOG PS 0–1, adequate organ function, and no prior EGFR inhibitor, received escalating doses of erlotinib for 14 days until DLT was seen in 2/6 pts. Part II: Upon identification of the MTD, pts were randomized between MTD and 150 mg/d erlotinib and PK assessed at D14. Pts could receive erlotinib beyond D14 until PD or toxicity. Results: Twenty-two pts were enrolled in Part I at 4 dose levels (#pts (MTD-evaluable pts)/dose level in mg/d): 3(3)/200, 6(3)/250, 8(6)/300 and 5(5)/350). Median/range age was 61 yrs (45–69) with 13 males and 9 females. Histology was Adenocarcinoma (9/22), Squamous (6/22) and other (7/22). Fourteen pts had prior RT and all had prior CT (median/range # prior regimens 1 (1–2)). Median/range # cigarettes smoked and duration of smoking was 18/d (10–40) and 42 yrs (10–54), respectively. DLT was observed in 1/6 MTD- evaluable pts at 300 mg/d (G3 rash) and 2/5 pts at 350 mg/d (G3 acneiform dermatitis and G3 fatigue/decreased ECOG PS). Otherwise treatment was well tolerated with common G1/2 toxicities limited to skin toxicity (59%), diarrhea (55%), and nausea, vomiting and metabolic or eye disorders (each 14%). Conclusions: The MTD of erlotinib in NSCLC pts who continue to smoke was 300 mg/d. Part II continues to compare the steady state PK of erlotinib at 300 versus 150 mg/d. The potential benefits of a higher dose of erlotinib in current smokers may warrant further evaluation. No significant financial relationships to disclose.
The role of surgical resection following imatinib treatment in patients with metastatic or recurrent GIST.
Authors: Baek-Yeol Ryoo, Seong Joon Park, Min-Hee Ryu, Byeong Seok Sohn, Hwa Jung Kim, Ki-Hun Kim, Sung Tae Oh, Chang Sik Yu, Jeong Hwan Yook, Byung Sik Kim, Yoon-Koo Kang
Journal: Journal of Clinical Oncology (2013)

10550 Background: Several retrospective studies have suggested that surgical resection of residual lesions could be beneficial if resection was done after disease control (partial response or stable disease) with imatinib in patients with metastatic or recurrent GIST. However, the benefit of surgical resection has not been proven yet compared to imatinib alone. Therefore, we compared the outcomes of surgical resection of residual lesions after imatinib (SI group) with those of imatinib alone (IM group) in patients with metastatic or recurrent GIST controlled with imatinib treatment. Methods: A total of 134 patients with metastatic or recurrent GIST who showed at least 6 months of disease stabilization or response to imatinib were included in this retrospective analysis. Patients were categorized into SI (n=42) or IM (n=92) group. To reduce the selection bias, propensity scores and inverse-probability-weighting (IPTW) adjustment were used in the outcome analysis. Results: Patient and tumor characteristics were statistically similar between SI and IM groups, except median age (51 in SI, 58 in IM, p=0.002), and metastases to peritoneum (12 in SI, 56 in IM, p=0.001). The patients in SI group underwent surgery of residual disease after a median 19.1 months of imatinib treatment (range, 7.2-87.0). With a median follow-up of 58.9 months (range, 15.4-129.1), progression-free survival (PFS) and overall survival (OS) were significantly longer in SI group than in IM group (PFS, 87.7 vs 42.8 months, p=0,001; OS, not reached vs 88.8 months, p=0.001). Multivariate analysis revealed SI group as well as female sex, KIT exon 11 mutation, and low initial tumor burden were associated with longer PFS, and SI group and low initial tumor burden were associated with longer OS. Even after applying IPTW adjustment, SI group showed significantly better outcome in terms of PFS (hazard ratio [HR], 2.326; 95% CI, 1.034-5.236; p=0.0412) and OS (HR, 5.464; 95% CI, 1.460-20.408; p=0.0117). Conclusions: This study strongly suggests that surgical resection of the residual lesions after disease control with imatinib may be beneficial in patients with metastatic or recurrent GIST.
Amino acid positron emission tomography to monitor chemotherapy response and predict seizure control and progression-free survival in WHO grade II gliomas
Authors: Ulrich Roelcke, Matthias T. Wyss, Martha Nowosielski, Roberta Rudà, Patrick Roth, Silvia Hofer, Norbert Galldiks, Flavio Crippa, Michael Weller, Riccardo Soffietti
Journal: Neuro-Oncology (2015)

