tbuckley/cabot-search huggingface dataset:
The use of innovative oncology drugs in Europe
Authors: N. E. Wilking, C. Svedman, B. Jönsson, N. Zethraeus
Journal: Journal of Clinical Oncology (2006)

16020 Background: A number of new innovative cancer drugs have recently been approved or are in the process of being approved. Rapid patient access to new innovative drugs is important as it may lead to improved survival. Methods: We have analysed the access and uptake of new oncology drugs in 19 European countries over a 15 year period based on sales data provided by IMS Health. In the study we focus on select, “targeted” drugs that have been introduced over the last 10 years: rituximab, trastuzumab and imatinib. We have also analysed data to assess the composition of the drug “arsenal” used in the selected countries based on % of total sales for cancer drugs introduced before 1993; between1993–1998 and after 1999. Results: We see different patterns of uptake in countries studied, both with respect to speed and level of usage, in relation to use per person dying of the specific cancers.. Fast uptake is seen in Austria, Switzerland and Spain, and slow uptake as well as low usage is seen in Poland, Hungary, Norway and the UK. For example, trastuzumab uptake indicates that countries with the fastest uptake treat the majority of HER2 over expressing metastatic breast cancer patients within 2–3 years after introduction while countries with slow uptake still after 5 years seem to have a large proportion of patients not receiving trastuzumab treatment. On the other hand, for a drug like imatinib the uptake has been more rapid and uniform in most countries. The composition of the cancer drug “arsenal” used also differs significantly in between countries. Conclusions: Patient access to innovative cancer drugs varies significantly between European countries. [Table: see text]
Quality of life in colorectal cancer patients with hepatic arterial infusion (HAI) pumps
Authors: V. C. Sun, R. Nelson, B. Wagman, M. Carroll, B. Lee, H. Marx, Y. Yen, L. D. Wagman
Journal: Journal of Clinical Oncology (2007)

19602 Background: More than half of patients diagnosed with colorectal cancer will develop hepatic metastases. Most patients with hepatic metastases will recur within two years after resection. Hepatic arterial infusion (HAI) pumps deliver regional treatment. However, very few studies quantitatively explore the patient's experience of living with an HAI pump and how this experience impacts HAI-related quality of life (QOL). This study explored the impact of HAI pump treatment on patient's overall QOL within the specific domains of physical, psychological, social, and functional well-being. Methods: Twenty-five colorectal cancer patients treated with HAI pumps completed an HAI pump- specific QOL assessment tool at one data collection time point. The QOL assessment tool items were derived from the investigator's previous QOL research with this patient population [Blair et al., 2002, Annals of Surgical Oncology]. Demographic, disease and QOL data were summarized using descriptive statistics. Results: Of the 25 patients accrued, 32% were receiving treatments through their HAI pump and 68% were not. There were no significant difference in QOL between treatment status, gender, and age (&lt;65 or = 65). Currently treated pump patients experienced more appetite changes (p=0.03), sleep changes (p=0.08), and more restrictions in traveling (p=0.08). Male patients had more concerns with lifting heavy items (p=0.05), while female patients had more concerns with isolation (p=0.17) and changes in the type of clothing worn (p=0.16). Younger patients had more concerns with vigorous activity (p=0.01), bending (p=0.08), and were more self-conscious of their appearance with the pump (p=0.01). Conclusions: Overall, in this study, colorectal cancer patients with HAI pumps reported good QOL and were satisfied with their overall treatment experience. Although there was no comparative statistical analysis performed in this study, several QOL concerns remain worrisome for patients. Defining these specific QOL concerns in HAI patients will enhance clinical understanding of their unique experience with this treatment modality and impact patient management. This will enable further development of educational tools and research to test interventions to support HAI patients and sustain their QOL. No significant financial relationships to disclose.
KPC-3 Klebsiella pneumoniae ST258 clone infection in postoperative abdominal surgery patients in anintensive care setting: analysis of a case series of 30 patients
Authors: P. Di Carlo, G. Gulotta, A. Casuccio, G. Pantuso, C. Mammina, C. Airo’ Farulla, S. Bonventre, G. Guadagnino, M. Scognamillo, G. Cocorullo, M. Raineri, A. Giarratano
Journal: Clinical Microbiology and Infection (2013)
N03CC—a randomized, controlled, open-label trial of upfront vs. delayed zoledronic acid for prevention of bone loss in postmenopausal (PM) women with primary breast cancer (PBC) starting letrozole after tamoxifen
Authors: B. A. Mincey, T. Dentchev, J. A. Sloan, S. L. Hines, E. A. Perez, D. B. Johnson, P. L. Schaefer, H. Liu, S. P. Kahanic, C. L. Loprinzi
Journal: Journal of Clinical Oncology (2008)

