tbuckley/cabot-search huggingface dataset:
Efficacy and safety of capecitabine plus oxaliplatin (XELOX) as the perioperative treatment of patients with potentially resectable liver-only metastases from colorectal cancer: A single arm, open-label, multicenter phase II trial (ML22298; NCT00997685).
Authors: Feng Lin, Guoxin Li, Zhonghua Chu, Chunyi Hao, Mingqing Chen, Zhiwei Jiang, Huanqiu Chen, Jianjiang Lin, Dechuan Li, Bing Hu, Xishan Wang
Journal: Journal of Clinical Oncology (2015)

777 Background: Surgical resection can improve survival of patients with resectable colorectal liver metastases (CLMs). Here, we investigatedthe efficacy and safety of XELOX as perioperative treatment for patients with potentially resectable CLM. Methods: Patients with potentially resectable liver-only metastases from CRC were enrolled. The primary endpoint of this study was progression-free survival (PFS); and the secondary endpoints included objective response rate (ORR), R0 resection rate, overall survival (OS) and safety profile of perioperative treatment of XELOX. Eligible patients were treated with XELOX (oxaliplatin 130 mg/m 2 on day 1 plus capecitabine 1,000 mg/m 2 b.i.d. for 14 days every 3 weeks). Tumor remission was assessed by CT after 6 weeks (2 cycles) of chemotherapy. Resectability of CLM was assessed by CT after 12 weeks (4 cycles) of chemotherapy. Adjuvant chemotherapy using XELOX was started within 8 weeks after hepatectomy. Results: Thirty patients (17 males and 13 females) were enrolled from 10 medical sites between January 2010 and October 2011, with median age of 57.5 years (range: 32-77). Median PFS was 336 days (95% CI: 173~385), and median OS was 912 days (95% CI: 516~1332). The ORR was 40% (12/30). The conversion rate from unresectable to resectable was 43.3% (13/30). Among these 11 patients who had received surgery (2 had withdrawn consent), 10 (90.9%) had received R0 resection. Subgroup analysis shows that patients who had received hepatectomy had longer median PFS [95% CI] (382 days [210~518] vs. 173 days [111~337], p = 0.0268) and median OS [95% CI] (1332 [721~NA] vs. 516 [295~1046], p = 0.005). There were 4 patients with post-operation complications of ascites and/or hydrothorax, and 3 patients had early chemotherapy termination due to drug-related AEs, including leukopenia, hepatotoxicity and diarrhea. Conclusions: Perioperative chemotherapy of XELOX is an option for patients with potentially resectable CLM due to the effect in prolonging PFS and OS, as well as the manageable toxicities and post-operation complications. Clinical trial information: NCT00997685.
Identification of localized rectal cancer (RC) patients (pts) who may not require preoperative (preop) chemoradiation (CRT).
Authors: D. Roda, M. Frasson, E. García-Granero, S. Roselló, B. Flor, E. Rodríguez, P. Esclapez, S. Campos, S. García-Botello, A. Cervantes-Ruiperez
Journal: Journal of Clinical Oncology (2010)

3512 Background: Preop CRT is becoming the standard of care for patients with locally advanced RC. However, since the introduction of total mesorectal excision (TME), local recurrence rates are significantly reduced and some pts can be spared from a potentially toxic overtreatment. Preop staging with magnetic resonance imaging (MRI) and/or endorectal ultrasonography (ERUS) may help in selecting pts for preop CRT. This retrospective study was designed to assess factors predicting recurrence in an institutional series of RC pts with clinical stage T2N+, T3N0/+, treated by radical surgery without preop CRT. Methods: Between Nov 1997 to Nov 2008, our multidisciplinary group staged preop 398 RC patients by ERUS and/or MRI. We selected for this analysis 154 consecutive pts, having uT2N+, uT3N0, and uT3N+ rc, who didn't get preop CRT. Macroscopical assessment of mesorectal excision and microscopic study of all circumferential resection margins (CRM) was determined. Factors potentially related with local recurrence (LR), Disease free survival (DFS) and overall survival (OS) were studied. Results: Median follow-up was 34 months (range, 18 to 68,2 months). LR rate was 8.5%, and 5-year DFS and OS were respectively 64.5% and 75.4% for the whole group. Threatened mesorectal fascia at preop staging, defined as tumor located at < 2 mm, was seen in 19 patients and was the most powerful single factor to predict a higher risk for LR, shorter DFS and worse OS. Other factors such as preop N+ or location of the tumor did not predict the risk of LR. Conclusions: Threatening of mesorectal fascia as defined preoperative by US or MRI, was the only significant factor predicting LR as well as worse DFS and OS. RC pts clinically staged as T3N0/+ or T2N+ > 2 mm away from mesorectal fascia could be treated with TME alone with a risk of LR of less than 5%, and overtreatment with preop CRT could be avoided. Differences in tumor-related events in threatened versus free mesorectal fascia % Events (threatened vs. free fascia) Hazard ratio 95% CI P value LR+ 21 vs. 4.5 7.2 1.9-27 0.004 DFS* 78.3 vs. 63.1 2.8 1.2-6.6 0.015 OS* 86.4 vs. 73.6 3.2 1.1-8.9 0.025 + Crude rate. * Actuarial rate at 5 years. No significant financial relationships to disclose.
Accelerated BEP for advanced germ cell tumors: An Australian multicenter phase I/II trial.
Authors: P. S. Grimison, D. B. Thomson, M. R. Stockler, M. D. Chatfield, M. Friedlander, V. Gebski, A. L. Boland, B. B. Houghton, H. Gurney, M. Rosenthal, N. Singhal, G. Kichenadasse, S. S. Wong, C. R. Lewis, P. A. Vasey, G. C. Toner
Journal: Journal of Clinical Oncology (2011)

4561 Background: Standard chemotherapy for advanced germ cell tumors is BEP (bleomycin, etoposide, cisplatin). 5-year survival is > 90% in good-risk disease, but only ~80% in intermediate and ~ 60% in poor risk disease. Accelerated (dose-dense) versions of standard regimens have proven more effective in other malignancies. We aimed to determine feasibility, tolerability and activity of an accelerated version of BEP. Methods: Single arm, multi-center, phase I/II trial (n=45 recruited). Target population was patients with advanced germ cell tumours and radiologically measurable disease. Patients with elevated serum tumour markers as only evidence of disease were ineligible. Treatment was cisplatin 20mg/m2 and etoposide 100mg/m2 on days 1-5, and pegylated G-CSF 6mg on day 6, all repeated every 2 weeks for 4 cycles (3 cycles for good risk). Bleomycin was given at 30kIU weekly to a total 12 doses (9 doses for good risk). Primary endpoint was regimen feasibility. Results: Results are presented for the 1st 41 patients enrolled from February 2008 to July 2010. 10 had poor risk disease (1 female), 15 intermediate risk, 16 good risk disease. Median follow-up is 14 months (range 2 to 27). At least 36 (88%) were eligible to start a 4th cycle of BEP on schedule or with no more than 1 week delay. Adverse events are presented in table 1. 22 of 41 patients (9 of 25 patients with intermediate or poor risk, 13 of 16 patients with good risk) achieved a complete response to chemotherapy +/- surgery. 4 of 41 patients have relapsed including one death. 1 year progression-free survival is 80% for intermediate or poor risk disease, and 100% for good risk disease. 1 year overall survival is 93% for intermediate or poor risk disease, and 100% for good risk disease. Conclusions: Feasibility and adverse events appears comparable to standard BEP. Efficacy data appears promising. Results from this trial and a similar study in the UK (Williams, ASCO 2008) provide the rationale for an international trial comparing accelerated versus standard versions of BEP. Number of patients with adverse events by CTCAE v3 criteria. G1/2 G3/4 Febrile neutropenia - 5 Other infection 7 6 Anemia 19 1 Nephrotoxicity 2 0 Neurotoxicity 19 0 Hearing loss 5 0 Tinnitus 30 0 Decrease in DLCO 38 0
A pilot study on the anticancer effects of novel candidate agent COH-SR4 in lung cancer.