Patients with WHO grade II glioma may respond to chemotherapy that is currently not standardized regarding timing and treatment duration. Metabolic changes during chemotherapy may precede structural tumor volume reductions. We therefore compared time courses of amino acid PET and MRI responses to temozolomide (TMZ) and assessed whether responses correlated with seizure control and progression-free survival (PFS). PET and MRI were performed before and during TMZ chemotherapy. Tumor volumes were calculated using regions-of-interest analysis. Amino acid uptake was also quantified as metabolically active tumor volume and tumor-to-cerebellum uptake ratio. One hundred twenty-five PET and 125 MRI scans from 33 patients were analyzed. Twenty-five patients showed metabolic responses that exhibited an exponential time course with a 25% reduction of the active volume on average after 2.3 months. MRI responses followed a linear course with a 25% reduction after 16.8 months. Reduction of metabolically active tumor volumes, but not reduction of PET uptake ratios or MRI tumor volumes, correlated with improved seizure control following chemotherapy (P = .012). Receiver-operating-characteristic curve analysis showed that a decrease of the active tumor volume of ≥80.5% predicts a PFS of ≥60 months (P = .018) and a decrease of ≥64.5% a PFS of ≥48 months (P = .037). Amino acid PET is superior to MRI for evaluating TMZ responses in WHO grade II glioma patients. The response delay between both imaging modalities favors amino acid PET for individually tailoring the duration of chemotherapy. Additional studies should investigate whether this personalized approach is appropriate with regard to outcome.
Patient wishes and physician inquiries regarding spiritual needs in an urban cancer center
Authors: A. B. Astrow, A. Wexler, K. Texeira, D. P. Sulmasy
Journal: Journal of Clinical Oncology (2006)

8630 Background: Prior studies have shown much interest in spirituality among patients in the rural South, but little is known about the spiritual needs and views of urban cancer patients. Methods: In Jan-Feb 2005, consecutive outpatients were asked to complete a questionnaire at the St. Vincent’s Comprehensive Cancer Center in New York City. The instrument included the QUEST satisfaction scale, demographic and clinical information, and questions about spiritual and religious beliefs and needs. Tests of association included correlation, t-tests, and χ 2 . Multivariate models were estimated using logistic techniques. Results: Of the 891 eligible patients, 81 refused, 428 cancelled their appointments or left before being approached. 13 were excluded because of incomplete questionnaires. The 369 participants had a mean age of 57.5 years; 65% were women, 67% white, 65% college-educated, 32% had breast cancer, and 67% were privately insured. Forty-seven percent were Catholic, 19% Jewish, 16% Protestant, and 6% atheist or agnostic. Sixty-six percent reported being “spiritual but not religious,” and 29% attended religious services at least once per week. Nine percent reported that staff had inquired about their spiritual or religious beliefs (0.6% by an MD), and 6% reported inquiries about their spiritual needs (0.9% by an MD). But, 82% reported that their spiritual needs were being met, and being asked about neither religious beliefs (p = .37) nor spiritual needs (p = .72) was associated with satisfaction. Still, 52% thought it appropriate for physicians to inquire about their religious beliefs and 58% thought it appropriate for physicians to inquire about their spiritual needs. Patients who described themselves as “spiritual but not religious” were less likely to think it appropriate for an MD to inquire about their religious beliefs (OR = 0.48, CI = 0.28 to 0.84), while those who attended religious services at least weekly were more likely to think it appropriate (OR = 2.86, CI = 1.45 to 5.62). Conclusions: A majority of patients thought it appropriate to be asked about their spiritual and religious beliefs and needs, but less than that reported in other settings. Few had these needs addressed by staff, especially by MDs. More religious patients were more likely to think such inquiries appropriate. No significant financial relationships to disclose.
Early response monitoring by FDG-PET to neoadjuvant chemotherapy in locally advanced breast cancer patients
Authors: C. Rousseau, L. Ferrer, B. Bridji, L. Campion, C. Sagan, M. Ricaud, I. Resche, N. Fleury, M. Campone
Journal: Journal of Clinical Oncology (2005)

2022 Background: [F18]-2-fluoro-2-deoxy-D-glucose positron emission tomography (FDG-PET) is commonly used in the diagnosis and staging of cancer. Clinical and radiological evaluation of response to neoadjuvant chemotherapy is presently based on change in tumor size, and the correlation with pathological response is often inaccurate. The aim of study is to prospectively assess FDG-PET sequential imaging as an early indicator of response to neoadjuvant chemotherapy in locally advanced breast cancer patients. Methods: A total of 250 attenuation-corrected scans has been obtained in 43 patients. Images were obtained with a CT/PET scanner (GE Discovery LS) following administration of FDG (5 MBq/kg) at the baseline and after the first, second, third and sixth course of chemotherapy. PET data were interpreted using standardized uptake value (SUV) measurements. The changes of SUV data with regard to baseline values were correlated with surgical/histopathological response. Results: Surgery and histopathology after 6 courses of chemotherapy revealed gross residual disease (GRD) in 18 patients and minimal residual disease (MDR) in 25 patients. Significant differences in FDG absolute uptake between responding and non responding patients were observed at the baseline (p<0.05) but this difference disappeared after the first course of chemotherapy. FDG uptake showed minimal change in non responding patients as documented by histopathological analysis but marked decrease up to the background level in most (19/25) responding patients. Considering a cut off value of 40% for the SUV decrease with regard to baseline, the sensitivity, specificity and accuracy for response to chemotherapy after one, two or three courses were respectively (60%, 100%, 77%), (88%, 100%, 93%), (96%, 100%, 98%). Conclusions: FDG-PET imaging of locally advanced breast cancer following two courses of neoadjuvant chemotherapy can accuratly predict pathological response to treatment. No significant financial relationships to disclose.
Early metabolic response to continuous daily dosing of sunitinib in soft tissue sarcomas (STS) other than GIST using FDG- PET
Authors: A. D. Van den Abbeele, J. T. Yap, I. Rastarhuyeva, T. Akhurst, M. L. Keohan, S. George, G. Bhuchar, J. A. Morgan, G. D. Demetri, R. G. Maki
Journal: Journal of Clinical Oncology (2008)

