tbuckley/cabot-search huggingface dataset:
The combination of capecitabine and cyclophosphamide for metastatic breast cancer patients
Authors: M. Suzuki, I. Kimijima, M. Ishii
Journal: Journal of Clinical Oncology (2009)

e12025 Background: Capecitabine (X) is converted into 5-FU by thymidine phospholylase (TP). Cyclophosphamide (C) has been shown to make TP higher in the preclinical study. Therefore, the combination of capecitabine and cyclophosphamide (XC) is thought to have a synergistic activity. We explored the efficacy of XC for metastatic breast cancer patients. Methods: 50 metastatic breast cancer patients were treated with XC in our medical center between April 2004 and December 2008. Median patient age was 58 years old (range: 34–79 years old). 36 patients were postmenopausal. X was 1675mg/m2 days 1–21 and C was 67mg/m2 days 1–14 on a 28-day cycle in all-oral combination. This therapy was continued until progression of disease or unacceptable toxicities occurring. Results: Median time to treatment failure was 28 weeks (range: 2–158 weeks). 9 patients were not evaluable for tumor response. Among 41 evaluable patients, complete response (CR) was observed in 2.4% (1 patient) and partial response (PR) was 29.2% (12 patients). Stable disease (SD) was 41.4% (17 patients) and progression of the disease (PD) was 26.8% (11 patients). The objective response rate (CR+PR) was 31.7% and the overall clinical benefit (CR+PR+SDÅÜ24 weeks) was 53.6%. Significant toxicities were uncommon: grade 3 toxicities were encountered for neutropenia in 1 patient, anorexia in 1 patient and hand-foot syndrome in 2 patients. Conclusions: XC is an effective regimen in metastatic breast cancer, and this therapy is of an easy administration and very well tolerated. No significant financial relationships to disclose.
Detection of potential actionable targets in appendiceal cancer detected by immunohistochemistry (IHC), fluorescent in situ hybridization (FISH), and mutational analysis.
Authors: Erkut Borazanci, Jeffery Kimbrough, Jasgit C. Sachdev, Sherri Z. Millis, Samuel Ejadi, Ken Burnett, Stephanie Ratliff, Daniel D. Von Hoff, Ramesh K. Ramanathan
Journal: Journal of Clinical Oncology (2014)

469 Background: Appendiceal cancers are rare and there are no established guidelines for adjuvant treatment and metastatic disease. Methods: Samples were identified from &gt; 60,000 global tumors analyzed at a referral molecular profiling CLIA certified laboratory (Caris Life Sciences) for biomarkers of drug sensitivity, under an approved protocol. 285 samples with primary tumor sites of appendix were identified (M/F ratio of 38%/62%; mean age of 55). Approximately 80% of samples were adenocarcinomas, 10% carcinoids, and 10% of indeterminate histology. IHC assays (n=273) were performed with up to 30 biomarkers; FISH (n=39) for c-Myc, cMET, EGFR, HER2 and/or TOPO2A gene copy amplifications; and sequencing done ( n= 223) for KRAS, EGFR, PIK3CA, and BRAF. Results: Targets on IHC: 97% high BCRP; 16% high KIT; 80% high COX-2; 50%high EGFR; 30% low MGMT, 81% high MRP1, 35% high PDGFR, 82% low PTEN, 27% high RRM1, 39% high SPARC; 67% high TLE3, 27% high TOPO2A ; 63% high TOPOI, and 99% negative TS. Targets on FISH: 5% amplified EGFR and 0% amplified Her2/Neu. Sequencing results: 53% mutated KRAS and 2% mutated BRAF. Conclusions: The high levels of drug resistance proteins (BCRP and MRP1) highlights the difficulty in treating these tumors. The incidence of KRAS mutations (53%) and low expression of TS (99%) is noteworthy, and points towards using 5FU/capecitabine as a backbone of therapy. Therapeutic options are varied and options include TOPO1 inhibitors (irinotecan/topotecan), EGFR inhibitors (erlotinib, cetuximab), PDGFR antagonists (regorafenib, axitinib), MGMT (temazolamide), BRAF inhibitors (vemurafenib, dabrafenib) and SPARC (nab-paclitaxel). These findings indicate the need to evaluate patient samples for patterns in marker expression and alteration, in order to better understand the molecular biology and formulate a personalized therapy approach in these difficult to treat cancers, and to pursue whole genomic sequencing. Supported by a grant from Caris Life Sciences.