564 Background: PM women receiving letrozole after tamoxifen for PBC are at risk for significant bone loss. This study evaluated the effect of zoledronic acid on bone loss in these women. Methods: A two-arm, randomized, controlled, open-label trial assessed the effect of upfront vs. delayed zoledronic acid on bone mineral density (BMD) in PM women with PBC starting letrozole after tamoxifen. PM women with hormone receptor + PBC (stage I-IIIA), BMD T-score >-2.0, and prior tamoxifen use were stratified by duration of tamoxifen, time since tamoxifen, baseline T-score, and use of adjuvant chemotherapy. They were randomized to upfront or delayed zoledronic acid, 4 mg IV every 6 months for 5 years. All patients received letrozole 2.5mg/d, vitamin D 400 units/d, and calcium 500 mg twice/d. Women in the delayed arm with a post-baseline T-score < -2.0 or nontraumatic fracture were given zoledronic acid. The primary endpoint was the percent (%) change in total lumbar spine (LS) BMD at 1 year. A decline of 5% was defined as clinically meaningful. A two-sided two-sample t test with 500 patients had 90% power to detect a difference of 2.9% in the average % change from baseline in LS BMD between the treatment groups with a 5% type I error rate. Regression models used to incorporate covariates produced results consistent with the primary analysis. Results: 558 women enrolled, 431 with data at 1 year. Patients on the upfront arm averaged a 3.7% increase in LS BMD while the delayed arm averaged a 1.7% decrease (p<0.001). Rates of clinically meaningful decline in LS BMD for the upfront vs. delayed arm also differed markedly (3% vs. 20.7% respectively, p<0.0001). Adverse events at 1 year were similar, with slight (<3%) increases in creatinine, edema, fatigue, nausea in the upfront arm (p<0.05). BMD changes at the femoral neck and total hip were similar to those at the LS. There has been no difference in fracture rate at the hip between study arms. Conclusions: Upfront therapy with zoledronic acid prevented bone loss and improved BMD at all sites in postmenopausal women without osteoporosis starting letrozole after tamoxifen for PBC. We gratefully acknowledge support from the NCCTG (NIH CA25224) and Novartis. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration Novartis
ABC; An AGITG trial of fixed dose rate (FDR) gemcitabine (gem) and cisplatin for patients (pts) with advanced biliary tract cancer (ABC)
Authors: D. Goldstein, J. Shannon, C. Brown, N. Tebbutt, S. Ackland, G. Van Hazel, E. Abdi, M. Jefford, M. C. Gainford, K. Adams
Journal: Journal of Clinical Oncology (2007)

15015 Background: No standard regimen exists for pts with ABC. Previous studies suggest that FDR optimises gem activity. This study evaluated the activity of FDR gem with low dose cisplatin using a previously identified schedule. Methods: Single arm, multi- centre phase II trial, planned to enrol 45 pts &gt; 18 years, ECOG PS = 2, with previously untreated histologically / cytologically confirmed, inoperable locally advanced or metastatic ABC. Treatment consisted of FDR gem 1000 mg/m2 (10 mg/m2/min) and cisplatin 20 mg/m2 days 1&amp; 8 q21 days until progression or intolerable toxicity. The primary end point was response rate (RR) by RECIST. Secondary end points included tolerability and safety, progression free and overall survival (PFS, OS) and response duration (RD). Results: 50 pts were enrolled from Feb 05 to Oct 06. Mean age was 60y (39–78); 88% had ECOG PS 0–1; 54% were female. Primary sites were gall bladder 45%, biliary tree 51%, ampulla 4%. Distant metastases were present in 63%. Past treatments included biliary stent in 29%, bypass in 6%, and an external drain in 4%. With a minimum follow-up of 12 weeks, best response was a confirmed PR in 11 pts (RR 22%, 95% CI 11 - 36) and SD (after 4 cycles) in 11 pts (22%), 1 (2%) unevaluable. CA19–9 responses occurred in 6 of 33 pts (18%). Median OS was 7 mo (0.3–13), PFS 4.4 mo (0.3–13), and RD 8 mo (5–12). One year survival rate was 30%. The median number of cycles was 4 (1–16). Treatment was delayed at least once in 45% of pts; mean delay 9d. Grade 3/4 (NCI/CTC) toxicities included infection 9%, fatigue 9%, anorexia/nausea 11%, vomiting 9%, anaemia 9%, neutropenia 28%, thrombocytopenia 15%, abnormal ALP 25%, GGT 47%, AST 6%. There was 1 treatment related death (hematemesis with grade 4 thrombocytopenia). Exploratory analysis of CA 19–9 and its association with response assessment and overall survival will be presented in June. Conclusions: This combination was well tolerated. The observed response rate is consistent with the expected 35% rate and may be superior to that expected with gem monotherapy. Further testing of this dose and scheduling is warranted. The authors thank Lilly for an unrestricted grant to conduct this study. [Table: see text]
Novel biomarkers that predict survival in patients with ovarian cancer
Authors: E. V. Høgdall, L. Nedergaard, S. A. Engelholm, L. Lundvall, A. L. Petri, S. Risum, C. K. Høgdall
Journal: Journal of Clinical Oncology (2008)