Authors: David Berz
Journal: Journal of Clinical Oncology (2012)

28 Background: Non-small cell lung cancer is the leading cause of cancer deaths in the US. The success of current treatment strategies is limited by frequent aberrations in multiple signaling pathways. This includes loss-of-function mutations in the tumor suppressor p53 and activating mutations in multiple growth factor receptors, which converge to activate PI3K/Akt pathway. This calls for the development of novel, more active treatments. We investigated the anti-cancer effects of a novel compound called 1, 3 bis (3, 5-dichlorophenyl) urea (COH-SR4) in lung cancer. Methods: The anticancer effects of COH-SR4 were tested in p53-null H358 lung cancer cells. The antiproliferative effects were investigated in vitro by MTT assay. The bio-availability and antitumor effects were determined in vivo following the administration of 4 mg/kg of COH-SR4 to mice and H358-nu/nu nude mice xenografts. Results: The treatment with COH-SR4 resulted in effective inhibition of the proliferative potential of H358 lung cancer cells [IC 50 : 23+2 µM], effectively inducing apoptosis. The 4 mg/kg COH-SR4 administration resulted in a free serum concentration of 1+ 0.3 µM. Regression of established H358-xenografts was achieved without any overt toxicity. The histopathology of resected tumor sections revealed an increase in pAMPK (T 172 ) and a decrease in the nuclear proliferative marker Ki 67 and angiogenesis marker CD31. Western blot analyses of resected tumor lysates revealed a decrease in pAkt (S 473 ) and anti-apoptotic protein Bcl2 along with an increase in pAMPK (T 172 ), pro-apoptotic Bax and cleaved PARP levels. In addition, COH-SR4 lead to a decrease in the levels of the cell cycle regulators CDK4 and cyclin B1 as well as the mesenchymal marker vimentin, whilst increasing the epithelial marker E-cadherin. Conclusions: COH-SR4 represents a novel agent for the treatment of non small cell lung cancer. We demonstrated pronounced anti-proliferative and pro-apoptotic activity in vitro and in vivo as well as the capability to promote physiologic, epithelial differentiation. This implies not only therapeutic, but also preventive potential. Further studies are needed to establish the best possible clinical applications of COH-SR4 in lung cancer.
Netupitant/palonosetron (NEPA) for prevention of delayed chemotherapy-induced nausea and vomiting (CINV) in multiple cycles of chemotherapy.
Authors: Lee Steven Schwartzberg, Richard J. Gralla, Kimia Kashef, Hope Rugo
Journal: Journal of Clinical Oncology (2015)

211 Background: Prevention of CINV in the delayed phase (24-120 h post-chemotherapy) and over multiple cycles of chemotherapy remains a challenge. NEPA, a fixed combination of the NK 1 receptor antagonist (RA) netupitant (300 mg) and the 5-HT 3 RA palonosetron (PALO; 0.5 mg), has demonstrated efficacy in multiple studies, in both acute and delayed phases, during the first cycle of moderately or highly emetogenic chemotherapy (MEC and HEC, respectively) regimens. Two clinical trials evaluated NEPA over multiple cycles of chemotherapy. We report data for the delayed phase for each cycle. Methods: Both studies were Phase 3, double-blind, active-controlled studies. In study 1 (MEC), patients were randomized 1:1 to receive a single oral dose of NEPA (n = 724) or PALO 0.5 mg (n = 725) on Day 1; following cycle 1, patients could participate in a multi-cycle extension phase. In study 2 (MEC or HEC), patients were randomized 3:1 to receive a single oral dose of NEPA on Day 1 (n = 309) or oral aprepitant (APR) 125 mg plus oral PALO 0.5 mg on Day 1, then APR 80 mg/d on days 2 and 3 of each cycle (n = 103). In both studies, all patients also received dexamethasone. Efficacy endpoints included complete response (CR; no emesis, no rescue medication) and no significant nausea. Results: In both studies, CR rates were consistently numerically higher with NEPA (Study 1 range: 77%-89%; Study 2 range: 83%-93%) than with PALO (Study 1; range: 69%-83%) or APR/PALO (Study 2; range: 78%-88%) in each cycle up to cycle 6 (Table). In both studies, rates of no significant nausea in the NEPA group were similar to or higher than in the control group. NEPA was well tolerated in both studies; treatment-related adverse events included constipation and headache. Conclusions: These studies demonstrate sustained efficacy of NEPA (administered as a single dose on Day 1) across multiple cycles of MEC or HEC for prevention of CINV in the delayed phase. Clinical trial information: 2009-016775-30; 2010-023297-39. [Table: see text]
Are patients with triple-negative breast cancer screened for <i>BRCA</i> mutations according to NCCN guidelines?