Elective chemotherapy admission pilot and work-flow improvements to reduce excess days.
Authors: Wendy Rowehl Miano, Paula Silverman, Frank Colella, Bernadette McQuigg, Heather Hines, Santina Ciarallo, Lalena Whittington, Sarah Belcher
Journal: Journal of Clinical Oncology (2012)

101 Background: The Inpatient (Inpt) Oncology Service at University Hospitals Seidman Cancer Center, a large urban academic NCI Comprehensive Cancer Center was charged with identifying opportunities to link patient (pt) quality improvement and decreased length of stay (LOS) in pts admitted for elective chemotherapy (EC). Historically, EC admissions were delayed due to pt variables, inpt bed availability, and chemotherapy order entry errors. Often chemotherapy was not initiated until late evening on day of admission, resulting in increased LOS. Safety concerns associated with late starts included fewer pharmacy resources, lower nurse/pt ratio, and no onsite APRN. Methods: A 2-month pilot was conducted, using an intervention group (IG) and control (C) group representing usual care (UC). The IG group was a subset with oropharyngeal pts and C group, all other EC admissions. Pre-registration and bed placement processes were reviewed. Workflow changes for IG included chemotherapy order set entered in electronic medical record 48 hours before admission, labs drawn day before admission, and weekly huddle including admitting, inpt and outpatient (Outpt) teams to review upcoming week’s admissions. IG pts were pre-scheduled for am admission. Inpt oncology services incorporated admissions into morning workflow. Census was taken above cap to accommodate IG patients. Time parameters were tracked from point of pt arrival in Admitting to initiation of EC. Results: There were 32 pts in the 2-month pilot study; 14 in the IG and 9 in UC. Mean admit time was 0900 (range 0730-1030) for IG and 1200 noon (range 1000-1600) for UC. Initiation of EC before 1500 occurred in 93% of IG compared to 11% of UC pts. This resulted in an average decreased LOS for IG of 1.1 day compared to UC. Pt and family comments included appreciation of predictable admit time and LOS. Conclusions: Because of the 8-week pilot success, these EC workflow changes have been implemented across Oncology services. Weekly huddles and coordination of clinical services across inpt and outpt settings continue to show advantage of proactive planning and troubleshooting before the day of EC admission. More importantly, EC pt safety and experience has improved with these work-flow changes.
Second-line erlotinib in patients with advanced non-small-cell lung cancer (NSCLC): Results from a large, open-label study
Authors: L. Crinò, M. Boyer, W. E. Eberhardt, Z. Balikó, E. F. Smit
Journal: Journal of Clinical Oncology (2008)

19002 Background: Erlotinib improves survival, symptom control and quality of life for patients (pts) with advanced NSCLC (Shepherd et al, N Engl J Med 2005;353:123–32). Overall survival (OS) for 2nd-line pts with PS 0/1 appears to be equivalent for erlotinib (9.4 mo), docetaxel (9.1 mo) and pemetrexed (9.4mo) (Shepherd et al, 2005; Shepherd et al, J Clin Oncol 2000;18:2095–103; Hanna et al, J Clin Oncol 2004;22:1589–97). Methods: Pts with stage IIIB/IV NSCLC who had previously failed on or were unsuitable for chemo-/radiotherapy were recruited into the non-randomized, open-label TRUST study, and received erlotinib 150mg/d p.o. until disease progression or unacceptable toxicity. Results: Data cut-off was October 25, 