tbuckley/cabot-search huggingface dataset:
A randomized phase III study comparing gemcitabine + pemetrexed versus gemcitabine in patients with locally advanced and metastatic pancreas cancer
Authors: D. A. Richards, H. L. Kindler, H. Oettle, R. K. Ramanathan, J.-L. Van Laethem, M. Peeters, M. Fuchs, W. John, M. Arning, D. Von Hoff
Journal: Journal of Clinical Oncology (2004)

4007 Background: Pemetrexed (P) (ALIMTA) is a multitargeted antifolate with broad antitumor activity in solid tumors, including pancreas cancer (PC). Gemcitabine (G) (GEMZAR) is the current standard of care for inoperable PC. The combination of G and P has shown preclinical synergy and activity in a phase II study in PC [Kindler et al., ASCO 2002]. Methods: This study compared G 1250 mg/m2 day (d)1 & d 8 and P 500 mg/m2 d 8 q 3 weeks to G 1000 mg/m2 d 1, 8, 15 q 4 weeks in chemonaive patients (pts). Primary objective was overall survival (OS); secondary objectives were progression-free survival (PFS), time to progressive disease (TTP), response rate (RR), quality of life (QoL), and toxicity. Pts were stratified for performance status, disease stage, baseline homocysteine levels and investigational centers. Results: 565 pts (GP 283; G 282) were randomized. Baseline characteristics were well balanced (GP/G) with median age (63/63), stage IV disease (90%/91%), ECOG PS 0–1 (85%/88%), and liver metastasis (63%/63%). Median treatment duration was 12 weeks in both arms. There was no statistical difference in OS (p=0.848; censoring rate 16.3%; median 6.2 months (m) for GP and 6.3 m for G). RR was significantly better (p=0.006) for GP (18.3%; 42/230) than G (9.1%,20/220) as was median TTP (5.2 m for GP vs 3.6 m, p=0.042). PFS (3.9 m vs 3.3 m; p=0.11) and 1-year survival (21.4 vs 20.1%; p=0.718) were similar in both arms. Second-line therapy was given to 39% of the pts (PG 34%; G 43%). Of the planned doses, 75.3% of G and 86.9% of P in the GP arm were given, 86.5% in the G arm. Weekly mean dose of G was similar in both arms (628 vs 610 mg/m2). There were 3 treatment-related deaths in the PG arm. More grade 3/4 toxicity was seen for PG: neutropenia (45.1% vs 12.8%), thrombocytopenia (17.9% v 6.2%), anemia (13.9% v. 2.9%), febrile neutropenia (9.9% vs 0.4%), all differences p<0.001, and fatigue (15% vs 6.6%, p<0.05). Otherwise, both treatments were well tolerated. Overall QoL was well preserved in both treatment arms. Conclusions: PG improved TTP and RR, but not survival. Gemcitabine monotherapy remains the global standard of care for inoperable PC. Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Eli Lilly and Company Eli Lilly and Company Eli Lilly and Company Eli Lilly and Company Eli Lilly and Company
Treatment of EBV-associated T cell post-transplant lymphoproliferative disorder with CNS involvement in a pediatric solid-organ transplant patient
Authors: P. D. Harker-Murray, V. Dayton, J. Neglia, J. Tolar
Journal: Journal of Clinical Oncology (2006)

9040 Background: Post-transplant lymphoproliferative disorder (PTLD) is a known complication of immunosuppression following solid organ and stem cell transplantation. It ranges from benign lymphoid hyperplasia to fulminant systemic disease with high mortality. Most cases are B lineage and associated with Epstein-Barr virus (EBV + ). T cell PTLD is rare and usually EBV negative. To date only 5 cases of EBV + T cell PTLD have been reported in pediatric patients and none have had documented involvement of the central nervous system (CNS). Methods: We provide clinical, histologic, immunophenotypic and molecular details of a case of fulminant EBV + T cell PTLD with CNS involvement and compare our data to the clinical presentations, biology and outcomes of the other reported cases of pediatric T cell PTLD (these include 5 EBV + CNS − cases, 3 EBV − CNS + cases, and 4 EBV − CNS − cases with dissemination or marrow involvement). Results: A 4.5 year old male developed EBV + T cell PTLD with CNS involvement 3 years following a cadaveric renal transplantation. His fulminant presentation included fever, hypotension, splenomegaly, pancytopenia, coagulopathy, and bilateral pleural effusions. He had lymphocytosis in his CSF and his MRI showed brain white matter changes consistent with leukoencephalopathy. T lineage was confirmed by the presence of T cell markers CD3, 5, 7, 45 and TCRγ. The presence of EBV was demonstrated by in situ hybridization for EBER. His treatment followed the Children’s Oncology Group protocol A5971 for disseminated lymphoblastic lymphoma that employs a standard NHL/BFM-95 regimen with cyclophosphamide and anthracycline intensification during the induction and delayed intensification phases with a treatment duration of 2 years. He has received no irradiation. After 16 months, he has no measurable disease. Conclusions: EBV + T cell PTLD is extremely rare in pediatrics and has resulted in mortality in 12 of 17 reported cases. This is the first report of EBV + T cell PTLD with CNS involvement in a pediatric patient. Although no standardized treatment exists, the fulminant presentation, T lineage disease, and CNS involvement warranted aggressive systemic and intrathecal chemotherapy. No significant financial relationships to disclose.
OGX-427, a 2'methoxyethyl antisense oligonucleotide (ASO), against HSP27: Results of a first-in-human trial
Authors: S. J. Hotte, E. Y. Yu, H. W. Hirte, C. S. Higano, M. Gleave, K. N. Chi
Journal: Journal of Clinical Oncology (2009)

