tbuckley/cabot-search huggingface dataset:
Critical conversations in gynecologic oncology: Pilot study of communication skills training for fellows and advanced practice providers.
Authors: Carolyn Lefkowits, Kerri S. Bevis, Elise Carey, Robert Arnold, Lisa Podgurski
Journal: Journal of Clinical Oncology (2016)

29 Background: Good communication is crucial to good patient care. Gynecologic oncology providers often face challenging communication scenarios, including giving serious news and discussing goals of care. Communication skills training (CST) has been shown to improve skill acquisition among providers of multiple specialties, but it has not been described in providers from gynecologic oncology or any surgical oncology specialty. Methods: We conducted a two-day CST workshop, based on the VitalTalk© model, with four faculty members (2 gynecologic oncologists and 2 palliative care physicians) and 10 gynecologic oncology provider participants (5 fellows and 5 advanced practice providers). Using didactics, demonstrations and practice sessions with simulated patients we focused on giving serious news and discussing goals of care. Pre and immediate post-workshop surveys evaluated acceptability of the workshop, perceived impact of preparedness to address challenging communication scenarios and anticipated impact on clinical practice. We compared pre and post-workshop prevalence of score of 4 or 5 out of 5 on a Likert scale for preparedness to handle 14 challenging communication scenarios. Results: Participants reported statistically significant increase in preparedness to handle 13 out of 14 challenging communication scenarios. Among those 13 topics, magnitude of improvement in proportion of participants rating preparedness 4 or 5 out of 5 ranged from 40-100% (all p &lt; 0.05). All participants would recommend the course to others and all strongly agreed that this training should be required of all gynecologic oncology clinicians. Conclusions: Participants felt strongly that the workshop provided high quality education relevant to their practice. As a result of the workshop, participants reported statistically significantly increased preparedness to handle challenging communication scenarios. CST is feasible and has high perceived effectiveness for clinicians in the primarily surgical oncologic specialty of gynecologic oncology.
Enzalutamide in men with prostate cancer resistant to docetaxel and abiraterone.
Authors: Mark Creamer Scholz, Richard Y. Lam, Jeffrey S. Turner, Khang N. Chau, Lauren K. Becker, Clifford U. Felarca
Journal: Journal of Clinical Oncology (2014)

247 Background: Since FDA approval in 2011, abiraterone (Zytiga) has supplanted docetaxel as preferred first-line treatment for metastatic castrate-resistant prostate cancer. In August 2012 enzalutamide (Xtandi) was FDA-approved for the treatment of castrate-resistant prostate cancer after docetaxel (Taxotere). We performed a retrospective chart review at a large medical oncology clinic specializing in prostate cancer to determine the PSA response rates of enzalutamide administered to men who had previously progressed on both abiraterone and docetaxel. This report includes some patients who participated in the Astellas/Medivation-sponsored Early Access Program; however, it represents the author’s independent clinical experience. Methods: Enzalutamide was administered at a dose of 160 mg daily. Patients were subsequently followed with monthly physical examination, PSA and routine blood tests. No hepatotoxicity or seizures occurred. Men were considered evaluable for PSA response if they received enzalutamide for twelve weeks. A PSA decline of 30% from baseline after 12 weeks was defined as a response. A PSA increase of 30% from baseline within 12 weeks was defined as disease progression. Men with neither a 30% increase nor a 30% decline were classified as having stable disease. Results: 66 men were treated and 63 were evaluable for PSA response. Median age was 67. Median baseline PSA was 68.5. All participants had disease that had progressed on abiraterone. 55 men received previous docetaxel. 38 had received previous Provenge. Two men stopped before 12 weeks because of intolerable fatigue. One man died of progressive disease before 12 weeks. After a median follow up of 12.5 weeks, 18(29%) men met criteria for PSA response. 13(21%) men had stable disease and 32(51%) men had PSA progression. Conclusions: Enzalutamide has activity in a heavily pretreated population of men resistant to abiraterone and docetaxel.