10529 Background: Sunitinib malate is a multitargeted tyrosine kinase inhibitor of KIT, PDGFRs, VEGFRs, FLT3, CSF-1R and RET approved for the treatment of imatinib-resistant/intolerant GIST and advanced RCC on a dosing schedule of 50 mg/day for 4 weeks followed by 2 weeks off treatment. Previous studies of sunitinib as a single agent in advanced GIST have shown early metabolic response using FDG-PET. We report the metabolic FDG-PET response of STS patients to sunitinib dosed at 37.5 mg/day in continuous 4-week cycles in a two-center phase II trial. Methods: The primary endpoint in this study, involving patients with metastatic and/or locally advanced STS other than GIST, is RECIST-defined ORR. Early metabolic response was also assessed in a subset of patients using FDG-PET/CT scanning at baseline and 10–14 days after initiation of sunitinib. For each patient, maximum standardized uptake values (SUVmax) were measured in up to 5 lesions with the greatest FDG uptake; percent change in SUVmax of individual lesions as well as summed SUVmax of all lesions per patient were calculated relative to baseline. Metabolic response was assessed using SUVmax percent-change thresholds per EORTC criteria (PR ≤ - 25% < SD < +25% ≤ PD). Results: As of Jan. 2008, 41 patients were enrolled and had received treatment. Overall efficacy and safety results are reported by Keohan et al. (ASCO 2008). One patient achieved a RECIST-defined PR, which was detected by cycle 2. FDG-PET results available for 21 patients (86 lesions) showed metabolic PR in 40 lesions, SD in 40 and PD in 6. Overall metabolic responses were 10 PR, 11 SD and 0 PD. While there were no patients with metabolic PD based on the summed SUVmax, 2 patients had 2 lesions with PD and 2 patients had 1 lesion with PD suggesting that there was heterogeneous response/progression in 4/11 patients. A detailed comparison of metabolic response and anatomic response will be presented. Conclusions: Nearly half of the patients with STS other than GIST assessed by FDG-PET achieved metabolic PR on continuous daily dosing of sunitinib 37.5 mg. Early metabolic response did not appear to correlate with RECIST-defined response. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration Infinity, Novartis, Pfizer Inc Novartis, Pfizer Inc. Infinity, Novartis, Pfizer Inc. Infinity, Novartis, Pfizer Inc.
Initial feasibility and safety results from a phase II/III clinical trial to evaluate docetaxel (D) therapy in combination with zoledronic acid (ZA) ± strontium-89 (Sr89) in hormone-refractory prostate cancer patients: ISRCTN12808747.
Authors: E. Porfiri, S. I. Collins, D. Barton, L. Billingham, D. McLaren, G. G. Nixon, J. M. Russell, C. Parker, J. Wylie, N. D. James
Journal: Journal of Clinical Oncology (2010)

4677 Background: TRAPEZE is a four-arm seamless phase II/III randomised controlled trial of 3 licensed first-line treatments given in combination to hormone refractory prostate cancer (HRPC) metastatic to bone. Patients (pts) were randomised to receive 6 cycles of D and prednisolone with either: synchronous ZA, a single dose of Sr89 day 28 post-D; both; or neither. Further D could be given at the clinician's discretion. Recruitment is ongoing to the phase III part of the trial. Methods: This analysis includes 200 pts randomized to the phase II study. Primary outcome measures were feasibility, tolerability and safety; secondary outcomes included health economic comparisons, overall and disease-free survival. Results: Median age was 65 years (range 45-82); ECOG 0: 34% 1: 55% 2: 12%; 91% pts reported some degree of pain (median McGill-Melzack score 1.6). Median follow-up was 16.7 months (mo), median survival for all pts was 13.3 mo reflecting the advanced disease at entry. 29% of patients reported at least one grade 3 or 4 adverse event (AE), the most common being haematological, with no significant difference between trial arms. Mean number of D cycles received was 5 (median 6). 139/200 (70%) pts completed 6 cycles of therapy: main reasons for non-completion were disease progression (32/200, 16%) and toxicity (21/200, 11%). 73/101 patients allocated Sr89 reached cycle 6 of chemotherapy, 2 did not receive Sr89 due to early progression post-D. There were 2 SAEs related to Sr89. The 99 pts randomised to ZA received 498/511 possible cycles during D therapy: 3 pts discontinued, only 1 due to an AE (low calcium). Post-D 60% continued ZA. Conclusions: All four treatment arms are feasible, and no safety issues were identified in relation to using docetaxel, zoledronic acid and strontium-89 in combination. The trial has now entered phase III with the objective of determining the efficacy and cost-effectiveness of each of the experimental treatment arms compared to the control arm. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration sanofi-aventis