tbuckley/cabot-search huggingface dataset:
Carboplatin &amp; gemcitabine repeating doublet in recurrent breast cancer
Authors: R. A. Nagourney, J. Link, B. Sommers, W. Lyons, J. Blitzer, S. Hager, M. Flam
Journal: Journal of Clinical Oncology (2004)

851 Background: We previously reported a 50% objective response rate for the Cisplatin (Cis) & Gemcitabine (G) doublet in recurrent breast cancer (BC) (Nagourney, RA. J Clin Oncol, 2000). Our comparative studies in human tumors have shown similar degrees of synergy for Cis & G and Carboplatin (Carbo) & G (Evans SS, Proc ASCO, 2001). To examine the activity and tolerance of Carbo & G as a repeating doublet, a Phase II trial in recurrent BC was undertaken. Methods: Patients with 1st or 2nd relapse, measurable BC, performance status ≤ 2 and no known brain metastases were eligible after signing informed consent. To approximate the original Cis & G doublet, patients received Carbo AUC = 2.0 (Calvert) & G @ 800 mg/m2 both given days 1&8 Q21 day. Growth factors were allowed. Results: By December 2003, 12 patients were accrued with 10 evaluable and 2 excluded for brain metastases detected at cycle I. Toxicities, primarily hematologic, were manageable with scheduled dose reductions. Per patient, there were 6/10 (60%) Gr 3/4 neutropenia; 4/10 (40%) Gr 3 /4 thrombocytopenia & 2/10 (20%) Gr 3/4 anemia. There were no Gr 3/4 alopecia, neuropathies or treatment related deaths. Responses were observed in 5/10 patients (50%) with 1 CR (10%); 4 PR (40%); 2 stable & 3 disease progressions. Median time to progression was 5 months (range 2–20 months). Conclusions: Carbo & G is active in recurrent BC. While the preponderance of heavily pre-treated patients in the original Cis & G study make direct comparisons problematic, comparable degrees of activity have been observed, thus far. Appropriately adjusted Carbo doses (AUC = 2) can be safely administered with G in the repeating doublet schedule. Platinum salt & G therapies, Cis or Carbo-based, offer attractive options for recurrent BC. Future studies will help to define the optimal drug and dose schedule. Supported by a grant from Eli Lilly & Co. Indianapolis, Indiana. Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Eli Lilly & Co. Eli Lilly & Co.
Fosfomycin prevents cisplatin-induced ototoxicity: Results of a randomized, double blind, placebo controlled trial
Authors: D. Green, M. Chavez-Mac Gregor, R. Sosa-Sanchez, R. Andraca, L. Enriquez, E. Leon, S. Ponce de Leon
Journal: Journal of Clinical Oncology (2007)

9041 Background: Cisplatin is one of the most frequently used chemotherapy agents. The main dose-limiting toxicity for its use is hearing-loss, present in 40–100% of patients. To date, no treatment has proven efficacy in preventing or reducing cisplatin acoustic damage. Fosfomycin, acting as a free-radical scavanger, has shown to reduce cisplatin-induced ototoxicity and nephrotoxicity in animal models, without affecting its antineoplastic activity. This trial evaluated the effect of fosfomycin in cisplatin-induced ototoxicity. Methods: 22 chemotherapy naive patients with normal audition, scheduled to receive cisplatin-based chemotherapy (cumulative dose =200mg/m 2 ) were randomized to receive placebo (n=11) or 1g of IV fosfomycin concurrent with each cisplatin administration (2–4 cycles). Primary outcome was ototoxicity when comparing audiometric studies (low and high frequencies and otoaccustic emissions) at baseline and at completion of chemotherapy. With β=0.8 and a=0.05 the study was powered to detect differences =20 dB at any given frequency. Fisher's test, Wilcoxon and Mann-Whitney test were used. Results: Groups were balanced for baseline characteristics, cisplatin dose and response rates. No differences were found when comparing ototoxicity at low frequency ranges. When analyzing high frequencies and otoaccustic emissions, 9 patients (82%) in the placebo group developed ototoxicity vs 4 (36%) in the fosfomycin group (p=0.04). The degree of hearing-loss, evaluated by comparing percentage of change in each evaluated frequency, was significantly lower in patients receiving fosfomycin (p=0.04). Other chemotherapy toxicities were similar in both groups. Conclusions: In patients with audiometric integrity, the concurrent administration of fosfomycin with cisplatin significantly reduces ototoxicity. The degree of hearing-loss is lower in patients receiving fosfomycin than in those receiving placebo. The use of fosfomycin in combination with cisplatin is safe and does not interfere with its antineoplastic activity. To our knowledge this is the first clinical-trial that demonstrates prevention and reduction of cisplatin-induced hearing-loss. No significant financial relationships to disclose.