3506 Background: Heat shock protein 27 (Hsp27) is a chaperone protein expressed in many cancers and implicated as a therapeutic “hyper-node” affecting multiple pathways in cancer progression. Overexpression of Hsp27 confers a resistant phenotype. OGX-427 is a second generation ASO that inhibits Hsp27 expression which in preclinical models inhibited cell growth, induced apoptosis, and enhanced chemotherapy efficacy. The purpose of this phase 1 study was to determine the recommended phase 2 dose of OGX-427 alone and in combination with docetaxel. Methods: Eligible patients (pts) had to have metastatic breast, ovarian, prostate, NSCLC, or bladder cancer. OGX-427 was administered IV weekly on a 21-day cycle after 3 loading doses (LD) within 9 days. OGX-427 was escalated over 5 planned dose levels (DL) (200, 400, 600, 800, 1,000 mg), with 6 pts/DL. Plasma PK and serial ECGs were performed in cycle 1. Circulating tumor cells (CTC), Hsp27+ CTC and serum Hsp27 levels were evaluated serially. Results: 34 pts have been accrued and single agent dose escalation is complete. Median age was 62 (range: 33–86) yrs; 16 pts had prostate, 10 breast, 5 ovary and 3 lung ca. Median cycles administered were 2 (0–8) with 2 pts remaining on treatment. Most common related AEs: chills (53%), pruritis (29%), flushing (21%), elevated creatinine (18%), fatigue (15%), arthralgia (15%). More than 80% of pts had grade (Gr) 1/2 infusion reactions during the LDs or C1. One pt on 1,000 mg DL was hospitalized with Gr 3 infusion reaction. Gr 3 elevations of PTT (with normal INR) were seen in &gt;50% of pts on 800 and 1,000 mg DL. At 600 mg DL, one pt had a Gr 3 epistaxis and one pt had a DLT with a Gr 3 cerebral bleed into a metastasis. No significant QTcF changes were observed. Three pts with prostate ca had PSA declines of 43%, 58%, 62% and 3 pts with ovarian cancer had CA-125 declines of 27%, 28%, and 41%. Five pts have had stable disease for &gt;3 months. Preliminary mean PK data for 200–600 mg DLs: T 1/2 = 2.8–3.1 hrs, peak concentration = 21,756 - 102,591 ng/mL and AUC inf ranged from 63,552 - 328,153 ng.h/mL, increasing with dose. Declines in CTC and Hsp27+ CTC have been observed at all DL. Conclusions: OGX-427 was well tolerated. Toxicity consisted mainly of infusion reactions and transient PTT changes. Changes in tumor markers suggest single-agent activity. [Table: see text]
M30 and M65 assessments demonstrate pro-apoptotic effect of LBY135, a monoclonal antibody agonist to DR5
Authors: V. Modur, M. Motwani, J. W. Scott, L. Krajkovich, J. R. Infante, H. A. Burris, S. Sharma, M. Goldbrunner, J. C. Barrett, J. A. Gietema
Journal: Journal of Clinical Oncology (2008)

