tbuckley/cabot-search huggingface dataset:
Use of germ-line polymorphisms in genes involved in the IGF pathway to predict efficacy of cetuximab independent of K-ras in mCRC patients (IMCL-0144).
Authors: T. Winder, W. Zhang, D. Yang, Y. Ning, P. O. Bohanes, S. Hu-Lieskovan, D. J. Mauro, C. Langer, E. K. Rowinsky, H. Lenz
Journal: Journal of Clinical Oncology (2010)

3562 Background: Insulin-like growth factor (IGF) signaling pathway is an important growth-regulatory pathway involved in the CRC progression. Previous studies showed that activation of the IGF1-Receptor (IGF1R) may result in resistance to anti-EGFR targeted treatment. We tested whether germ-line variations in the IGF1, and IGF1-R genes are associated with clinical outcome in mCRC patients treated with cetuximab. Methods: Tissue samples of 130 patients enrolled in a phase II clinical trial of cetuximab monotherapy were analyzed. gDNA was extracted from dissected FFPE tumor tissue and K-Ras mutation status and six potentially functional polymorphisms were analyzed using direct DNA-sequencing and PCR-RFLP. Results: In univariate and multivariate analysis five IGF pathway SNPs were significantly associated with PFS or OS (Table). Response rate was significantly increased with 50% for IGF1rs2946834 (AA) and 24% for IGF1rs6214 (CC) (univariate p=0.0025 and p=0.042, respectively) in K-Ras wild-type patients. In recursive partitioning we were able to identify subgroups of patients with PFS of 1.1 to 4.0 months (HR: 4.97–Reference) and with OS of 2.0 to 10.1 months (HR: 6.29–Reference). Conclusions: Our data suggest that IGF pathway SNPs may be potential molecular markers to predict efficacy of EGFR inhibitors. Prospective larger studies are warranted to validate our findings. N PFS OS Median, mo (95% CI) P* uni-variate P† multi-variate Median, mo (95% CI) P* uni-variate P† multi-variate IGF1rs6214 0.038 0.008 0.044 0.01 TT 16 1.1 (1.1, 1.3) 2.3 (2.0, 6.4) CC/CT 106 1.3 (1.3, 2.0) 6.5 (4.8, 8.2) IGF1rs2946834 <.0001 0.001 0.15 0.17 GG 58 1.5 (1.3, 2.6) 6.6 (3.7, 8.6) AG 45 1.2 (1.2, 1.3) 4.4 (2.7, 7.0) AA 18 2.6 (1.3, 5.4) 8.9 (4.1, 11.5) IGF1 rs7136446 0.034 0.38 0.026 0.034 CC 30 1.3 (1.2, 3.9) 6.5 (4.1, 10.5) CT 36 1.2 (1.2, 1.4) 3.4 (2.3, 6.4) TT 51 1.5 (1.3, 2.6) 7.5 (5.3, 10.7) IGF1Rrs2272037 0.79 0.66 0.039 0.28 TT 34 1.3 (1.2, 2.4) 8.7 (4.9, 14.0) CT/CC 79 1.3 (1.2, 2.3) 6.3 (3.7, 7.9) IGF1Rrs2016347 0.080 0.27 0.038 0.033 TT 46 2.3 (1.3, 3.0) 8.2 (6.3, 10.7) GT/GG 66 1.3 (1.2, 1.4) 4.2 (3.4, 7.5) * Log-rank test. † Adjusted for race, ECOG, K-Ras, Rash, EGFR +497G>A, COX-2 +8473T>C, EGF+61A>G. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Bristol-Myers Squibb, ImClone Systems, Merck Bristol-Myers Squibb, ImClone Systems Bristol-Myers Squibb
Docetaxel plus capecitabine in the treatment of previous anthracycline-treated patients with metastatic breast cancer
Authors: A. Bensalem, K. Bouzid
Journal: Journal of Clinical Oncology (2009)

