tbuckley/cabot-search huggingface dataset:
Tipifarnib in combination with idarubicin and cytarabine in patients with newly diagnosed acute myeloid leukemia (AML) or high risk myelodysplastic syndrome (MDS)
Authors: F. Ravandi-Kashani, H. Kantarjian, G. Garcia-Manero, S. O’Brien, S. Verstovsek, Z. Estrov, S. Faderl, F. Giles, J. Wright, J. Cortes
Journal: Journal of Clinical Oncology (2006)

6557 Background: Tipifarnib (Zarnestra [Z]) is a non-peptidomimetic farnesyl transferase inhibitor (FTI) with clinical activity in AML and MDS. In vitro studies have demonstrated synergy when combining tipifarnib with chemotherapeutic agents. Methods: We have conducted a study where pts (aged 15 to 60 years) with previously untreated AML or high-risk MDS (blasts &gt;10%) were treated with Idarubicin 12 mg/m 2 /d on days 1–3, cytarabine 1.5 g/m 2 IV over 24 hours daily on days 1–4 and Z; the first cohort (7 pts) received Z 200mg orally twice daily (BID), and all others 300 mg BID for 21 days. Pts achieving CR received consolidation (5 courses) with Idarubicin 8 mg/m 2 /d on days 1–2, cytarabine 0.75 g/m 2 /d on days 1–3, and Z 300 mg BID for 14 days every 4–6 weeks. Maintenance was with Z 300 mg BID for 21 days every 4–6 wk for 6 months. Results: We have treated 33 pts; median age 51 yrs (17–59 yrs). Twenty two pts (67%) have achieved CR, 3 (9%) CRp, and 2 (6%) PR. There were no induction deaths. Response (CR/CRp) by cytogenetics was: 13/15 (86%) for diploid, 5/6 (83%) with −5/−7, 1/2 (50%) with t(8;21), and 6/10 (60%) with other abnormalities. Response by Flt3 was 19/22 (86%) for unmutated Flt3, 3/5 (60%) for mutated Flt3. CR by age (excluding t(8;21)) was 13/16 (81%) if ≤ 50yrs, 4/6 (67%) if &gt;50yrs and diploid, and 5/8 (63%) if &gt;50yrs and other cytogenetics. With a median follow-up of 45 weeks, 5 pts have relapsed after 13 to 39 weeks and 1 died (in CR) after 18 wks. The most common grade 3 adverse events include reversible diarrhea in 7 (21%) and hyperbilirubinemia in 6 (18%). Twenty (61%) and 8 (53%) pts have required dose reductions during induction and consolidation courses, respectively. Conclusions: Z combined with Idarubicin and cytarabine induces a high rate of CR in AML/high risk MDS, with increased incidence of diarrhea and hyperbilirubinemia. Role of Z in prolongation of CR duration requires further follow-up. [Table: see text]
A phase I trial of E7974 administered on days 1 and 15 of a 28-day cycle in patients with solid malignancies
Authors: S. Madajewicz, N. J. Zojwalla, A. G. Lucarelli, P. Hentschel, J. Giardelli, E. L. Schuck, I. Krivelevich, B. Y. Wong, N. J. Vogelzang, S. Sharma
Journal: Journal of Clinical Oncology (2007)