2007; data are presented here for 3290 pts (2535 PS 0/1) who received erlotinib as 2nd line. Median age was 62 yrs (range: 19–92 yrs) and baseline characteristics (%) include: male/female = 60/40; Caucasian/Oriental/other = 70/22/8; stage IIIB/IV = 23/77; adenocarcinoma/squamous-cell/other = 56/23/21. Best response data were available for 2724 pts: 23 (<1%) had a CR, 357 (13%) had a PR and 1482 (54%) had SD. Disease control rate (CR+PR+SD) was 68% in all pts and 69% in those with PS 0/1. Median PFS was 13.7 wks in all pts, 15.6 wks for those of PS 0/1, 9.6 wks in PS 2 pts and 8.3 wks in PS 3 pts. Pts with rash of any grade had a significantly longer median PFS than those without rash (17.9 wks vs 8.1 wks; p<0.0001). OS data are not yet mature (>25% censored) but will be reported. Analysis of safety data found no new safety signals; only 123 pts (4%) in this subgroup reported an erlotinib-related serious adverse event (SAE) and none of the individual SAEs reported occurred in ≥1% of pts. Erlotinib-related rash was reported in 71% of pts; 84% of these cases were gr 1/2. Conclusions: In this large group of pts treated 2nd-line, erlotinib was associated with efficacy outcomes equivalent to those observed in the pivotal phase III BR.21 trial. Pts with good PS (0/1) had improved outcomes compared with pts of PS 2/3. Erlotinib has a favorable toxicity profile, making it a good alternative for NSCLC in the 2nd-line setting. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration AstraZeneca, Bristol-Myers, Eli Lilly, Novartis, OSI, Pfizer, Roche AstraZeneca, Bristol-Myers, Eli Lilly, Novartis, Pfizer, Pierre Fabre, Roche
Final results of a phase II clinical and pharmacokinetical trial with oral idarubicin (IDA) in elderly patients (pts) with metastatic breast cancer (MBC)
Authors: D. Crivellari, D. Lombardi, R. Sorio, N. La Mura, C. Massacesi, A. Lucenti, A. Ferro, A. Veronesi, G. Corona, G. Toffoli
Journal: Journal of Clinical Oncology (2005)

727 Background: Anthracyclines are among the most active agents in the treatment of MBC. There is a concern in their use in elderly pts due to possible cardiotoxicity Methods: Pts with MBC, measurable or evaluable lesions, aged 65 or more, PS 0–2, no prior anthracyclines, were treated with IDA initially 7.5 mg/day and after the first 14 pts with 5 mg/day for 21 consecutive days q 4 weeks. The primary aim of the study was the evaluation of activity and tolerability, secondary aim was to correlate the toxicity profile with the plasmatic pharmacokinetics of the metabolite. IDA and IDOL plasma concentrations were investigated on day 0, 7, 14, 21. Results: Between April 1999 and June 2004, 47 pts (14 treated with 7.5 mg and 33 treated with 5 mg/day) were accrued. Median age was 74 and 75 years respectively. Visceral involvement was present in 18/33 (55%). Median number of metastatic sites was 1. Toxicity was low with 5 mg/day (neutropenia grade 4 in 6%). Alopecia grade > 1 and cardiotoxicity did not occur. The table below gives the results of the overall study. IDA and IDOL plasma levels will be presented. Median TTP was 6.7 months, median OS was 22.5 months. Conclusions: This schedule of IDA is feasible and gives elderly pts an opportunity to be treated at home with an active drug whose main toxicity is neutropenia. No significant financial relationships to disclose.
A phase I dose-escalation study to evaluate GDC-0941, a pan-PI3K inhibitor, administered QD or BID in patients with advanced or metastatic solid tumors.