e12014 Background: Anthracyclines have been considered the challenge of the treatment of metastatic breast cancer. Docetaxel has changed this belief. We conducted a study in previously anthracyclines treated metastatic breast cancer by the regimen docetaxel 75 mg/m2 Day 1 - capecitabine 2500 mg/m2 day split-up over 2 daily doses from Day 1 to Day 14; every 21 Days. Methods: Patients were eligible if they had metastatic breast cancer after an adjuvant setting by anthracyclines. All patients had measurable disease, PS ≤ 2, adequate organ function. Results: From April 2004 to June 2006, 18 patients were enrolled in the study and were evaluated for the toxicity and preliminary responses to the treatment. 100 % of patients had metastatic breast cancer. The sites of metastases were liver in 14 ( 77.7%), lung in 5 (27.7%) and bone in 9 (50%). 11 patients (61.1%) had 1 or 2 metastatic sites, 7 (38.9%) had 3 metastatic sites. All of 18 patients were assessed for toxicity. The main toxicities were as follows: neutropenia grade 3 in 3 patients (16.6 %), anemia grade 2–3 in 2 patients (11.1%), fatigue in 2 patients (11.1%), hand-foot syndrome in 7 patients (38.9%), vomiting-nausea in 4 patients (22.2%), diarrhea in 2 patients (11.1%), liver toxicity in 3 patients (16.6%). The objective response was obtained in 8 patients (44.4%) (Complete response in 3 patients (16.6%), partial response in 5 patients (27.7%). Median response duration was 9 months (range 4 - 17). 7 Patients (38.9%) had stable disease, progression was observed in 3 (16.6%) of patients. Conclusions: In this preliminary analysis, the combination of docetaxel - capecitabine in the treatment of previously anthracyclines treated metastatic breast cancer appears to be an active schedule. It is safe and active, with a manageable toxicity profile and a good clinical activity. No significant financial relationships to disclose.
Impact of Single or Associated CMV, EBV and BK Virus Reactivation Early after Allogeneic Hematopoietic Stem Cell Transplantation on Relapse Incidence
Authors: Mauricette Michallet, Mohamad Sobh, Sandrine Leroy, Fiorenza Barraco, Xavier Thomas, Sophie Ducastelle, Bruno Lina, Florence Morfin, Florence Ader, Emilie Frobert, Franck E. Nicolini, Anne-Sophie Michallet
Journal: Blood (2014)
Antitumor Activity of a <italic>Streptococcus pyogenes</italic> Preparation (OK-432). I. Sequential Effector Mechanisms Following a Single OK-432 Injection in F344 Rats Leading to the Rejection of Syngeneic MADB 106 Tumor Cells<xref ref-type="fn" rid="FN2">2</xref><xref ref-type="fn" rid="FN3">3</xref>
Authors: H Fukui, C W Reynolds
Journal: JNCI Journal of the National Cancer Institute (1987)

The effector mechanisms evoked in tumor-bearing rats following a single injection of the avirulent Su strain of type 3, group A Streptococcus pyogenes (OK-432) were sequentially examined. F344 rats challenged ip with a lethal dose of the syngeneic MADB106 mammary carcinoma could survive more than 100 days when given 50 mg OK-432/kg ip 1 day after tumor challenge. When the responsible effector mechanisms were examined in this therapeutic model, two distinct effector phases distinguished by the number of tumor cells were evident. Phase I, 1-6 days following OK-432 injection, resulted in a sharp decrease in tumor cell numbers and was related to the direct antitumor cytotoxicity of OK-432 and was coincident with an increase in the number of polymorphonuclear neutrophils. However, by day 6 a sharp increase in tumor cell numbers was again observed. Subsequently, a second phase of tumor cell destruction was observed 7-20 days following OK-432 injection and was reflected in a strong lymphocyte-mediated cytotoxicity response as well as the production of complement-dependent cytotoxic antibody against the MADB106 tumor cells. Further, the adoptive transfer of either peritoneal exudate cells or sera from the phase II animals revealed that both factors may be responsible for the antitumor activity observed in this therapeutic model. In conclusion, this study has demonstrated that the antitumor effects seen with OK-432 are due to a combination of sequential effector mechanisms leading to the eventual rejection of established tumor.
Immunity to MUC1 in pancreatic and breast cancer
Authors: B. A. Geller, A. J. Lepisto, G. M. Ahrendt, O. J. Finn, R. K. Ramanathan, A. M. Brufsky
Journal: Journal of Clinical Oncology (2007)