Sorafenib (S) plus gemcitabine (GEM) and capecitabine (CAP) for advanced renal cell carcinoma (RCC): Updated phase I results from a phase I/II trial (NCI 6981)
Authors: S. Jeske, S. T. Tagawa, M. I. Milowsky, D. Matulich, S. Kung, M. W. Sung, D. Lehrer, J. Kaplan, D. M. Nanus
Journal: Journal of Clinical Oncology (2008)

16023 Background: While RCC is often considered chemo-resistant, the combination of GEM and 5-FU or CAP has activity. S improves progression free survival and is well-tolerated, but has limited response rates and patients (pts) progress at a median of 6 months. We chose to study the combination of S plus GEM and CAP. Methods: Cohorts of 3–6 pts were treated with S, GEM and CAP to establish dose limiting toxicity (DLT) and the maximum tolerated dose (MTD). After 2 of the initial 4 pts developed DLT (grade 3 hand/foot), the protocol was amended and the initial CAP dose was lowered. A subsequent amendment allowed one prior anti-angiogenic therapy. Results: 15 pts (median age 56) were enrolled with the following characteristics: 7 ECOG PS 0, 4 PS 1, 4 PS 2; 5 MSK good risk, 6 intermediate, and 4 poor risk; 14 of 15 clear cell variant (3 with sarcomatoid differentiation), 1 papillary variant; 40% with liver involvement and 40% with bone metastases; 13 pts were treatment naïve, 1 progressed on cytokines and 1 on sunitinib. Two of 5 pts experienced DLT at dose level B including one gr 3 ALT and one gr 3 mucositis. The MTD for the combination is S 200 mg/m2 BID d1–21, GEM 750 mg/m2 d1&8, and CAP 415 mg/m2 BID D1–14, with only 1 of 6 pts experiencing a DLT at this dose level (gr 3 hand/foot). Grade 3/4 toxicities were as follows: neutropenia 3 (20%), anemia 1, thrombocytopenia 1, hand/foot 3 (20%), fatigue 2 (13%), ALT 1, hypoalbuminemia 1, abdominal pain 1, pneumonia 1, proteinuria 1, thrombosis (catheter related) 1. Of 14 pts evaluable for response by RECIST, 4 with PR, 8 with SD, and 2 PD. Twelve of 14 had some improvement in measurable disease. 5 pts received at least 10 cycles; 4 phase I pts remain on therapy. Median progression free survival was 39.0 weeks [95% CI 20.2, 57.8] and median overall survival was 97.4 weeks [52.1, 142.8]. Conclusions: The combination of S plus GEM and CAP is tolerated with encouraging anti-tumor activity seen. The phase II component is open at the MTD to pts who have received up to 1 previous anti-angiogenic therapy and accrual is ongoing. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration Pfizer Pfizer, sanofi-aventis
First interim results of the global investigation of therapeutic decisions in hepatocellular carcinoma (HCC) and of its treatment with sorafenib (GIDEON) study: Use of sorafenib (Sor) by oncologists and nononcologists in the management of HCC.