2550 Background: E7974 is a synthetic hemiasterlin analogue exhibiting binding to a and β tubulin. It induces disruption of spindle formation and mitotic arrest characteristic of anti-tubulin cancer drugs. Unlike taxanes and vincas, E7974 is a poor substrate for the PgP drug efflux pump, potentially overcoming this common mechanism of drug resistance. E7974 demonstrates broad anti-tumor activity against a variety of human tumor xenografts. Methods: An accelerated phase I dose escalation design was used to determine the maximum tolerated dose (MTD) and pharmacokinetic (PK) profile of E7974 administered IV over 2–5 minutes on Days 1 and 15 of a 28-day cycle. Results: Seventeen patients (14 male, 3 female) with a median age of 59 yrs. (range: 42–77 yrs.) were treated at doses of 0.18 mg/m 2 , 0.25 mg/m 2 , 0.31 mg/m 2 , and 0.39 mg/m 2 . Patients with colorectal (6), esophageal (3), prostate (2), urothelial (2), NSCLC (2), and other (2) cancers were enrolled. At the 0.39 mg/m 2 dose level, one patient experienced grade 3 neutropenia and 2 patients experienced grade 4 neutropenia. The 0.31 mg/m 2 dose was declared the MTD. Additional drug related toxicities (grade 1–2) included fatigue (8 pts.), constipation (4 pts), neuropathy (3 pts.), diarrhea (2 pts.), flushing (2 pts.) and myalgia (1 pt.). One patient with esophageal cancer had a partial response at the 0.39 mg/m 2 dose level and one patient with prostate cancer had &gt;50% decline in PSA and significant clinical benefit for &gt;4 months at the 0.31 mg/m 2 dose level. Stable disease was seen in two patients, one with esophageal cancer (8 cycles) and one with colorectal cancer (4 cycles). The PK profile of E7974 was characterized by moderate to large distribution (Vss = 55 - 187 L), slow clearance (CL = 1.99 - 8.77 L/hr) and moderate to slow elimination (t 1/2 = 11.9 - 31.6 hr). Approximately 26 - 85% of the administered dose of E7974 was recovered unchanged in the urine 48 hours post-dose. Conclusions: The recommended phase 2 dose of E7974 on days 1 and 15 of a 28-day schedule is 0.31mg/m 2 . Observed toxicities were manageable and reversible. No significant financial relationships to disclose.
Melanoma recurrence risk stratification using Bayesian systems biology modeling.
Authors: Edda Lind Styrmisdottir, Patrick Scanlon, Douglas Hanniford, John Eberhardt, Thomas Jones, Eva Hernando, Iman Osman
Journal: Journal of Clinical Oncology (2013)

9089 Background: Estimating the risk of recurrence in patients with melanoma is extremely challenging. Standard of care is AJCC staging system, but the accuracy and robustness of this method is still under development. We conducted a proof of concept study exploring the use of machine-learned Bayesian Belief Networks (ml-BBNs) using a miRNA profiled cohort of melanoma patients with extended follow up to create Bayesian Biological Systems Models (BBSMs). We sought to determine if ml-BBNs could describe the biological system and if we could use the model to identify new cases with higher risk of recurrence. Methods: Our study cohort consisted of 89 patients (42 of which recurred) with a median follow up time of 118 months, that were examined for 869 miRNAs. Prior to modeling we segmented the data into training data (72 cases/80%) and testing data (17 cases/20%) at random. We recursively trained ml-BBNs on the training set, using all miRNAs. We used the directed graph structure of the ml-BBNs to identify miRNAs that consistently had more connectivity and goodness of fit as determined by Bayesian Information Criteria (BIC) scoring. MiRNAs that were in the top 50 BIC-scoring nodes across all models were selected for use to train the recurrence BBSMs. To compensate for a small number, bootstrapping was used to increase the sample to 100 records. We then compared our test set cases to our recurrence model, and used a similarity scoring algorithm to evaluate the similarity of values in each test instance to our biological models. For comparison we also trained an ml-BBN using clinical data from the same cohort. We then evaluated the scores against known recurrence outcome using Receiver Operating Characteristic (ROC) curve analysis. Results: BIC-scoring analysis selected 35 miRNAs for use in BBSM modeling. Area Under the Curve (AUC) for detection of recurrence is 0.76 in the training set and 0.62 in the testing set, while the clinical data yielded an AUC of 0.5 in this cohort. Conclusions: Our data suggest that ml-BBNs can be used to describe a biological model of melanoma recurrence. Additional data and refinement need to be made using independent datasets to be of a level that is clinically useful.
A phase II study in patients with advanced biliary tract carcinoma (BTC) treated with hepatic arterial infusion chemotherapy (HAI) with oxaliplatin (O), 5-fluorouracil (5FU), and folinic acid (FA).
Authors: A. Nicolaou, M. Sinn, B. Hildebrandt, B. Gebauer, J. Ricke, B. Dörken, H. Riess
Journal: Journal of Clinical Oncology (2010)