21166 Background: A cancer vaccine composed of MUC1 loaded DCs was effective at inducing tumor rejection in MUC1 transgenic mice. We present data from a phase IB clinical trial of the same vaccine in patients with pancreatic cancer. Preliminary analysis of this trial was reported at ASCO 2004,# 2578. Our current studies based on the results of this trial explore the importance of anti-MUC1 immunity in patients with early breast cancer, aiming to create a strong rationale for boosting these responses with vaccination in adjuvant settings. Data from both studies will be presented. Methods: The objectives of the vaccine trial were to evaluate toxicity of the vaccine, its ability to boost immunity and clinical outcome. Patients received autologous DC loaded with MUC1 100mer peptide every 3 weeks for a total of 3 doses and a booster dose 6 months later. Blood samples were obtained prior to each dose and at various times post vaccination. For the current study, 100 preoperative/pretreatment peripheral blood samples have been collected prospectively from patients with early breast cancer. Multiple immune parameters are being assessed in each group. Results: Data from extensive immune response analyses of the pancreatic cancer vaccine will be presented in detail at AACR 2007, and summarized here to provide the basis and comparison for our ongoing studies in early breast cancer. 4/12 patients in the vaccine study are alive without recurrence at three years. Even though effector and regulatory T cell responses were detected in several patients, none could be correlated with long-term survival. Several patients had anti-MUC1 antibody responses that remained stable following vaccination, which also did not correlate with survival. Ongoing studies in early breast cancer are assessing the potential differences in the quality of anti-MUC1 responses between early and late stage disease. Conclusions: In the setting of advanced disease, such as pancreatic cancer, the vaccine appears to have an effect on keeping regulatory T cells low and cellular and humoral immunity stable, without causing any significant toxicity. Ongoing studies in early breast cancer are aiming to define the immune parameters that might predict increased survival. No significant financial relationships to disclose.
Introducing HIPAA: Triple the cost and triple the time for patient recruitment to the SELECT study
Authors: N. S. Gorby, M. S. Wolf, C. L. Bennett
Journal: Journal of Clinical Oncology (2004)

6009 Background: The Health Insurance Portability and Accountability Act of 1996 (HIPAA) (45 CFR Parts 160 and 164) was enacted in April 2003 to preserve confidentiality of personally identifiable “Private Health Information” and to provide a mechanism of authorization for appropriate disclosure. Since April 2003, Institutional Review Boards have assumed the task of interpreting various legislative elements of HIPAA and making recommendations on research protocols. We evaluated the economic impact of HIPAA regulations on the Selenium and Vitamin E Trial, an NCI sponsored chemoprevention trial. Methods: A formative evaluation was conducted of the recruitment process at baseline for a companion study evaluating the effectiveness of a minority recruitment strategy for SELECT. Study accrual data was analyzed in weekly increments beginning January 2003 to December 2003. Patients who consented to the study prior to April 2003 were considered “pre-HIPAA”, while patients recruited on or after June 2003 were considered “post-HIPAA”; accounting for a 6 week delay incurred by the IRB review of the revised protocol. Results: A 70.1% decrease in patient accrual (6.7 pts/week vs. 1.9 pts/week, p<.001) occurred following HIPAA enactment. Taking into account a research assistant's salary and time, pre-HIPAA compliance, an accrued patient required 4.1 hours of RA time (personnel cost of $57), while post-HIPAA accrual required 14.1 hours of RA time (personnel cost of $197). Recruitment pre-HIPAA was on target to complete accrual in 60 weeks time (N=400), compared to post-HIPAA accrual, which would require 171 weeks to recruit the remaining 333 patients to the study at the current rate. Conclusions: Although privacy is of the utmost importance in a world of electronic patient information, HIPAA places a considerable burden on research, which questions the ability to conduct cancer studies in a timely and cost-effective manner. No significant financial relationships to disclose.
Suicidal behavior of children: a review with implications for research and practice
Authors: C R Pfeffer
Journal: American Journal of Psychiatry (1981)

The author reviews the environmental and psychological factors associated with suicidal behavior of children aged 6-12 years; the incidence of such behavior seems to be increasing. Assessment of a child's suicide potential should focus on such issues as depression, family communication patterns, the child's concepts about death, and the state of ego functioning. The author emphasizes the need for more systematic investigations of suicidal behavior among children, more precise methods of interviewing and recognizing potentially suicidal children, and widespread education of the public about this life threatening
Postmastectomy radiotherapy: more than locoregional control.
Authors: L J Pierce, A S Lichter
Journal: Journal of Clinical Oncology (1994)