Authors: A. P. Venook, R. Lencioni, J. A. Marrero, M. Kudo, K. Nakajima, S. Ye
Journal: Journal of Clinical Oncology (2011)

157 Background: GIDEON is an ongoing, global, prospective, non-interventional registry study of patients (pts) with unresectable HCC (uHCC) receiving Sor under real-life practice settings. From January 2009 to September 2010, over 2,200 pts have been enrolled from 32 countries. Per protocol, the first planned interim analysis was triggered when 500 enrolled pts were followed for at least 4 mos; the primary safety and efficacy results were reported in October 2010. A preplanned subset analysis of treatment patterns across MD specialities is reported here. Methods: Demographics, medical, disease and treatment history are recorded at enrolment; Sor dose, concomitant treatments, performance status, liver function are noted at follow-up. Standard efficacy measures and adverse events (AEs) are captured. Preplanned subanalysis by MD specialty was conducted. Results: Of the 141 treating MDs, 69 (49%) were hepatologists/gastroenterologists (Hep/GIs), 55 (39%) were medical oncologists (Oncs) and 17 (12%) were other specialties. Descriptive statistics of differences in pts' HCC stage, Sor treatment and AEs by the main specialties are shown for the 479 pts evaluable for safety (Table). Conclusions: Interim data from the GIDEON study suggests differential use of Sor by MD specialties. It appears that Oncs tend to treat with lower doses of Sor and for a somewhat shorter duration than Hep/GIs. If these data persist, it will be important to explore the reasons for these differences in Sor usage between Oncs and Hep/GIs and potential impact on patient outcomes. [Table: see text] No significant financial relationships to disclose.
Src pathway activation in RCC and the correlation with grade and survival and the development of a rational new target in RCC.
Authors: Chung-Han Lee, Martin Henner Voss, Roy Mano, Robert John Motzer, James Hsieh
Journal: Journal of Clinical Oncology (2014)

453 Background: Loss of the VHL tumor suppressor in clear cell renal cell carcinoma (ccRCC) leads to the accumulation of Hypoxia Inducible Factor (HIF) and aberrant transcription of downstream targets such as VEGF. Inhibition of VEGF is the underlying therapeutic principle of several approved targeted agents; however, other HIF transcriptional targets remain to be explored. Increased expression of the HIF transcriptional target CUB domain-containing protein 1 (CDCP1) is associated with poor survival in ccRCC. CDCP1 is a substrate and binding partner for Src-family tyrosine kinases (SFKs) and dictates substrate specificity. Crosstalk between the SFK signaling cascade and the HIF pathway may result in feed forward signal amplification. Upregulation of Src signaling increases HIF-dependent transcription by both VHL-dependent and -independent mechanisms. Reciprocally, HIF accumulation can activate Src through PDGFRα, focal adhesion kinase, and CDCP1. Methods: Data from The Cancer Genome Atlas (TCGA) was used to assess mRNA expression and protein phosphorylation as well as clinical parameters and outcome in patients with ccRCC. Correlations were analyzed via Mann-Whitney U-test. Survival data was obtained using the TCGA portal, and analyzed by logrank test. To investigate the therapeutic potential of Src inhibition, the IC50 of Dasatinib in primary tumors derived cell lines were determined by an AlamarBlue Assay. Results: Increased Src and CDCP1 mRNA expression and decreased phosphorylation on the Src inhibitory site Y527 correlated with increased Fuhrman grade. Decreased phosphorylation on the inhibitory site Y527 correlated with worse median overall survival (78.4 vs. 19.7 months, p&lt; 0.00001). Similarly, increased Src and CDCP1 mRNA expression correlated with worse overall survival (78.4 vs. 26.9 months, p &lt; 0.00001, 78.4 vs. 37.2 months, p = 0.005). In vitro inhibition of Src with Dasatinib induces growth inhibition of primary cell lines with sarcomatoid or rhabdoid features, histomorphologic criteria associated with higher grade disease and worse prognosis. Conclusions: The Src pathway might be biologically relevant for ccRCC, and Src inhibition may have therapeutic potential.
Assessing the quality of chemotherapy in an episode-based funding model in Ontario.