Authors: D. D. Von Hoff, P. LoRusso, G. D. Demetri, G. J. Weiss, G. Shapiro, R. K. Ramanathan, J. A. Ware, R. Raja, J. Jin, G. G. Levy, K. E. Mazina, A. J. Wagner
Journal: Journal of Clinical Oncology (2011)

3052^ Background: The PI3K-PTEN-AKT signaling pathway is deregulated in a wide variety of cancers. GDC-0941 is a potent, oral, selective pan-inhibitor of class I PI3K with IC50 against the isoforms of p110 ranging from 3 nM (p110α) to 75 nM (p110γ) in vitro. Methods: A 2-stage phase I dose-escalation study (GDC4255g) using a 3+3 design was initiated in patients (pts) with solid tumors to evaluate the pharmacokinetic (PK), pharmacodynamic (PD), and safety of GDC-0941. Stage 2 is an expansion phase at MTD enrolling pts with solid tumors and pts with PIK3CA mutant (mt) breast cancer. GDC-0941 was given on Day 1, followed by a 1-week (wk) washout for single-dose PK and PD markers. GDC-0941 was then dosed QD or BID on a 21/28 schedule. Archival tissue was assayed for PI3K mt/amplification and PTEN status. Results: Forty-nine pts were enrolled in 12 cohorts (15-450 mg) in the QD arm. Thirty-six pts have been enrolled in 8 cohorts in the BID arm at total daily doses (TDD) from 60-450 mg. The MTD was exceeded at 450 mg with dose limiting toxicities (DLT) of grade (Gr) 3 macular rash and Gr 3 asymptomatic T-wave inversion on ECG in the QD arm and Gr 3 thrombocytopenia and Gr 4 hyperglycemia in the BID arm. Other significant drug-related AEs at 450 mg were Gr 3 increased ALT and AST in the BID arm and Gr 3 fatigue in the QD arm. Drug-related AEs reported in ³10% of pts were similar in both arms with nausea, diarrhea, vomiting, fatigue, decreased appetite, dysgeusia, and rash. Two patients have exhibited partial responses (PR) by RECIST: an endocervical cancer (PIK3CA mt E545K) pt treated at 330 mg TDD in the BID arm who also had a 80% decrease in tumor FDG avidity by PET scan and continues on-study > 8 mo and an ER+, HER2- breast cancer pt treated at 130 mg QD who was on-study for ~5 mo. Additional signs of anti-tumor activity include CA-125 responses in 3 pts with ovarian cancer; one with known high PIK3CA gene copy number who was on-study for 15 mo and had a 23% decrease in target lesion by RECIST. Conclusions: GDC-0941 is generally well tolerated administered either QD or BID at doses below 450 mg with similar PK exposures and safety profiles. Clinical activity was observed below 450 mg with 2 PRs by RECIST.
Analysis of interleukin 10 (IL-10) -1082G/A single nucleotide polymorphism (SNP) genotypes in breast cancer (BC) patients (pts) and in &gt;95 years old cancer free women
Authors: S. Palmeri, D. Lio, M. Vaglica, A. Crivello, E. Vassallo, G. I. Forte, M. C. Macaluso, C. Raimondi, A. Accardo, C. Caruso
Journal: Journal of Clinical Oncology (2005)

9656 Background:the anti-inflammatory IL-10 -1082 (G/A) SNP might be associated with different risk for breast tumor development. The -1082GG homozygous genotype is associated with an higher IL-10 production compared to 1082GA or AA genotypes. Cancer rates increase sharply with age.The incidence and mortality for cancer show a levelling off around 85–90 years of age, followed by a plateau, or even a decline in the last decades of life. Methods: we studied 86 consecutive BC pts (26 Stage I, 37 II, 9 III,14 IV; median age 60), 162 healthy age matched (CTRL) and 40 >95 years old women (>95 CTRL).All pts, after a written informed consent. were genotyped for the IL-10 - 1082 G/A SNPs, using amplification refractory mutation system polymerase chain reaction (ARMS-PCR). Results: data are reported in the table.BC pts showed the lowest frequency of anti-inflammatory -1082GG genotype compared to age matched and oldest controls. -1082 GG, GA and AA frequencies were significantly different between patient and >95 years old control group (χ2 test with Yate’s correction= 6.21; p= 0.045). Conclusions:these data are in agreement with recent reports on the association of pro-inflammatory cytokine gene background and BC. Our data showed an opposite genetic profile of this specific IL-10 polymorphism in BC and in >95 years old subjects and thus there is a suggestion that some IL-10 polymorphisms may be considered a risk factor for BC. Moreover it seems reasonable to speculate that centenarians are people endowed with a peculiar resistance to cancer. No significant financial relationships to disclose.