A randomized, open-label, phase II study of anti-NaPi2b antibody-drug conjugate (ADC) lifastuzumab (Lifa) vedotin (DNIB0600A) compared to pegylated liposomal doxorubicin (PLD) in patients (pts) with platinum-resistant ovarian cancer (PROC).
Authors: Susana N. Banerjee, Amit M. Oza, Michael J. Birrer, Erika Paige Hamilton, Jurjees Hasan, Alexandra Leary, Kathleen N. Moore, Beata Mackowiak-Matejczyk, Joanna Pikiel, Isabelle Ray-Coquard, Peter Trask, Kedan Lin, Anjali Vaze, YounJeong Choi, Jim Marsters, Daniel J. Maslyar, Vanessa Lemahieu, Yulei Wang, Eric William Humke, Joyce F. Liu
Journal: Journal of Clinical Oncology (2016)

5569 Background: NaPi2b is a transmembrane, sodium-dependent phosphate transporter expressed in ~90% of OC. Lifa, a humanized anti-NaPi2b monoclonal antibody conjugated to the anti-mitotic agent MMAE, was investigated in OC. Methods: The Phase 2 study evaluated the efficacy and safety of lifa at 2.4 mg/kg given intravenously (IV) every 3 weeks (q3w), compared to PLD (40 mg/m2 IV) given q4w, in pts with PROC. The primary endpoint was progression-free survival (PFS) assessed by investigators in intent to treat (ITT) and in NaPi2b-high (IHC 2+/3+) patients. Secondary endpoints included PFS by independent review, safety, and patient-reported outcomes. Tumor NaPi2b expression was assessed by immunohistochemistry (IHC) and quantitative PCR in archival tissue. Results: 95 pts were randomized (47 lifa; 48 PLD). For both arms, the median age was 62, and the median number of prior systemic therapies was 2. 87% of lifa and 85% of PLD pts had no prior PROC therapy. The stratified PFS hazard ratio was 0.78 (95% CI: 0.46-1.31, p = 0.34) with a median PFS of 5.3 months (lifa) vs. 3.1 months (PLD) in the ITT population, and 0.71 (95% CI: 0.40-1.26, p = 0.24) with a median PFS of 5.3 months (lifa) vs. 3.4 months (PLD) in NaPi2b-highpatients. The objective response rate was 34% (95% CI: 22-49%, lifa) vs. 15% (95% CI: 7-28%, PLD) in the ITT population, and 36% (95% CI: 22-52%, lifa) vs.14% (95% CI: 6-27%, PLD) in NaPi 2+/3+ patients per RECIST v1.1. Subgroup analyses demonstrated most benefit in the highest quartile of NaPi2b expressers. Toxicities were: Grade ≥ 3 AEs (46% lifa; 51% PLD), serious AEs (30% lifa; 30% PLD), and AEs leading to discontinuation of drug (9% lifa; 13% PLD). Grade ≥ 2 neuropathy was reported in 5 (11%) lifa patients vs. 2 (4%) receiving PLD. Global HRQOL showed no decline in the lifa arm and a clinically significant decline in the PLD arm over 24 weeks. Conclusions: This is the first randomized study of an MMAE ADC compared to standard of care in PROC. Lifa q3w was well-tolerated with improved ORR and a trend towards increased PFS compared to PLD. These data support using an ADC to target NaPi2b in OC. Clinical trial information: NCT01991210.