e14512 Background: Unresectable BTC has a poor prognosis. Systemic chemotherapy with gemcitabine and cisplatin is an effective treatment option as recently demonstrated but with systemic side effects. Tumour growth in these patients (pts) is often restricted to liver, so HAI may be considered. Methods: In consecutive pts with histologically confirmed advanced inoperable BTC without relevant distant metastases catheters were interventionally placed in A. hep. via A. fem. sup. and connected to a port chamber on the front of the tight. HAI of 5FU 600 mg/mq/2h combined with FA 170 mg/mq/2h followed by O 85 mg/mq/2h were given every 2 weeks. Pts were followed prospectively with regard to port complications, response rate, TTP and OS. Results: By end of December 2009, 37 pts (15 men; 13 after partial liver resection; 6 after systemic chemotherapy) were included. Median age was 62 years (range 41-79), median follow up is 9.5 months, median treatment duration 6.2 months (0.5-22.7). III° toxicity occured in 9 pts (1 diarrhea, 1 PNP, 1 nausea, 2 leukopenia, 4 thrombopenia). 9 pts developed manageable port complications (3 thrombosis, 4 dysfunction, 1 malposition, 1 arterial spasm). End of treatment was due to tumour progression in 29 pts, to port complication (infection) preceding PD in 2 pts. 7 pts developed intra-hepatic progression, 5 showed new extra-hepatic metastases and 17 both. There were 6 PR and 18 SD. Median TTP was 6.4 months (0.5-26.0). Median OS was 10.0 months (0.9-49.0+), 1year-survival 43%. Conclusions: In pts with BTC restricted to the liver, HAI is a promising treatment approach. Prolonged HAI chemotherapy with oxaliplatin, 5-FU/FA is feasible and well tolerated. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Amgen, AstraZeneca, Bayer, Boehringer Ingelheim, C.R. BARD, Cook, Fresenius Biotech, GlaxoSmithKline, Lilly, Merck, Pfizer, Roche, sanofi-aventis Amgen, Merck, Roche, sanofi-aventis
The effects of death education used in a master's degree in palliative care on attitudes toward caring for terminally ill patients.
Authors: S. De Santis, F. De Marinis, C. Mastroianni, G. Casale
Journal: Journal of Clinical Oncology (2011)

e19549 Background: The challenge of achieving an objective evaluation of End of Life Care educational outcomes, remains an open question. This study sought to determine the effectiveness of an education program used in a master's degree in Palliative Care. The program, developed in Italy at “Tor Vergata” University of Rome and at ANTEA Formad of Rome, included a didactic and the experiential death education. The didactic approach (involving, for example, lectures and audiovisual presentations) is meant to improve knowledge. The experiential approach (including personal sharing of experiences in group discussion, role-playing, and a variety of other simulation exercises) is used to actively involve participants by evoking feelings and thereby permitting death-related attitudes to be modified. Methods: The Frommelt Attitude Toward Care of the Dying Scale (FATCOD) FormB italian version, and demographic questionnaire that includes sex, age, occupation, years of service, previous work experience with the terminally ill, were designed by the researcher to assess attitudes. Participants were administered the questionnaires at the time of placement tests and at the end of the course. Results: Data were collected from 21 partecipants, 16 physicians and 5 nurses, female 76%, 43% aged 36 to 45, 42% worked in palliative care, 63% seniority for ≥ 5 years, with more than 76% of working experience with the terminally ill patients. All partecipants completed the tool. Compared by a t-test, the scores were significantly higher after participation in this educational program. These findings support the hypothesis that partecipants have a more positive attitude toward caring for terminally ill patients after their participation in this program. The only demographic information which demonstrated any significant relationship to the attitudes was that of age, professional experience and previous education on death and dying. Conclusions: The FATCOD FormB was found to be a valid and reliable tool. The Tor Vergata - Antea master's degree in Palliative Care provides sufficient time to address the complex issues of death attitudes and to bring about attitude changes.
Skin rash as surrogate marker of efficacy in patients with non-small cell lung cancer treated with erlotinib
Authors: M. Cobo, F. Cardenal, A. Insa, M. Domine, P. Lianes, M. Guillot, J. Montesinos, I. Bover, M. L. Amador, L. Paz-Ares
Journal: Journal of Clinical Oncology (2007)