Authors: Leonard Kaizer, Vicky Simanovski, Huma Tariq, Carlin Lalonde, Irene Blais, William K. Evans
Journal: Journal of Clinical Oncology (2016)

1 Background: On April 1, 2014, the delivery of systemic treatment in Ontario transitioned to an episode-based funding model, which provides bundled payments for a full course of therapy delivered with adjuvant/curative intent and a monthly bundled payment for palliative intent. Disease Site Teams have defined treatment options and “best practice” for each funded adjuvant/curative regimen. Methods: The utilization of treatment according to disease and intent was analyzed for 35 systemic treatment facilities in Ontario, comparing actual practice (AP) with “best practice” (BP) (dose/schedule/cycle number), for common adjuvant/curative regimens. Variation in the choice of chemotherapy regimen was also reviewed. Results: Cases were included if they started a new course of adjuvant/curative therapy after January 1, 2014, and completed their treatment before July 31, 2015 (17,341 cases). For all disease sites and facilities, AP was equal to BP in 34.6% of cases, AP &lt; BP in 57.5%, and AP &gt; BP in 7.8% (Table). There was significant variation by disease site and facility. As a specific example, 1,368 courses of adjuvant mFOLFOX were completed for colorectal cancer: AP = BP (12 cycles) in 34% (range 7-70%), AP &lt; BP in 66% (range 30-93%), and AP &gt; BP in 1% (range 0-4%). Variation in choice of adjuvant regimen for breast cancer was also observed. Provincially, 21.5% of patients received non-anthracycline containing therapy, but the range in the 20 largest volume centers was 0% to 39.8%. Conclusions: With the administration of potentially curative therapy, it might be assumed that BP would be administered in the majority of cases. However, initial results demonstrate significant variation in practice in an episode based funding model. There is a need to understand the reasons for this variation and to identify potential opportunities to drive efficiency and to increase standardization by engaging clinical experts and practitioners. [Table: see text]
Cystatin C as a new covariate to predict the elimination of drugs: Application to carboplatin and topotecan
Authors: E. Chatelut, S. Séronie-Vivien, F. Thomas, A. Hoppe, J.-P. Delord, L. Gladieff, F. Dalenc, R. Bugat
Journal: Journal of Clinical Oncology (2005)

2029 Background: Individual dosing of drugs mainly eliminated by renal excretion is possible by estimation of the renal function. Most of the methods aim to assess the glomerular filtration rate using the creatinine clearance based on the serum creatinine level (SCr). Recently, serum cystatin C (cysC) has been proposed as an alternative endogenous marker of glomerular filtration rate. The purpose of this study was to assess cysC as a predictor of carboplatin and topotecan clearances (CL), drugs for which SCr was shown as a significant covariate to decrease the interindividual variability. Methods: Patients were receiving carboplatin (45 patients) or topotecan (59 patients) as part of established protocols. Their plasma concentrations versus time were analyzed according to a population pharmacokinetic approach using NONMEM program. Data-splitting was randomly done for both drugs to create a model building data set (for screening the relationships between morphologic, biological and demographic covariates and CL) and a model validation data set (for prospective evaluation of these relationships). Results: For carboplatin, the best covariate equation (± 95% Confidence Interval) was: CL (mL/min) = 110(±10.5). [ (SCr/75)−0.512(±0.255)]. [ (cysC/1.0)−0.327(±0.184)]. [ (BW/65)0.474(±0.223)]. [ (AGE/56)−0.387(±0.123)]. [0.854(± 0.099)SEX], with SCr in μmol/L, cysC in mg/L, BW (Body Weight) in kg, and SEX = 0 if male, =1 if female. This model was significantly better (p<0.02) than that without cysC. For topotecan, the best model included cysC and IBW (Ideal Body Weight) as covariates: CL (L/h) = 19.7(±1.3). (cysC/1.06)−0.61(±0.20). (IBW/57)0.93(± 0.58). This model had a significantly (p<0.01) better predictive value than that based on SCr and IBW. Conclusion: For both drugs, considering cysC results in a better clearance prediction than the current Methods: CysC needs further exploration as a promising covariate for drug dosing. No significant financial relationships to disclose.
Heterogeneity of intermediate prognosis patients (pts) with metastatic renal cell cancer (mRCC) treated with sunitinib.