Distinguishing characteristics of difficult-to-control asthma in inner-city children and adolescents
Authors: Jacqueline A. Pongracic, Rebecca Z. Krouse, Denise C. Babineau, Edward M. Zoratti, Robyn T. Cohen, Robert A. Wood, Gurjit K. Khurana Hershey, Carolyn M. Kercsmar, Rebecca S. Gruchalla, Meyer Kattan, Stephen J. Teach, Christine C. Johnson, Leonard B. Bacharier, James E. Gern, Steven M. Sigelman, Peter J. Gergen, Alkis Togias, Cynthia M. Visness, William W. Busse, Andrew H. Liu
Journal: Journal of Allergy and Clinical Immunology (2016)
Early economic benefits of gene expression profiling using a 21-gene panel among patients with early stage, lymph node negative, hormone receptor positive, her2-neu oncogene negative breast cancer.
Authors: Stanley E. Waintraub, Donna M. McNamara, Deena Atieh Graham., Andrew Pecora, John Min, Tommy Wu, Hyun gi Noh, Jacqueline Connors, Ruth Pe Benito, Kelly Choi, Eric V Schultz, Stuart L. Goldberg
Journal: Journal of Clinical Oncology (2016)

e18255 Background: Gene expression profiling (GEP) utilizing a 21-gene panel assay among breast cancer patients with early stage, axillary lymph node negative, hormone receptor positive, HER2/neu oncogene negative tumors is able to identify a cohort with excellent long term outcomes without adjuvant chemotherapy. Although economic models have suggested acceptable QALY ratios, “real world” confirmation is scant and few studies have focused on the short-term costs important in value-based payment reform. Methods: A retrospective review of 227 consecutive patients, aged < 70, with early stage breast cancer at a single institution. Cost data extracted from the chart reflected actual costs not charges. Results: 68% underwent GEP with 52%, 43% and 5% having low, intermediate and high recurrence scores. By multivariate analysis GEP was applied more frequently in patients without lymph node micro-metastasis. Adjuvant chemotherapy was utilized less in genomic profiled cohorts (19% vs 29%; p = 0.08) and followed GEP recurrence scores. The mean actual 6-month outpatient costs were $24,955 with adjuvant chemotherapy and $2,654 with hormonal therapy. Stage II patients undergoing GEP received adjuvant chemotherapy at a lower frequency (28.6% vs 86.7%); but stage I patients with testing received slightly more chemotherapy (15.8% vs 14%). Universal GEP testing of stage II patients would result in net savings $11,494 per patient inclusive of the cost of the test; stage I testing increased costs by $4505. Similar trends of decreased costs for universal GEP testing of grade II/III tumors ($2394) but increased for grade I tumors ($6047) were noted. Conclusions: Universal GEP testing of stage II or grade II/III lymph node negative breast cancers resulted in lower outpatient costs inclusive of the diagnostic test within the first 6 month episode of care. Among patients with stage I disease GEP identifies a small group of “higher risk” patients who may derive clinical benefit from adjuvant chemotherapy who otherwise might not have been treated, with acceptable QALY ratios. Inclusion of hospital/relapse costs would further support GEP.
BCR-ABL monitoring in imatinib-treated patients with chronic myelogenous leukemia.