7602 Background: Erlotinib is an orally EGFR TKI approved for the treatment of advanced non-small-cell lung cancer. Its most frequent and specific toxicity is a rash which generally occurs in a dose-dependent manner. A relationship between rash and clinical outcome have been suggested. Methods: The TargeT trial was an open-label, non-randomized, phase II study carried out in 101 Spanish institutions. Patients (p) with confirmed NSCLC (stage IIIB-IV) were treated with 150 mg/day po until disease progression or unacceptable toxicity. Primary objective was time to progression. Here we report a retrospective analysis describing outcomes in terms of response and survival in the group of patients who developed rash and those who did not. Results: Data were available for 1,255 p. Key baseline characteristics were similar in p with and without rash. Median age 65y (range 26–95) Most p were male (75%); active/former smoker (82%) 51% adenocarcinoma histolog. ECOG PS 0/1/2 were (%) 20/53/27. The % p receiving erlotinib as 1st/2nd/3rd- line treatment were 26/39/35. 698 patients were evaluable for response. Objective response rate (ORR) 12.6% with 51% control disease rate. Skin rash of any grade was observed in 73.4% p, among these p, responses were observed in 14.3%. In p with no rash ORR was 8.1% (p=0.03). Control disease rate was significantly higher among p experiencing rash (56.6%) than those without rash (35.48%; p&lt;0.0001). Median time to progression for p with rash were 3.8 mo (95% CI: 3.4–4.3), compared with 2.3 mo (95% CI: 2.1–2.6) in those with no rash (p&lt;0.001). Similar trend was found in overall survival 6.5 mo (95% CI: 6.1–7.3) in p with rash versus 2.3 mo (95% CI: 2.3–2.7; p&lt;0.001). In addition p who developed rash grade =2 had significantly longer TTP (4.2 m; 95% CI 3.6–4.8; p&lt;0.001) and OS (7.9 mo; 95% CI 6.5–8.8). Conclusions: This retrospective analysis suggest a correlation between skin rash development and severity and treatment outcome. Skin rash seems to be a surrogate marker of efficacy. Studies to prospectively investigate the association between increased dosing of erlotinib, skin rash and optimal response are currently ongoing. However, data from our analysis indicate that skin toxicity is neither sufficient nor necessary condition for an optimal outcome. No significant financial relationships to disclose.
Phase II trial of gemcitabine, paclitaxel, and cisplatin in advanced transitional cell carcinoma
Authors: P. E. Clark, D. Stindt, M. C. Hall, M. Harmon, J. F. Lovato, R. Mohler, C. Kimbrough, F. M. Torti
Journal: Journal of Clinical Oncology (2004)