Authors: Staci Aubry, Lindsay Floch Petersen, Kelly Burgess, Ruta D. Rao, Katherine Kopkash, Andrea Madrigrano
Journal: Journal of Clinical Oncology (2015)

7 Background: Ten to 25 percent of patients diagnosed with breast cancer have triple negative breast cancer (TNBC), defined as tumors negative for estrogen, progesterone, and Her2-neu receptors. TNBC is more aggressive than receptor positive cancer. The National Comprehensive Cancer Network (NCCN) recommends BRCA genetic testing for women less than age 60 when diagnosed with TNBC. Methods: The Commission on Cancer registry tumor database was queried for TNBC from 2006 to 2013. Patient demographics were analyzed. Data regarding pathologic details and BRCA testing was collected. Analyses using the Fisher's exact test were conducted. Results: TNBC tumors were identified in the database (n = 173). Sixty-one percent (105/173) of patients were less than 60 years of age, therefore BRCA testing was indicated. Fifteen patients were BRCA positive. Eighty-three percent (87/105) of patients underwent BRCA testing. Seventeen percent (18/105) of patients did not receive BRCA testing that should have under the current guidelines. Patients that did not undergo recommended BRCA testing were more likely to be greater than or equal to 55 years of age (p = 0.002), African-American (p = 0.001), have Medicaid listed as a primary payer (p = 0.021), and have American Joint Commission on Cancer (AJCC) stage 3 disease (p = 0.014). Conclusions: Risk factors for not completing BRCA testing include older age, African-American race, Medicaid insurance status, and stage 3 disease. Health provider awareness of this opportunity for improvement is important to decrease these health disparities. [Table: see text]
Post-operative C-reactive protein concentration: A potential therapeutic target following surgery for colorectal cancer?
Authors: David G. Watt, James Hugh Park, Stephen Thomas McSorley, Paul G. Horgan, Donald C McMillan
Journal: Journal of Clinical Oncology (2016)

597 Background: Post-operative C-reactive protein concentrations (CRP) have been reported to be associated with the development of complications following surgery for colorectal cancer (CRC). The development of complications and an exaggerated post-op CRP are associated with poor long term survival. However, whether this is due to the complication or to the CRP concentration remains unclear. Therefore, the aim of the present study was to determine whether post-op CRP concentrations, independent of post-op complications, were associated with poor long term survival following surgery for CRC. Methods: Included patients were obtained from a prospectively maintained database of CRC resections from a single institution (1999-2013). The relationship between post-op CRP concentrations and overall survival (OS) was examined using Cox regression analysis. Results: 813 patients were included. The majority of patients were &gt; 65 yrs (67%), male (55%) and underwent elective surgery (90%). 257 patients (32%) suffered a complication. Median follow up was 49 months with 314 deaths. In those undergoing elective surgery, 508 patients had an uncomplicated post-op course. In these patients, post-op CRP was significantly lower, on post-op days 2, 3 and 4 (p &lt; 0.001) compared to those with complications. On univariate survival analysis, CRP concentrations on day 2 (HR 1.003, p = 0.008), 3 (HR 1.003, p = 0.024) and 4 (HR 1.003, p = 0.019) were associated with poorer overall survival. On multivariate analysis, adjusting for age, sex and TNM stage, day 2 CRP (HR 1.003, p = 0.006), age (HR 1.70, p &lt; 0.001) and TNM stage (HR 1.61, p &lt; 0.001) were independently associated with poorer survival. On multivariate analysis, adjusting for age, sex and TNM stage, day 3 CRP (HR 1.003, p = 0.030), age (HR 1.70, p &lt; 0.001) and TNM stage (HR 1.63, p &lt; 0.001) were independently associated with poorer survival. Conclusions: In patients undergoing elective surgery for CRC who have an uncomplicated post-op course, the post-op day 2 and 3 CRP concentrations were independently associated with poorer survival. Therefore, CRP could be considered a potential therapeutic target in future attempts to try and improve outcomes following surgery for CRC.