Authors: A. H. Teitelbaum, H. J. Henk, V. Bollu
Journal: Journal of Clinical Oncology (2010)

6575 Background: Current NCCN guidelines recommend baseline and q 3 mo BCR-ABL fusion transcript levels in imatinib (IM)-treated chronic myelogenous leukemia (CML) responding to treatment (tx) to monitor response, predict relapse, and confirm compliance to tx. Observance of these guidelines, introduced in Oct 2006, might be less than uniform (Stanek et al., 2009 ASCO). The objective of this study is to assess frequency of BCR-ABL testing in real-world clinical practice and study factors associated with such testing in this population. Methods: We conducted a retrospective cohort analysis using claims data from a large U.S. commercial health plan representing approximately 14 million members annually. Patient (pt) data from several calendar yrs were combined to understand evolution in use of BCR-ABL testing in routine clinical practice. The study cohort was defined as pts with an index IM pharmacy claim from 1/1/02 to 12/31/08 who had a CML Dx (ICD-9 205.1X; N=1,543), and a min. of 6 mo with no prior use of IM and 12 mo of continuous f/u by claims history (N=606). Over a period of up to 12 mo from the index IM prescription date, BCR-ABL testing was assessed by presence of any of 19 CPT-4 codes specific to BCR-ABL testing. Frequency/timing of BCR-ABL testing in the 12 mo after the index date were measured. Results: The overall study cohort was 55% male; mean (±SD) age 52.8 ± 15.5 yr (26% aged 19-44 yr, 51% =45-64 yr, 21% ≥65 yr). No BCR-ABL testing was recorded for 62% of pts in the 1st yr after starting IM; at least 1 BCR-ABL test was noted for 38% of pts, and >3 BCR-ABL tests for 15% in the 12-mo period. Pts with 3 or more tests were younger and more likely to be female (Table). Conclusions: In this retrospective claims database analysis, only 8% of a large cohort of IM-treated CML had claims evidence of 4 BCR-ABL tests in the yr after IM initiation. Inadequate adherence to guidelines for treatment response monitoring could have potential negative effects on clinical outcomes. 3+ BCR-ABL tests (N=92) 1-2 BCR-ABL tests (N=136) 0 BCR-ABL tests (N=378) Age (mean, sd) 47.65 13.91 55.14 12.96 53.25 16.39 Gender (n, % female) 49 53.26 52 38.24 169 44.71 Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Novartis Novartis
Overall Management, Outcomes and Costs on a 4-Year Period of 21,757 Acute Leukemia (AL) Patients in France. Data Report from the National Health Registry
Authors: Franck E. Nicolini, Caroline Laurendeau, Isabelle Bureau, Jean-FranÃois Ricci, Christophe Gerbeau, Gaelle Fossard, Mael Heiblig, Stephane Bouee
Journal: Blood (2014)
Perspectives in immunotherapy: meeting report from the “Immunotherapy Bridge”, Napoli, December 5th 2015
Authors: Paolo A. Ascierto, Maria Libera Ascierto, Silvia Formenti, Sacha Gnjatic, Hans Hammers, Vera Hirsh, Rolf Kiessling, Ignacio Melero, Rita Nanda, Graham Pawelec, Sandro Pignata, Pedro Romero, Daniel E. Speiser, Bernard A. Fox, Francesco M. Marincola
Journal: Journal for ImmunoTherapy of Cancer (2016)

Harnessing the immune system and preventing immune escape, the immunotherapy of cancer provides great potential for clinical application, in broad patient populations, achieving both conventional and unconventional clinical responses. After the substantial advances in melanoma, the focus of cancer immunotherapy has expanded to include many other cancers. Targeting immune checkpoints and further mechanisms used by tumors to avoid anticancer immunity, different approaches are under evaluation, including combination therapies. The first Immunotherapy Bridge meeting focused on various cancer types including melanoma, non-small cell lung cancer, renal cell, breast and ovarian carcinoma, and discussed mechanisms of action of single agents and combination strategies, and the prediction of clinical responses.
Temozolomide (TMZ) maintenance in patients with primary brain cancer treated with postoperative TMZ plus radiotherapy (RT): A retrospective analysis.