14587 Background: LBY135 is a chimeric (mouse/human) IgG1 monoclonal antibody agonist that binds with high specificity to the DR5 receptor and mimics the action of TRAIL. In a phase I trial, LBY135 has been administered once every 21-days to adult patients (pts) with advanced solid tumors at dose levels of: 0.3, 1, 3, 10, 15, 20 and 40 mg/kg. In this trial, M30 and M65 assessments, that measure cleaved and total cytokeratin 18 as indicators of cell death, were performed to determine the effect of LBY135 on tumor. Methods: Using validated ELISA assays, M30 and M65 analysis were performed on serum obtained at baseline, and 8 hours (hrs), 24 hrs, 72 hrs, 8 days and 21 days after LBY135 administration. Results: A total of 29 pts were assessed in cycles 1 and 2 of LBY135 administration across dose groups. The intra-individual variability of M30 and M65 was calculated to be < 50% by determining the spread between samples obtained at baseline and at 8 hours after first LBY135 administration in 22 pts in whom the two samples were taken between 2 and 35 days apart. At baseline, 10/29 patients (34%) were found to have levels of M30 and M65 within the same range as those of normal blood donors; while 19/29 pts (66%) had levels >3 standard deviations above the mean for normal blood donors. In these 19 patients, in whom M30 and M65 elevations at baseline suggest a likelihood of signal from tumor, 10 pts had elevations of M30 and M65 of > 50% on at least two occasions after LBY135 administration. In contrast, only 1 of 10 pts with baseline M30 and M65 levels within normal range had elevations of > 50% on two or more occasions after LBY135 administration. No correlations between dose levels and induction of M30 and M65 increases were seen. One patient with mesothelioma treated at 0.3 mg/kg dose level for greater than 20 cycles had elevations of M30 and M65 coinciding with LBY135 administration for 16 cycles. Conclusions: Changes in M30 and M65 levels in response to LBY135 suggest treatment effect, but direct correlations with dose and clinical response are difficult due to a potential complex interaction of tumor susceptibility and baseline tumor CK18 expression that determine levels of tumor apoptosis and the subsequent release of CK18 in the circulation. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration Novartis Novartis Novartis Novartis
Daily concurrent chemoradiotherapy with docetaxel (DOC) and cisplatin (CDDP) using superselective intra-arterial infusion via superficial temporal artery for T3 and T4 head and neck cancer: Possibility of organ preservation in advanced head and neck cancer
Authors: K. Mitsudo, T. Shigetomi, H. Nishiguchi, T. Fukui, N. Yamamoto, H. Furue, M. Ueda, Y. Ohhara, T. Iwai, I. Tohnai
Journal: Journal of Clinical Oncology (2009)

e17020 Background: Superselective intra-arterial chemotherapy via a superficial temporal artery (HFT method) has become feasible for daily concurrent radiotherapy and chemotherapy for head and neck cancer. We used this novel method for head and neck cancer, and evaluated its efficacy. Treatment consisted of superselective intra-arterial infusions (docetaxel total 60 mg/m 2 , cisplatin total 100 mg/m 2 ) and concurrent radiotherapy (total 40 Gy) for 4 weeks as preoperative therapy. Thirty-five patients with stage III and IV oral cancer underwent surgery after this treatment, of whom pathological complete response (CR) was obtained in 31 (88.6%). In this study, the possibility of organ preservation in cases of advanced head and neck cancer was evaluated based on this result. Methods: Eligibility included T3 or T4 squamous cell carcinoma of head and neck. Treatment consisted of superselective intra-arterial infusions (docetaxel, total 60 mg/m 2 , cisplatin, total 150 mg/m 2 ) and concurrent radiotherapy (total 60 Gy) for 6 weeks. Organ preservation was demonstrated in cases when the biopsy specimen of the primary lesion showed grade 3 (non-viable tumor cells present) or grade 4 (no tumor cells present) after the completion of all treatments. Results: Thirty two patients (21 male and 11 female) were eligible for evaluation. A relapse was detected in 11 cases (34.4%): primary sites, 7 cases (21.9%); cervical lymph node and distant metastasis, 2 cases (6.3%); primary site and distant metastasis, 1 case (3.1%); cervical lymph node, 1 case (3.1%). Seven patients (21.9%) died. The Kaplan-Meier method was used to estimate the 3-year and 5-year survival rates, which were 81.3% and 78.1%, respectively, and the 3-year and 5-year locoregional control rates, which were 68.8% and 64.5%, respectively. No major complications such as cerebral infarctions or other neurological complications developed in any patient. Conclusions: These results of the present study demonstrate that this is a promising new treatment strategy for advanced head and neck cancer, thus contributing to patients’ QOL. No significant financial relationships to disclose.
Survival and association with time to treatment change in patients with metastatic renal cell carcinoma
Authors: Z. Liu, J. Burke, J. Zheng, J. Johnson
Journal: Journal of Clinical Oncology (2009)