Authors: Avishay Sella, M. Dror Michaelson, Ewa M. Matczak, Ronit Simantov, Mariajose Lechuga, Xun Lin, Robert A. Figlin
Journal: Journal of Clinical Oncology (2014)

446 Background: The Memorial Sloan Kettering Cancer Center risk model (MSKCC) stratifies pts with mRCC into 3 prognostic groups based on 5 risk factors. The Intermediate Prognosis (INTMP) risk group is characterized by the presence of 1 or 2 factors, equivalent to 15 possible distinct entities. This heterogeneity suggests that the efficacy of tyrosine kinase inhibitors may be less predictable in the INTMP than in the other groups. Methods: We identified 548 patients with INTMP mRCC from a pooled analysis of patients treated with sunitinib in 6 prospective phase II and III clinical trials. Statistical analysis was performed using Cox regression and Kaplan-Meier methods and Pearson chi-square tests. Results: Most INTMP pts were male (69%), with clear cell carcinoma (93%), good ECOG performance status (PS) (60.5% PS 0; 38% PS 1; 1.5% PS 2) and median age 60. There were 325 pts (56%) with 1risk factor, and the most common were &lt;1 year from diagnosis (38%); low hemoglobin (Hg) (29%), or both (16%). Objective response rate (RR) was 35.4%, progression free survival (PFS) was 8.4 months (m) and overall survival (OS) was 20.5 m. The 325 (59.3%) pts with one risk factor fared better than the 223 (40.7%) patients with two: PFS 10.7 vs 6.5 m, HR 0.684(95% CI 0.563-0.832, p&lt;0.001); OS 26.3 vs 14.1 m, HR 0.522 (95% CI 0.420-0.648, p&lt;0.001). RR was similar (38.5% vs 30.9%, p=0.071). Sunitinib was more effective in pts with PS 0: PFS 9.7 vs 7.8 m, HR 0.797 (95% CI 0.654-0.972, p=0.0242); OS 24.7 vs 14.0 m, HR 0.529 (95% CI 0.426-0.657, p&lt;0.001), RR 38.9% vs 30.1%, (p=0.036). The most common grade 3/4 adverse events (AE) were fatigue (17%), hypertension (10%), hand foot skin reaction (9%), and nausea (4%). Overall, 17% of patients discontinued due to AE, and the overall pattern of AEs did not vary among the subgroups. Conclusions: MSKCC INTMP is a heterogeneous group comprised mostly of pts with low Hg and/or &lt; 1 year from diagnosis. PFS and OS are superior in pts with 1 vs. 2 risk factors, and PS is also an important factor in the INTMP group. Sunitinib is active and well-tolerated in INTMP pts. Clinical trial information: NCT00077974, NCT00083889, NCT00137423, NCT00267748, NCT00338884, NCT00054886.
Comparing outcomes and toxicities from intensity-modulated radiation therapy and three-dimensional conformal radiation therapy for anal cancer: Is one really better?
Authors: Elisha T. Fredman, Aryavarta M. S. Kumar, May Abdel-Wahab
Journal: Journal of Clinical Oncology (2014)

589 Background: Intensity-modulated radiation therapy (IMRT) has largely supplanted 3-dimensional conformal radiation (3D-CRT) for definitive treatment of anal cancer due to its decreased toxicity and potentially improved outcomes. Convincing data directly demonstrating its advantages, however, remain limited. We compared outcomes, acute, and post-treatment toxicity of patients with anal cancer treated with concurrent chemotherapy and IMRT vs. 3D-CRT. Methods: We performed a single institution retrospective review of patients treated with IMRT or 3D-CRT as part of definitive Mitomycin-C/5-FU based chemoradiation for anal cancer from January 2003-December 2012. Results: 61 and 104 patients received IMRT and 3D-CRT respectively. Overall, 92.7% had squamous cell carcinoma. The mean pelvic dose before boost was 48.3Gy and 44Gy for IMRT and 3D-CRT respectively. Complete response, partial response, and disease progression rates were similar (83.6%, 8.2%, 8.2% for IMRT; 85.6%, 6.7%, 7.7% for 3D-CRT; p = ns). There was no significant difference in overall survival (p = 0.971), event free survival (p = 0.900), and local or distant recurrence rates (p = 0.118, p = 0.373). IMRT caused significantly less acute grade 1-2 incontinence (p = 0.035), grade 3-4 pain (p = 0.033) and fatigue (p = 0.030). Patients receiving IMRT had significantly fewer post-treatment toxicities (p = 0.008), outperforming 3D-CRT in 7/8 toxicities reviewed. Though total length of treatment was comparable between IMRT and 3D-CRT (43.6 and 44.5 days), the IMRT group had fewer, shorter treatment breaks (p = ns). Conclusions: This report represents the largest series directly comparing concurrent chemotherapy with IMRT vs. 3D-CRT for definitive treatment of anal cancer. IMRT significantly reduced acute and post-treatment toxicities and allowed for safe and effective pelvic dose escalation.