Authors: Luca Moscetti, Maria Agnese Fabbri, Isabella Sperduti, Giovanni Mansueto, Anna Maria Fariello, Teresa Gamucci, Michle Battista, Massimiliano Loffreda, Luciano Pompei, Enzo Ruggeri
Journal: Journal of Clinical Oncology (2012)

e12514 Background: A systematic review of patients affected with primary brain cancer treated with post-operative TMZ+RT and TMZ maintenance was undertaken in order to evaluate the efficacy and toxicity in an unselected population. Methods: Ninety-nine patients were detected. Main characteristics were: median age 62 years (range 28-80); M/F: 58/41; PS 0/1: 92 pts; complete resection: 20; subtotal resection: 75, biopsy only: 4. The median RT dose delivered was 60 Gy (range 40-60 Gy). All the 99 pts received TMZ at 75 mg/m 2 concomitantly to RT. Maintenance therapy with TMZ was given to non progressive pts, starting 6 weeks after chemoradiation, at the dose of 150 mg/m 2 for the 1 st cycle and 200 mg/m 2 q 4 weeks d. 1-5 for subsequent cycles and continued until disease progression or intolerance. Results: Patients with evaluable disease (n=79 pts) had an overall response rate of 16% (12 partial response and 1 complete response), while a stable disease was observed in 49/79 pts (62%). Maintenance TMZ was given to 77/99 pts (78%). Hematologic toxicities (CTCAE v.3) include: Gr. 3/4 neutropenia (4%), febrile neutropenia (1%), Gr. 3/4 thrombocytopenia (13%), Gr. 3 anemia (1%). One pt developed a bone marrow aplasia and another one a Steven-Johnson syndrome recovered after high supportive treatment. Toxicities caused discontinuation of TMZ in 9 patients (11%). At 2-yrs, at both univariate and multivariate analysis, a significant improvement in progression-free survival (PFS) and in overall survival (OS) was observed in pts completely resected and in pts achieving a response or a stable disease &gt;6 months. In pts achieving a response and in pts completely resected the HR for the 2-yrs PFS was 0.06 (95%CI 0.03-0.11, p&lt;0.0001) and 0.02 (95%CI 0.01-0.04, p&lt;0.0001), respectively. For the 2-yrs OS the HR was 0.08 (95%CI 0.04-0.16, p&lt;0.001) and 0.02 (95%CI 0.01-0.06, p&lt;0.0001). No difference was observed for sex, age, PS and histology. Conclusions: Complete resection, response or prolonged stabilization to maintenance TMZ are factors associated with a statistically improvement in OS and PFS.
A randomized, phase IIb study of sunitinib plus 5-fluorouracil, leucovorin, and oxaliplatin (mFOLFOX6) versus bevacizumab plus mFOLFOX6 as first-line treatment for metastatic colorectal cancer (mCRC): Interim results.
Authors: J. R. Hecht, T. Yoshino, E. P. Mitchell, M. S. Dees, A. M. Countouriotis, E. C. Maneval, A. Kretzschmar
Journal: Journal of Clinical Oncology (2010)

3532 Background: Studies with bevacizumab have shown the benefits of targeting vascular endothelial growth factor in mCRC patients (pts). The oral tyrosine kinase inhibitor sunitinib inhibits multiple angiogenic targets, including VEGF receptors, which may translate into increased antitumor activity relative to single-targeted agents. Methods: This phase IIb open-label study enrolled pts with previously untreated mCRC in the US, Germany, Japan, and Denmark. Pts were stratified by performance status, baseline LDH, and prior adjuvant treatment, and randomized 1:1 to sunitinib 37.5 mg/day 4 wks on, 2 wks off (4/2) with mFOLFOX6 q2w (Arm A), or bevacizumab 5 mg/kg q2w with mFOLFOX6 q2w (Arm B). The primary endpoint was progression-free survival (PFS). Secondary endpoints included objective response rate (ORR), safety, and quality of life. Tumor assessments were performed every 8 wks. Results: The study was closed to enrollment on 23 Nov 2009 after accruing 191 pts, randomized to Arm A (n=96) or Arm B (n=95). Thus far, among 167 patients who had the opportunity for at least 2 on-study tumor assessments, antitumor activity appears similar between the arms as shown below. Median treatment duration was 4 months (range 0-13) for Arm A and 5 months (range 0-15) for Arm B. Toxicities were more common in Arm A as 36% of pts required at least 1 dose reduction vs. 10% in Arm B, primarily due to neutropenia and thrombocytopenia. Disease progression (19% A, 13% B) was the main reason for pt withdrawal. The most frequently reported grade 3/4 AEs were fatigue (11% A, 5% B) and diarrhea (7% A, 5% B). 