e16160 Background: Metastatic renal cell carcinoma (MRCC) is associated with high mortality rates. The objectives of this study are to examine survival rates among patients using targeted therapies (Sunitinib, Sorafenib) for MRCC and the association of time to treatment change with survival. Methods: Administrative claims data from a large, US managed care plan were used to identify commercially insured and Medicare patients with newly diagnosed MRCC from 01/01/03–12/31/07 and continuous enrollment for 12 months prior to and at least 90 days after MRCC diagnosis. Survival from earliest evidence of targeted therapy (TT) was assessed through 9/16/2008. Treatment change was defined as stopping TT, switching TT or the addition of other treatments for MRCC. Results: 253 patients were identified with newly diagnosed MRCC (average age: 60.5 years; 71.5% male) who also received TT. Mean (median) survival time from initiation of therapy was 533 (507) days. A majority of those on TT (n = 205, 81.0%) experienced treatment change within 6 months after initiating the therapy; two-thirds within 30 days of therapy initiation. Unadjusted survival rates increased significantly with longer time to change in treatment (p=0.0075), with a mean survival time of 437 days for those with treatment change within 30 days and 724 days among those with treatment change 5–6 months post therapy initiation. Conclusions: Early treatment changes are associated with shorter survival times. High rates of early treatment changes indicate inadequacies in currently available targeted therapies for MRCC patients. No significant financial relationships to disclose.
Non-small cell lung cancer (NSCLC) in patients under 50: A long-term follow-up from the M. D. Anderson Cancer Center tumor registry.
Authors: E. D. Johnson, J. M. Hanneken, S. H. Taylor, M. J. Nunnelley, J. J. Erasmus, S. Swisher, D. R. Gomez, S. M. Lippman, D. D. Karp
Journal: Journal of Clinical Oncology (2010)

e18072 Background: Lung cancer is the leading cause of death in cancer medicine in both men and women. In 2009 there were 219,000 new cases of lung cancer and 159,390 related deaths. NSCLC is a dramatic illness for all patients, but is especially devastating in younger patients who could otherwise be productive and active members of their communities. Methods: We analyzed the initial treatment records of 580 patients identified from the M. D. Anderson Cancer Center tumor registry younger than 50 years of age at initial presentation, and who initially presented untreated between 1991 and 2001 and received initial treatment at MDACC. In addition, we performed the same analysis on a comparison group of 3,832 untreated patients older than 50 years at presentation diagnosed and treated during the same interval. Patients were classified according to localized, regional, or distant/metastatic disease. Results: The median age was 44 yrs with 3% of the patients under 30; 21% were age 30-39, 76% were 40-49. Histology: Adenocarcinoma (45.7%), squamous (12.8%), bronchoalveolar (5.5%), and large cell (6.7%). Pts with localized disease showed a 5- and 10-year survival of 69.4% and 61.7% respectively. Regional disease showed a 5- and 10-year survival of 31.2% and 23.6% respectively; distant disease showed 5- and 10-year survival of 4.2% and 3.1%. In addition, 33.8% received surgery, 57.7% received radiation, while only 45% received chemotherapy as part of their initial treatment (Table). Conclusions: Long-term survival in these younger patients in local and regional disease trend to improved survival in this group who would be expected to live longer than older patients just on the basis of life tables. The high rate of surgery (p value = nonsignificant) and the low rate of squamous cancer (p<0.036) in this group may suggest a continuing need for a more personalized approach. Survival comparisons of two groups Survival at 5 years <50 years ≥ 50 years Local disease 69.4% 49.1% Regional disease 31.2% 20.9% Distant disease 4.2% 4.7% Survival at 10 years Local disease 61.7% 31.1% Regional disease 23.6% 11.2% Distant disease 3.1% 2.5% Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration GlaxoSmithKline
Levels of circulating endothelial cells in relapsing glioblastoma patients responding to bevacizumab.
Authors: M. Eoli, A. Calleri, L. Cuppini, P. Mancuso, E. Prodi, S. Pellegatta, C. L. Solero, M. Bruzzone, F. Bertolini, G. Finocchiaro
Journal: Journal of Clinical Oncology (2010)