Association of lower patient ratings of physician communication with need for symptom management in lung and colorectal cancer patients.
Authors: Anne M. Walling, Nancy Lynn Keating, Katherine Leslie Kahn, Sydney Morss Dy, Jennifer Malin, Neeraj K. Arora, Jennifer W. Mack, John L Adams, Anna Liza M. Antonio, Philip Pantoja, Diana M. Tisnado
Journal: Journal of Clinical Oncology (2014)

153 Background: Symptoms are prevalent among cancer patients, but little is known about how often patients’ needs for symptom management are met or what factors are associated with unmet needs. Methods: Patients with lung and colorectal cancer from the diverse nationally-representative Cancer Care Outcomes Research and Surveillance cohort completed a survey approximately 4-6 months following diagnosis (n=5,422). We estimated the prevalence of unmet needs for symptom management during the 4 weeks prior to the survey, with unmet needs defined as patients reporting that they wanted but did not receive help for at least one symptom (pain, fatigue, depression, nausea/vomiting, cough, dyspnea, diarrhea). Using a pre-specified conceptual model, we identified patient factors associated with unmet need using multivariable logistic regression with random effects (fixed slopes model with random intercepts for each Primary Data Collection Research site). We also tested whether clinical visits before the interview were associated with unmet need. Results: Overall, 15% (791/5,422) of patients had at least one unmet need for symptom management. Adjusting for patient sociodemographic and clinical factors, African American race, being uninsured or poor, having lung cancer versus colorectal cancer, early- vs. late-stage disease, and the presence of moderate to severe symptoms were associated with greater unmet need (all p&lt;.05). Patients who rated their physicians communication score below 80 (on 1-100 scale) had adjusted rates of unmet need that were more than twice those of patients who rated their physicians with a perfect communication score (23.0% v. 10.0%, OR=3.05, p&lt;0.001). Neither visits with specialty physicians (medical oncology, radiation oncology, surgery, or primary care) nor the total number of outpatient visits in the 28 days before the interview were associated with unmet need (all p&gt;.05). Conclusions: A significant percentage of newly diagnosed lung and colorectal cancer patients report unmet needs for symptom management. Interventions to improve symptom management should consider the importance of physician communication to the experience of disease.
A phase I dose-escalation and pharmacokinetic (PK) evaluation of an oral AKT inhibitor, LY2503029 (LY).