4% of pts in Arm A also experienced febrile neutropenia. Median PFS and OS have not been reached at this time. Conclusions: Sunitinib (starting dose 37.5 mg 4/2) in combination with mFOLFOX6 appears to be safe in mCRC pts although dose reductions were required in about 1/3 of pts. Initial results show similar antitumor activity as compared to bevacizumab + mFOLFOX6. Updated efficacy, safety, and patient-reported outcomes will be reported. Best response, n (%) Arm A, n = 85 Arm B, n = 82 CR 0 1 (1) PR 36 (42) 31 (38) SD 36 (42) 41 (50) PD 6 (7) 3 (4) Not evaluable 7 (8) 6 (7) Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Pfizer Pfizer Pfizer Pfizer
THE POSITIVE ASSOCIATION BETWEEN BREAST TUMOR SIZE AND LYMPH NODE INVOLVEMENT IN LOBULAR BREAST CANCERS IS PROGESTERONE RECEPTOR DEPENDENT
Authors: Thijs Vandorpe, I Dierickx, Hans Wildiers, Anne-Sophie Dieudonné, Ben Van Calster, Robert Paridaens, P Moerman, Ann Smeets, Rose Christiaens, Patrick Neven
Journal: Annals of Oncology (2010)
Safe handling of oral chemotherapeutic agents in clinical practice at Saudi hospitals.
Authors: Nagwa Abdel Rahman Ibrahim, Ashraf Al Alwan, Ahmed Al Eid, Mona Al Onazi, Meznah Al Mutairi
Journal: Journal of Clinical Oncology (2015)

e17752 Background: Chemotherapeutic agents are defined by OSHA as hazardous drugs and require special precautions in handling to minimize short and long term effects. These agents are available in different dosage forms as intravenous, injectable and oral form. There is a widespread use of oral chemotherapy as it is associated with ease administration and has the same risk of exposure compared to intravenous form. There is a misconception that exposure risk to oral chemotherapy is less and it is safer to handle. In this study we aim to asses the knowledge of health care professionals including pharmacists, pharmacy technicians and nurses, about safe handling oral chemotherapeutic agents in clinical practice. Methods: A cross – sectional descriptive multi-center study using structured questionnaire was conducted between July and November 2014. The survey consists of five sections including demographic data, handling, storage, administration and disposal practice. Survey responses were analyzed using descriptive statistics including univariate and multivariate analyses. Results: We collected a total of 1000 survey from 4 hospitals in Riyadh, Saudi Arabia. The ratio of males to females participants was 411/589 (41.1%/58.9%). Most of the surveys completed by pharmacists (52.6%), years of experience for majority of participants were located between 2-5 years (36.8%), work location was mostly in-patient pharmacy (42%). The highest percentage of wrong answers was located under the handling section; mainly the question about the risk of harm of oral chemotherapy compared to intravenous dosage form, (60%) of the participants had a wrong answer for this question. The univariate analysis revealed that position; years of experience and work location are predictors of best practice of safe handling of oral chemotherapeutic agents which remained significant in the multivariate analysis. Conclusions: Results of this study revealed the high demand to improve health care professional’s knowledge about safe handling of oral chemotherapeutic agents. Conduction of awareness and educational programs are top priority to ensure safety.