2067 Background: Bevacizumab, an anti-VEGF antibody, is active in a fraction of high-grade gliomas. Circulating endothelial and progenitor cells (CECs and CEPs, respectively), contribute to the formation of tumor vessels and their number may correlate with the degree of tumor angiogenesis. Methods: We tested this relationship in 24 patients with recurrent, high-grade gliomas (19 glioblastomas, GBM; 5 anaplastic astrocytomas, AA) treated with bevacizumab (10 mg/kg every two weeks) and Irinotecan (125 mg/m2 every two weeks for patients not on EIAEDs and 340 mg/mq for patients on EIAEDs) after approval of the Ethical Committee of the Neurological Institute C. Besta. The number and viability of CECs and CEPs were measured before treatment and every 2 months by six color cytometry. CECs were enumerated as Syto+CD45- CD31+/P1h12+ cells, CEPs as Syto+CD45- CD31+/CD133+ cells; CEC subpopulations expressing CD109 were also enumerated. Results: Median age was 53 years (range 15-66), median Karnofsky Performance Status (KPS) 70 (range 50-100), median number of prior chemotherapies 2 (range 1 to 4), median follow-up 5.5 months. Five patients had progressive disease at first MRI; 14 patients achieved partial response, 4 stable disease and one was lost to follow-up. Overall, 6M-PFS was 50% and 6M-OS 63%. Median PFS and OS were 6 and 10 months, respectively. For GBM, 6M-PFS was 47% and 6M-OS 68%. At baseline the number of CECs was significantly higher in GBM than in AA (123.4 ± 50.7 vs. 61 ± 31, p = 0.009). A significant reduction of CECs and viable CECs was only observed in GBM with a clinical and radiologic response after two months of therapy (CECs 121.6 ± 54.4 vs. 80.9 ± 60.3, p=0.05; viable CECs 33.4 ± 18.3 vs. 16.2 ± 16.4, p = 0.03). Higher levels of CD109+ CECs at baseline were observed in patients who achieved a treatment response lasting at least 4 months. Conclusions: The data encourage the investigation of the predictive value of viable CECs on a larger number of GBM treated by bevacizumab. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Roche
Benefits of Dabigatran versus Warfarin in Hypertensive Patients With Atrial Fibrillation : Results From The Re-ly Trial
Authors: Rangadham Nagarakanti, Stuart Connolly, Martina Brueckmann, Robert G. Hart, Paul Reilly, Herbert Noack, Andreas Clemens, Lars Wallentin, Salim Yusuf, Michael D. Ezekowitz
Journal: Circulation (2013)

Benefits of Dabigatran versus Warfarin in Hypertensive Patients With Atrial Fibrillation : Results From The Re-ly Trial
Timeliness of private access to intravenous (IV) cancer drugs: A Canadian analysis.
Authors: P. Douglas, S. Yunger, J. A. Maroun, J. Zabransky, M. Byrne, M. Ruzic, L. Blair, G. Georget, D. Shum, D. Milliken
Journal: Journal of Clinical Oncology (2010)

e16533 Background: In Canada, IV cancer drugs are normally funded through the public health care system and administered in hospitals and cancer centers. Drugs not publicly funded are sometimes paid for by private insurance (PRI). As most PRI plans do not cover these drugs as a general benefit, delays due to the need for special approvals can occur. Roche Canada's Patient Assistance Program (RPAP), managed by a 3rd party, assists patients and health care practitioners with timely access to private treatment through reimbursement navigation, financial assistance, private infusion clinic access, and pharmacy services. Time is required to enrol in RPAP, verify insurance coverage, and coordinate care between the public and private systems. This retrospective database analysis examines the timeliness of RPAP-assisted patient access to private treatment with bevacizumab (B) and rituximab (R). Methods: An analysis of anonymized data from RPAP for the period May 2009 to Dec 2009, highlighting timeframes between enrolment form receipt and 1st infusion, was conducted for B, R and B+R. Results: Data from B and R patients enrolling and accessing care during the target time period are summarized below. Patients who received 0 infusions or did not use PRI exclusively were excluded. Conclusions: Though PRI plans typically do not cover IV cancer drugs, the time for RPAP to secure PRI and deliver the 1st infusion proceeded quickly for most patients (∼1 month). Patients unreachable within 24 hours of enrollment form receipt and the need for special PRI appeals/employer escalations delayed OTT, making timely care difficult. Limits of this analysis are: patients may enroll but decline treatment and patients receiving infusions in hospitals are not captured in the database. Future work should study how to optimize OTT and compare the timeliness of private access via RPAP to that of the public system. n Enrollment form received to patient contacted, d n Patient contacted to insurance verified, d n Insurance verified to 1st infusion, d n Overall time to treatment (OTT), d B 73 7 (0-87) 49 1 (0-76) 25 11 (0-93) 19 2 (7-96) R 26 1.5 (0-120) 21 6 (0-58) 12 15.5 (7-43) 12 32 (9-94) B+R 99 6 (0-120) 70 3 (0-76) 37 11 (0-93) 31 29 (7-96) Days (d) shown as median (min-max). Same day service = 0 d. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Innomar Strategies Inc., Roche Innomar Strategies Inc. Roche Roche Roche