4610 Background: We present interim results of a phase II trial of gemcitabine, paclitaxel, and cisplatin (GTP) for advanced urothelial cancer. Methods: Patients with advanced TCC (unresectable local or metastatic disease) were given gemcitabine (800–900 mg/m2 day 1 & 8), paclitaxel (125 mg/m2day 1), and cisplatin (75 mg/m2 day 1) every 3 weeks for up to 6 cycles with growth factor support as required. Both pure TCC as well as TCC with mixed histologies were permitted. Response was evaluated utilizing RECIST criteria. Results: 38 patients (27 men, 11 women) were registered. Mean age was 63 (range 29–85) years. TCC primary was in the bladder (N=33), renal pelvis (N=2), or ureter (N=3). Sites of metastases at entry included lung (N=11), liver (N=6), and bone (N=6). 18 patients had more than one metastatic lesion. Six patients are too early in therapy to be evaluated for response. One patient had invasion of the diaphragm and colon but not bi-dimensional disease on CT scan. One patient refused therapy after registration but is included in the survival analysis on an intent-to-treat basis. One patient died of treatment related toxicity before response could be evaluated. Of the 29 patients currently eligible for response evaluation, 7 have had a complete response(24%), 8 a partial response (28%) for an overall response rate of 52%. 6 patients have had stable disease (21%) and 8 disease progression (28%). Median overall survival for all 38 patients was 10.7 months, while median progression free survival among 32 patients evaluable for progression was 7.5 months. Toxicity was generally manageable. One patient died of treatment related toxicity on day 20 of the first cycle of GTP from neutropenia and sepsis. One patient with previous hearing loss had grade 4 neuro-hearing toxicity. Two patients had grade 3 neurosensory toxicity. Seven patients had grade 4 neutropenia, and two had grade 4 thrombocytopenia. Conclusions: A combination of gemcitabine, paclitaxel, and cisplatin for advanced TCC is tolerable with an excellent complete response rate. Toxicity was limited, and neurotoxicity, in particular, was manageable. This regimen shows promise and warrants further study. No significant financial relationships to disclose.
Phase II Trial of High-Dose Liposome-Encapsulated Doxorubicin With Granulocyte Colony-Stimulating Factor in Metastatic Breast Cancer
Authors: C. L. Shapiro, T. Ervin, L. Welles, N. Azarnia, J. Keating, Daniel F. Hayes
Journal: Journal of Clinical Oncology (1999)

PURPOSE: To estimate the toxicity and response rate of high-dose liposome-encapsulated doxorubicin (TLC D-99, Evacet, The Liposome Company Inc, Princeton, NJ) in patients with advanced breast cancer. PATIENTS AND METHODS: Fifty-two breast cancer patients with bidimensionally measurable metastatic disease and no prior chemotherapy for metastatic disease received a 135 mg/m 2 intravenous (IV) bolus of TLC D-99 with 5 μg/kg of granulocyte colony-stimulating factor via subcutaneous injection every 21 days. RESULTS: The median number of treatment cycles of TLC D-99 was three (range, one to 10 cycles), and the median total cumulative dose of TLC D-99 was 405 mg/m 2 (range, 135 to 1,065 mg/m 2 ). Grade IV neutropenia, thrombocytopenia, and mucositis were experienced by 48 (92%), 46 (88%), and 10 (19%) patients, respectively. Twenty (38%) of patients experienced cardiac toxicity: four (8%) experienced a decrease of 20% or more in left ventricular ejection fraction (LVEF) to a final value ≥ 50%, nine (17%) experienced a decrease of 10% or more in LVEF to a final value less than 50%, and seven (13%) developed symptomatic congestive heart failure (CHF), including one patient who died of cardiomyopathy after receiving a total dose of 1,035 mg/m 2 . In a stepwise logistic regression model, the significant risk factors for the development of CHF were the cumulative dose of prior adjuvant doxorubicin (P = .007) and the total cumulative dose of TLC D-99 (P = .032). The overall response rate was 46% (95% confidence interval [CI], 32% to 61%) on an intent-to-treat basis. The median duration of response was 7.4 months (95% CI, 6.1 to 19.6 months) and the median progression-free survival was 6.1 months (95% CI, 5.4 to 7.5 months). CONCLUSION: There was no added therapeutic benefit to the dose escalation of TLC D-99 in this study. A high rate of cardiotoxicity was also observed, especially among patients who had received prior adjuvant doxorubicin. This was probably attributable to the dose and schedule of TLC D-99 used in this trial, as well as the patient's lifetime cumulative doxorubicin dose. Administration of high-dose TLC D-99 at 135 mg/m 2 every 3 weeks by IV bolus infusion does not warrant further investigation.
AVAST-M: Adjuvant bevacizumab as treatment for melanoma patients at high risk of recurrence.
Authors: Philippa Corrie, Andrea Marshall, Madusha Goonewardena, Janet A. Dunn, Mark R. Middleton, Paul D. Nathan, Martin Eric Gore, Neville Davidson, Steve Nicholson, Charles G. Kelly, Maria Marples, Sarah Danson, Ernest Marshall, Stephen Houston, Ruth E. Board, Ashita Marie Waterston, Jenny Nobes, Mark Harries, Jim Barber, Paul Lorigan
Journal: Journal of Clinical Oncology (2013)