Quality-of-life assessment in patients with malignant ascites: Results of a multicenter phase II/III study comparing paracentesis plus catumaxomab with paracentesis alone.
Authors: A. Gonschior, M. M. Heiss, M. H. Moehler, S. L. Parsons, H. Gilet
Journal: Journal of Clinical Oncology (2011)

9113 Background: Patients with malignant ascites (MA) have a poor prognosis and therapeutic options are limited to palliative treatment. Quality of life (QoL) assessment is therefore of particular importance to demonstrate the value of a new treatment. The trifunctional antibody catumaxomab is approved for the treatment of MA. Following the demonstration of the superiority of paracentesis plus catumaxomab vs paracentesis alone, the objective of this analysis was to compare the time to first deterioration in QoL with paracentesis plus catumaxomab vs paracentesis alone (control). Methods: In a 2-arm, randomized (2:1), open-label, multicenter, phase II/III study in patients with symptomatic MA due to EpCAM-positive cancer, the EORTC QLQ-C30 was used to evaluate QoL at screening, months 1, 3, and 7, and repuncture. Time to first deterioration in QLQ-C30 scores was defined as decrease in the score of at least 5 points and compared between patients randomized to catumaxomab (N=160) and control (N=85), using survival methods with log-rank test and Cox models adjusted for baseline score, country, and primary tumor type. Sensitivity analyses were conducted with a definition of time to deterioration of at least a 10-point decrease in QLQ-C30 scores. Results: Deterioration in QoL scores appeared more rapidly in the control vs catumaxomab group. Between 7% and 35% of patients in the control group vs 0% and 14% in the catumaxomab group showed deterioration in QoL scores before 30 days. The difference in time to first deterioration in QoL between the groups was statistically significant for all QLQ-C30 scores (p<0.05). Results were confirmed using Cox models (p<0.05 for 14 of 15 scores) with hazard ratios ranging from 0.04 for appetite loss to 0.13 for constipation. Sensitivity analysis also resulted in statistically significant differences in favor of catumaxomab for most other scores. Conclusions: Deterioration of QoL was delayed by treatment with catumaxomab in patients suffering from MA. Compared with paracentesis alone, catumaxomab enabled patients to benefit from better QoL during a prolonged survival period.
Correlation of a novel whole blood RT-PCR assay measuring AR-V7 expression with outcomes in metastatic castration-resistant prostate cancer (mCRPC) patients treated with abiraterone acetate (ABI).