22060 Background: Pre-operative cancer stage and grade are inadequate predictors of survival in patients with ovarian cancer. Methods: Pre-operative serum samples were collected with IRB approval in a study overseen by Rigshospitalet, Denmark, from 82 consecutive patients diagnosed with invasive epithelial ovarian cancer. Equalizer bead fractionation and SELDI-TOF-MS profiling was performed to identify biomarkers that might separate short-term survivors from long-term survivors. In addition, a 7 marker proteomic pattern was tested on these samples. Results: Patients were divided according to survival at one year follow-up. Among the 85 patients, 24 died within one year of initial surgery. CA125 levels were indistinguishable between the two groups (mean 1657 (95% CI 850–2643) and 1918 (666–3170) in the long and short-term survival group, respectively). Stage was significantly different (p<.05) when stages I and II were compared against III and IV. Median age was lower in the long-term survival group (72.7 vs 62.8 years, p=.0011). Proteomic analysis revealed 9 peaks with AUC>.9 in comparing survival at the one year time point. Of the nine peaks, two were present in higher levels in the short survival group, including an n-terminal fragment of C-reactive protein. One of the down-regulated peaks in the short survival group was transthyretin. From the 7 marker panel, beta 2 microglobulin was the most significant (median 6.09 (95% CI 5.9–7.3 compared to 9.88 (9.3–16.3) for long and short survival groups, respectively) with p<.0001. Conclusions: These novel biomarkers may be useful in predicting survival in patients with ovarian cancer. No significant financial relationships to disclose.
Interstitial high dose rate (HDR) brachytherapy alone for early stage prostate cancer
Authors: R. J. Mark, P. J. Anderson, T. Neumann, M. Nair
Journal: Journal of Clinical Oncology (2006)

14633 Background: Transrectal Ultrasound (TRUS) guided interstitial implant for prostate cancer using Low Dose Rate (LDR) and High Dose Rate (HDR) technique has been reported with results comparing favorably to surgery and External Beam Radiation Therapy (EBRT). Often, HDR and LDR interstitial implant is combined with EBRT. There is little published data on HDR alone. We report our results with HDR alone. Methods: Between 1997 and 2006, 167 patients with T1 and T2 localized prostate underwent TRUS guided interstitial implant. There were no Gleason Score or PSA exclusions. No patient received EBRT or Hormonal Blockade. Median Gleason Score was 7 (range: 4 to 10). Median PSA was 9.3 (2.7 to 39.8). Treatment volumes ranged from 42 cm 3 to 196 cm 3 . Treatment volume included the prostate and seminal vesicles in all cases. Our protocol for HDR alone, has called for two HDR Implants. The treatment volume received 2,250 cGy in 3 fractions prescribed to the 100% Isodose line, given over 24 hours. A 2 nd implant was performed 4 weeks later, delivering a further 2,250 cGy in 3 fractions, bringing the final dose to the prostate to 4,500 cGy in 6 fractions. Urethral dose points (12–16) were followed, and limited to ≤ 105% of the prescription dose. Results: With a median follow-up of 64 months (range: 6 months to 112 months), PSA disease free survival was 89.8% (150/167). Urethral stricture requiring dilatation has developed in 4.2% (7/167) of patients. Urinary stress incontinence has occurred in 3.6% (6/167). RTOG late bladder toxicities were: 0% Grade 4, 0% Grade 3, and 3.6% (6/167) Grade 2. RTOG late rectal toxicities were: 0.6% (1/167) Grade 4, 0% Grade 3, 1.8% (3/167) Grade 2, and 2.4% (4/167) Grade 1. There have been no cases of rectal incontinence to date. Conclusions: Five year results with HDR implant alone compare favorably to EBRT, LDR ± EBRT, and HDR + EBRT, both with regard to PSA disease free survival, and complications. HDR offers other advantages over LDR, such as no radiation exposure to hospital personnel, no seed migration, greater dose flexibility and precision of radiation dose delivery. Larger volumes can be treated with HDR. By omitting EBRT, bladder and rectal complications appear to be significantly reduced. No significant financial relationships to disclose.
A phase II study of gemcitabine with regional arterial infusion of nafamostat mesilate for advanced pancreatic cancer.
Authors: T. Uwagawa, T. Misawa, T. Gocho, T. Iida, S. Wakiyama, S. Hirohara, T. Sakamoto, K. Yanaga
Journal: Journal of Clinical Oncology (2010)