LBA9000 The full, final text of this abstract will be available at abstract.asco.org at 7:30 AM (EDT) on Saturday, June, 1, 2013, and in the Annual Meeting Proceedings online supplement to the June 20, 2013, issue of Journal of Clinical Oncology. Onsite at the Meeting, this abstract will be printed in the Saturday edition of ASCO Daily News.
Abstract 15317: Automatic Quantification and Characterization of Coronary Plaque with Computed Tomography Coronary Angiography: A Comparison with Intravascular Ultrasound Virtual Histology
Authors: Michiel A de Graaf, Alexander Broersen, Pieter H Kitslaar, Jouke Dijkstra, Johan H Reiber, Jeroen J Bax, Arthur J Scholte
Journal: Circulation (2012)

Purpose Several studies have identified plaque characteristics on CTA associated with plaque vulnerability. At present only visual assessment of plaque characteristics is possible. An accurate quan...
Serum biomarkers for early detection of lung cancer.
Authors: B. Nolen, A. Lomakin, W. L. Bigbee, J. Siegfried, A. Lokshin
Journal: Journal of Clinical Oncology (2010)

e21057 Background: Lung cancer is the most common cause of cancer death in the developed world with 5-year survival rates that have remained dismal over the past decade despite significant advancements in screening and treatment methodologies. This lack of improvement can be largely attributed to an inability to detect early-stage disease leading to a preponderance of advanced disease at diagnosis, for which treatment is less successful. The measurement of serum biomarkers offers a promising means of early detection. The current lack of a serum biomarker for the detection of lung cancer mandates the development of improved methods of biomarker identification. Methods: We performed an analysis of 70 cancer-related biomarkers, utilizing Luminex xMap technology, in the sera of patients diagnosed with lung cancer, benign lung conditions, and healthy controls. Non-small cell lung cancer (NSCLC) cases consisted of 33 patients diagnosed with adenocarcinoma and 29 patients diagnosed with squamous carcinoma of the lung. Benign controls were 43 patients diagnosed with a spectrum of non-malignant lung conditions. The study population also included 142 healthy controls matched to the cancer patients on the basis of age, gender, and smoking history who had undergone lung CT and were known to be cancer free for at least 3 years. Results: Our biomarker analysis identified 20 biomarkers, representing diverse biochemical functions, whose levels differed significantly between the cases and controls. A multivariate analysis of our biomarker results yielded several multimarker panels that could differentiate cases from controls with high sensitivity (SN) and specificity (SP). A four-biomarker panel could discriminate lung cancers from the healthy control set with 85% SN at 90% SP. This panel performed similarly in distinct training and validation sets within the combined set. Another four- biomarker panel was able to discriminate the combined NSCLCs from the benign controls with 90% SN at 75% SP. Conclusions: Our serum biomarker findings support the notion that this type of screening may lead to significant improvements in our ability to detect lung cancer at a treatable stage while also offering insight into the underlying molecular processes involved. No significant financial relationships to disclose.