Phase I study of cediranib in combination with cisplatin plus fluoropyrimidine (S-1 or capecitabine) in Japanese patients (pts) with untreated advanced gastric cancer (AGC).
Authors: T. E. Nakajima, T. Satoh, K. Muro, Y. Yamada, Y. Shimada, D. Takahari, H. Hayashi, K. Taku, X. Shi, N. Boku
Journal: Journal of Clinical Oncology (2011)

111 Background: Cediranib (AZD2171) is an oral, highly potent inhibitor of VEGF signalling with activity versus all three VEGFRs and c-Kit. Combination therapy with cisplatin + oral fluoropyrimidine is commonly used as first-line treatment for AGC. This phase I study assessed cediranib in combination with cisplatin/S-1 or cisplatin/capecitabine in Japanese pts with previously untreated AGC. Methods: Eligible pts received cediranib 20 mg/day and either cisplatin 60 mg/m 2 iv, day 1 + S-1 40–60 mg bd, days 1–21, q5w (Arm A) or cisplatin 80 mg/m 2 iv, day 1 + capecitabine 1000 mg/m 2 bd, days 1–14, q3w (Arm B). The primary endpoint was safety and tolerability. Secondary endpoints included assessment of steady-state pharmacokinetics (PK) of cediranib and chemotherapy alone and in combination. Preliminary efficacy was an exploratory objective. Adverse events (AEs) were evaluated according to CTCAE v3.0. Results: Between Aug–Dec 2009, 14 pts (median age, 60.5 [27–72] years; male, n = 9; PS 0/1, n = 7/7) were recruited to Arm A (n = 6) or Arm B (n = 8). The safety profile in both arms was consistent with that of the individual agents. There were no unexpected toxicities. All pts experienced ≥1 AE. Dose-limiting toxicities were reported in 1 pt in Arm A (decreased appetite) and 1 pt in Arm B (decreased appetite, fatigue, hyponatremia). The most common AEs in Arm A were decreased appetite, fatigue, nausea, diarrhoea, decreased weight and neutropenia (all n = 5; 83%), and decreased appetite, fatigue, nausea (all n = 8; 100%) and constipation (n = 7; 88%) in Arm B. Five (83%) pts in Arm A and 6 (75%) in Arm B experienced grade ≥ 3 AEs. Grade 3 AEs in &gt; 1 pt were neutropenia (n = 3) in Arm A and hypokalaemia (n = 3), neutropenia, hyponatraemia and fatigue (all n = 2) in Arm B. Grade 4 syncope was reported in 1 pt in Arm A; this resolved on the same day it was observed. Preliminary efficacy and PK data will be presented. Conclusions: Cediranib 20 mg plus cisplatin/S-1 or cisplatin/capecitabine was generally well tolerated and considered suitable for further evaluation in pts with AGC. The safety profile of each regimen was comparable with the individual agents. No new toxicities were identified. [Table: see text]