Authors: S. A. Limentani, H. Burris, A. P. Anderson, L. H. Brail, D. Satonin, I. Gueorguieva, S. Jones, J. R. Infante, J. C. Bendell
Journal: Journal of Clinical Oncology (2011)

e13575 Background: AKT, a serine/threonine kinase, is constitutively activated in a wide variety of cancer types and activation of the PI3K/AKT pathway is frequently associated with increased neovascular formation and metastasis as well as resistance to oncolytic and hormone therapy. There has also been reported activity of PI3K pathway inhibitors in mesothelioma patients. LY2503029 (LY) is a potent, low nM inhibitor of all three isoforms with preclinical efficacy in vivo and in vitro. Methods: In this study we investigated the safety and PK of LY in patients with advanced solid tumors. A total of 14 patients were treated. Doses of LY of 10-240 mg BID have been explored in a one week on, one week off schedule. Results: The most frequently reported toxicities attributed to LY were Gr 1 nausea (64%), Gr 1-2 diarrhea (55%), Gr 1 fatigue (46%) and Gr 1-2 vomiting (46%). The maximum tolerated dose (MTD) was exceeded in the 240 mg cohort with two patients reporting Gr 3 diarrhea that was not amenable to maximal medical intervention. Thus the MTD was determined to be 160 mg BID. Pharmacokinetic analyses indicated that at steady state across the dose range, the median time to maximum concentration ranged from 0.5 to 6 hours postdose, with a terminal half-life of 2-3 hours. The exposure at 160 mg BID was significantly lower than the predicted efficacious dose, and a less than proportional increase in exposure with a doubling of dose from 80 to 160 mg BID was observed. Furthermore the human metabolite profile was also significantly different than the preclinical metabolite profile, indicating that exposure to metabolites of LY was much greater than LY parent exposure. For these reasons the study was terminated, however, patients were allowed to stay on study until progression. One patient in the 80 mg cohort with malignant pleural mesothelioma (MPM) refractory to chemotherapy has been on study for over 35 cycles (18 months), has had significant clinical improvement, and continues on therapy. Conclusions: Although this AKT inhibitor is no longer in development, a clinical signal was seen in a patient with MPM.
Randomized, multicenter, phase II trial of compound Chinese herbal extract LC09 versus placebo for external treatment of hand-foot syndrome induced by anticancer therapy.
Authors: L. Jia, Y. Lou, A. Tian, S. Zhu, X. Zhang
Journal: Journal of Clinical Oncology (2011)

9049 Background: Hand-foot syndrome (HFS) and hand-foot skin reaction (HFSR) induced by anticancer therapy can impact quality of life (QoL) and may lead to dose modification or treatment interruption, even when the therapy may prove beneficial. The trial was designed to evaluate the efficacy and safety of LC09, an external compound Chinese herbal extract, versus placebo for HFS/HFSR. Methods: Eligible patients (pts) with HFS/HFSR grade≥1 (NCI-CTCAE v3.0) after anticancer therapy. Pts were randomly assigned 2:1 to receive LC09 (Arm 1) versus placebo (Arm 2). Pts soaked their hands and feet in LC09 or placebo lotion for 20 minutes, twice daily for 7 days. NCI grade of HFS/HFSR, NRS scale of pain and DLQI (Dermatology Life Quality Index) were assessed at baseline, and at 1 week. Pts also completed a daily diary to document symptoms, side effects and medication compliance. Evaluation criteria, CR as symptoms disappear completely, PR as NCI Grade decreases more than 1 level, PD as symptoms or Grade increased, Total response rate as CR+PR. Results: 102 pts from 3 centers were enrolled. Arms were well balanced. Median age [range] was 59 [47-80], male/female was 62/40. NCI Grade was 1/2/3, 4/21/43 in Arm 1, 3/13/18 in Arm 2. Anticancer therapy included Capecitabine (48%), Sorafenib /Sunitinib (34%) and others (18%). In Arm 1/Arm 2, Total response rate was 91.2%/32.3%, CR 25.0%/2.9%, PR 66.2%/29.4%, PD 1.2%/20.6%. The mean score of QoL before and after treatment were 19.90±4.85 and 7.60±5.88 in Arm 1, 17.76±4.67 and 15.41±7.34 in Arm 2 (out of a total of 30, p<0.001). The most significant complaint was pain, the mean score were 5.98±1.87 and 1.99 ±2.05 in Arm 1, 5.15±1.59 and 4.53 ±2.71 in Arm 2 (NRS scale of 0-10, p<0.001). The average time from therapy beginning to pain relieves in Arm 1 was 2.3±1.0 days. The medication compliance was 98.7% in Arm 1,93.3% in Arm 2. No side effect such as allergy or infection related to LC09 was found. Conclusions: Compound external Chinese herbal extract LC09 can treat HFS/HFSR, which is safe and especially effective for relieving pain. Thus LC09 had trends towards a higher QoL and towards continuous beneficial anticancer therapy.