Authors: Tilman Todenhöfer, Arun Azad, Craig Stewart, Jian Gao, Bernhard J. Eigl, Peter C. Black, Anthony M. Joshua, Kim N. Chi
Journal: Journal of Clinical Oncology (2016)

223 Background: Expression of androgen receptor splice variant 7 (AR-V7) in circulating tumor cells (CTCs) has been associated with resistance to ABI and enzalutamide (ENZ) (Antonarakis et al. N Engl J Med 2014). We have developed a RT-PCR assay that is neither time sensitive nor requires CTC enrichment for detection of prostate cancer (PCa)-associated transcripts in whole blood. Using this assay, our aim was to correlate AR-V7 expression with outcomes on ABI. Methods: 2.5 ml whole blood was collected into PAXgene RNA tubes from mCRPC patients (pts) commencing ABI. RT-PCR was performed for the following genes: AR-V7, FOXA1, GRHL2, HOXB13, KLK2, KLK3 and TMPRSS2:ERG. For each gene, the highest CT value among 20 normal controls was set as the threshold for a positive (+) test. Clinical endpoints were PSA50 response rate (RR) (PSA decline ≥ 50% confirmed ≥ 3 weeks later), PSA30 RR, time to PSA (PCWG2 criteria) or clinical progression (change in anti-cancer therapy or decline in ECOG performance status (PS) ≥ 2 levels due to PCa), and overall survival (OS). Results: Whole blood samples were obtained from 37 pts. Median age was 70. 59% received prior docetaxel. All pts were ABI and ENZ naïve. PSA50 RR was 37% and PSA30 RR was 48%. Median progression-free survival (PFS) was 3.8 months (mos) and median OS was 21.0 mos. 11% (4/37) of pts were AR-V7+. AR-V7+ pts were more likely to have high ALP (P= 0.04; Χ 2 ), high LDH (P= 0.07) and ECOG PS ≥ 2 (P= 0.052). Pts with an AR-V7+ test had lower PSA50 RR (0% vs. 42%, P= 0.10; Χ 2 ) and PSA30 RR (0% vs. 52%, P= 0.051) together with shorter median PFS (0.7 mos vs. 4.0 mos, P&lt; 0.001; log-rank) and median OS (5.5 mos vs. 22.1 mos, P&lt; 0.001). Other factors linked with worse OS were high ALP (P= 0.02), liver metastases (P= 0.03), ≤ 36 mos on primary hormone therapy (P= 0.04), HOXB13+ (P= 0.03) and KLK2+ (P&lt; 0.001). Conclusions: RT-PCR detection of AR-V7 transcripts in whole blood was associated with a 0% PSA RR and significantly inferior PFS and OS in pts treated with ABI. These results reinforce the potential utility of AR-V7 as a prognostic and predictive biomarker for mCRPC. Validation of the assay in larger datasets is ongoing.
Caregiver symptom burden assessment using the Edmonton Symptom Assessment System (ESAS): A preliminary report.
Authors: Kimberson Tanco, Marieberta Vidal, Joseph Anthony Arthur, David Hui, Gary B. Chisholm, Eduardo Bruera
Journal: Journal of Clinical Oncology (2015)

227 Background: Regular assessment of caregiver symptom burden during patient visits would allow prompt referral for their care. The ESAS is a multidimensional tool used in patients but not caregivers. The objectives of this study were to determine the feasibility of the ESAS in assessing caregiver symptoms defined as completing 9/12 items, assess caregiver-reported usefulness of its completion, determine the association of symptom scores between patients, caregivers and various clinical and psychosocial factors, and determine concurrent validity with the Zarit Burden Interview-12 (ZBI-12). Methods: A prospective study of 90 patient-primary caregiver dyads in an outpatient Supportive Care Center in a cancer center was conducted. The 12 item ESAS-FS was completed by the dyads with other measures of clinical and psychosocial factors [demographics, cancer diagnosis, co-morbidities, caregiving activities, prognostic index and patient’s performance status]. Results: The ESAS is a feasible tool to assess caregiver symptom burden with 90/90 caregivers [100%] completing at least 9/12 items; 66/90 caregivers [73%] found ESAS useful to report their symptom burden. A significant association was found between ESAS scores of caregivers and patients in depression [p &lt; 0.01], psychosocial items [depression, anxiety, well-being, financial distress, spiritual pain; p &lt; 0.01], and total symptom distress scores [p &lt; 0.01]. Caregiver employment status [p = 0.03] and total caregiver activities [p = 0.04] were significantly associated with total caregiver ESAS scores. There was no significant association between patient and caregiver co-morbidities [p = 0.08], prognostic index [0.07] and performance status [p = 0.26] to total caregiver ESAS scores. Caregivers recommended certain physical symptoms such as pain and nausea may be eliminated. Concurrent validity with ZBI-12 was not achieved [r = 0.53, p = 0.74] suggesting that ESAS measured different caregiver dimensions. Conclusions: The ESAS is a feasible tool to measure caregiver symptoms and was found useful by caregivers. Further research is needed to modify the ESAS based on caregiver’s recommendations and further psychometric studies need to be conducted.