e14548 Background: Inhibition of gemcitabine-induced nf kappa b activation by synthetic serine protease inhibitor, nafamostat mesilate (NM) improved chemosensitization of pancreatic cancer to gemcitabine (GEM) in basic research. Based on such a mechanism, phase I study was conducted and recommended dose of nafamostat mesilate in combination with full-dose gemcitabine was decided as 4.8 mg/kg. Methods: Patients received gemcitabine (1,000 mg/m2 i.v. for 30 min) on days 1, 8, and 15, with nafamostat mesilate (continuous regional arterial infusion for 24 h through a port-catheter system) on days 1, 8, and 15; this regimen was repeated at 28-day intervals. Results: Thirty patients with locally advanced or metastatic pancreatic cancer were entered: male/female: 24/6; age: median 64 years (range 38-79); stage 3/4 = 9/21. No patients needed dose reduction and none developed grade 4 nonhematologic or hematologic toxicity. Median OS was 9.7 months. Treatment outcome, CR/PR/SD/PD/unevaluable was as follows; 0/6/18/4/2. Twenty-three of 26 pts showed reduction of CA19-9, of whom > 50% reduction was achieved in 11. Of 14 pts on opioid analgesics for cancer pain before this treatment, three were weaned off completely, and three required less dose of opioids. Ten patients demonstrated weight gain after this treatment. Conclusions: Combination chemotherapy of GEM with regional arterial NM achieved acceptable OS and quality of life, which could be a useful regimen for inoperable pancreatic cancer. No significant financial relationships to disclose.
The impact of platelet count (Plt#) on outcome in curable colon cancer
Authors: A. Shwaiki, A. M. Safar
Journal: Journal of Clinical Oncology (2004)

9735 Background: Proliferation of a neoplastic mass beyond ∼ 2mm requires the establishment of new blood vessels, a process termed angiogenesis, to provide oxygen and nutrients. The above applies—conceptually—both to tumor initiation and the establishment of macroscopic metastasis. Angiogenesis is thought to result from repression of antiangiogenic mediators and activation of pro-angiogenic factors, prime among them is the Vascular Endothelial Growth Factor VEGF. Platelets (Plt) contain substantial amounts of VEGF in their granules and are potential reservoirs that might facilitate tumor-promoting angiogenesis. Numerous studies support the correlation between serum levels of VEGF and inferior prognosis in multiple histologies. Because platelet lowering is readily achievable with simple pharmacologic maneuvers, it would be important to dissect the role of circulating platelets in tumor propagation mediated through angiogenesis. We hypothesized that patients with increased platelet count are at a disadvantage since this represents a milieu rich in VEGF, thus resulting in inferior curability. Methods: We retrospectively reviewed tumor registry data for stages II and III resected colon cancer. We compared the preoperative Plt# for two designated cohorts; those surviving more than 3 years (>3 yrs) vs. those succumbing in the first three years after curative resection (<3 yrs). Results: 94 patients with stage II (62 >3 years; 32 <3 years) and 49 with stage III (27 pts >3 year; 22 pts <3years) were included. As shown in the table, Plt# for the two cohorts is overlapping and indistinguishable for both stages. Conclusions: At a first approximation, correlation between Plt# and outcome does NOT appear to be present. Our results should not be taken as final. Censoring postoperative Plt# (as opposed to preoperative) and accounting for recurrence (as opposed to overall survival) are immediate considerations. No significant financial relationships to disclose.
Abstract 19702: Bending Flexibility of Stents: Comparison among Four DES Platforms with Different Design and Materials Deployed in in-vivo Simulated Cyclically-Bending Coronary Artery Model
Authors: Kiyotaka Iwasaki, Sho Kishigami, Jun Arai, Takafumi Ohba, Tadashi Yamamoto, Yutaka Hikichi, Hiroshi Kasanuki, Mitsuo Umezu
Journal: Circulation (2012)

Objective: Deployment of coronary stents in bending coronary artery often provokes changes in cyclic bending angles during cardiac contraction and relaxation. We investigated cyclic bending flexibility of four drug eluting stents consisted from different design and materials, using a novel methodology using in-vivo simulated cyclically-bending and mechanically-matched coronary artery model. Methods: Based on angiographic data of bending angles of proximal right coronary artery (RCA) in end-systole and end-diastole of 63 patients, the angle data matched to type-B according to ACC/AHA guideline were used to fabricate a RCA model. Because the average angles in end-systole and end-diastole were 105° and 125°, stents were deployed in the coronary artery models which are cyclically bended between 105° and 125°. Mechanical stiffness of the coronary artery model was adjusted to that of referenced human coronary artery. Promus Element PtCr stents (3×20mm), Resolute Integrity MP35N CoCr stents (3×18mm), Xience Prime L605 CoCr stents (3×18mm), Cypher SUS 316L stents (3×18mm) were deployed in the transparent elastic bending coronary artery mode at each nominal balloon inflation pressure (n=6 each). Bending angles of stents were analyzed using digital microscope. Results: Bending flexibility was clearly differentiated among four DES platforms as shown in the figure. These data indicated that Promus Element PtCr stents was most flexible among the four stents in response to cyclic deformation of the coronary artery model. There were significant differences in the bending angles both in end-systole and end-diastole as well as in the traveling angles. Conclusion: Cyclic bending flexibility of four DES consisted from different design and materials was quantitatively revealed using a novel methodology.
Regorafenib assessment guided by metabolic imaging in refractory advanced colorectal cancer (aCRC): REGARD-C study.
Authors: Alain Hendlisz, Amélie Deleporte, Thierry Delaunoit, Marc Peeters, Gauthier Demolin, Jos Janssens, Stephane Holbrechts, Raphael Maréchal, Javier Carrasco, Marc Van Den Eynde, Karen Paula Geboes, Jean Charles. Goeminne, Lionel A. D'Hondt, Marianne Paesmans, Caroline Vandeputte, Frederic Hoerner, Patrick Flamen
Journal: Journal of Clinical Oncology (2014)

TPS3659 Background: Regorafenib, an oral multi-tyrosine kinase inhibitor that shares with sorafenib several targets on tumor angiogenesis, oncogenesis, and tumor microenvironment, was recently approved for patients (pts) with pretreated advanced colorectal cancer (aCRC). The drug improves the pts’ outcome, but with significant toxicities, underscoring the need to identify those who will not benefit. A previous study (SoMore trial) showed that early FDGPET-based metabolic response assessment (MRA) may adequately discriminate pts with chemorefractory aCRC unlikely to benefit from a sorafenib-capecitabine combination. RegARd-C aims to explore early MRA in pts treated with regorafenib as a clinical tool to spare pts from needless toxicity from a drug that gives them little or no benefit and as a translational tool to guide comprehensive genomic and epigenetic research on the determinants of drug resistance. Methods: RegARd-C’s (EUDRACT 2012-005655-16) is a multi-centric prospective study. Its primary objective is to identify in a population of pts with pretreated aCRC, those who will not benefit from regorafenib given at 160 mg/day, three weeks/4. Baseline PET is repeated at D14 of the first treatment course. MRA results are blinded for the investigators. Tumor tissues, optionally obtained from a PET-measurable lesion, and blood samples (at baseline; after the first chemotherapy course; and every two months) are collected. Overall survival (OS) is the primary endpoint and will be correlated with metabolic parameters, and genetic, epigenetic and molecular aberrations assessed from tumor biopsies and blood samples using gene expression and methylation profiling, RNA and exome sequencing. As the study is exploratory, no formal hypothesis was formulated. We arbitrarily decided to have a sample size of 105 evaluable pts with 70 pts as a derivation set and 35 pts as a validation set. Taking into account an expected 20-25% drop-out rate, between 124 and 140 pts will be accrued.This sample size is, however, sufficient to validate the hypothesis generated by the SoMore study, which found a prognostic impact of homogeneous metabolic response on OS, with an estimated HR of 0.59. RegARd-C has accrued 76 pts since August 2013. Clinical trial information: NCT01929616.