Article Tools Article Tools OPTIONS & TOOLS Export Citation Track Citation Add To Favorites Rights & Permissions COMPANION ARTICLES No companion articles ARTICLE CITATION DOI: 10.1200/JCO.1994.12.3.444 Journal of Clinical Oncology - published online before print September 21, 2016 PMID: 8120543 Postmastectomy radiotherapy: more than locoregional control. L J PiercexL J PierceSearch for articles by this author , A S LichterxA S LichterSearch for articles by this author https://doi.org/10.1200/JCO.1994.12.3.444 First Page PDF © 1994 by American Society of Clinical Oncology
Pathologic Effects in Rats Surviving Prenatal and Neonatal Administration of 1,3-bis(2-Chloroethyl)-1-Nitrosourea2
Authors: Elvira deC. Weiss, Humberto Cravioto, Joseph F. Weiss, Joseph Ransohoff
Journal: JNCI Journal of the National Cancer Institute (1973)

Long-term pathologic effects were studied in rats exposed transplacentallyto 1,3bis(2-chloroethyl)-1-nitrosourea (BCNU) or treated orally with BCNU at 10 days of age. Dental anomalies (macrodontia and underdevelopment or absence of incisors)were observed in 14 of 31 rats of the CFE and Long-Evans strains that received 5–10 mg/kg BCNU orally and survived longer than 60 days. Hepatotoxicity, including proliferation of bile canaliculi, Cirrhosis, and granulomas, was a delayed toxic effect seen in rats treated during development with BCNU. A malignant neurinoma of the trigeminal nerve, which may have been chemically induced, was noted in a group of 30 rats that survived transplacental administration of BCNU. Three other tumors were found in this group, but they did not differ significantly in number and type from tumors in old untreated rats. The toxic effects and the “teratogenic” effect observed,taken together, suggest that BCNU is probably carcinogenic in the rat. However, quantitative aspects of oncogenic activity may be difficult to determine, since only low doses permit long-term survival, and induced tumors must be distinguished from those occurring spontaneously in old animals.
BIBW 2992 versus cetuximab in patients with metastatic or recurrent head and neck cancer (SCCHN) after failure of platinum-containing therapy with a cross-over period for progressing patients: Preliminary results of a randomized, open-label phase II study.
Authors: T. Y. Seiwert, P. M. Clement, D. Cupissol, J. Del Campo, H. de Mont-Serrat, H. C. Thurm, A. S. Blackman, E. E. Cohen
Journal: Journal of Clinical Oncology (2010)

5501 Background: BIBW 2992 is a novel, potent, orally bioavailable irreversible inhibitor of EGFR/HER1 and HER2 receptor tyrosine kinases. Preclinically, BIBW 2992 also displays potent activity against multiple EGFR mutations, including the EGFRvIII mutation. Methods: Patients with metastatic or recurrent SCCHN after failure of platinum-containing therapy were randomized to receive 50 mg of BIBW 2992 daily or weekly cetuximab 400 mg/m2 (loading) and 250 mg/m2 thereafter until disease progression or undue side effects (stage 1). Cross-over to the opposite treatment was allowed upon progression (stage 2). Response was assessed according to RECIST every 8 weeks. Correlative studies including markers of EGFR signalling and presence of EGFRvIII are pending. Results: 124 patients were randomized; 15/124 patients were not evaluable for tumor response evaluation. Of the 109 patients evaluable, 35 have not yet undergone postrandomization tumor imaging. Preliminary best response analysis for 74/109 patients in stage 1 is reported here. Among 34/74 patients randomized to BIBW 2992, 6/34 (18%) patients showed a partial response (PR), 18/34 (53%) patients revealed stable disease (SD) and 10/34 (30%) patients showed progressive disease (PD). Among the 40/74 patients randomly assigned to cetuximab, there were 3/40 (8%) patients with PR as best response. 20/40 (50%) patients with SD and 17/40 (43%) patients with PD. Preliminary safety analyses revealed side-effect profiles typical for EGFR inhibitors, with diarrhea and skin-related AEs as the primary BIBW 2992-related AEs. Conclusions: Preliminary efficacy analysis based upon response rate suggests that BIBW 2992 is active in patients with metastatic or recurrent SCCHN after failure of platinum-containing therapy and compares favorably to patients receiving cetuximab. Both drugs showed a comparable safety profile. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Boehringer Ingelheim Boehringer Ingelheim
Vinflunine (VFL) in combination with gemcitabine (GEM) for treatment of advanced non-small cell lung cancer (NSCLC) in chemonaive patients (pts): Preliminary results of the phase I and pharmacokinetic study
Authors: E. Lemarie, J. Bennouna, F. Grossi, M.-C. Pinel, H. Sennellart, B. Longerey, J.-Y. Douillard
Journal: Journal of Clinical Oncology (2005)

7266 Background: VFL (Javlor) is a novel semi-synthetic vinca-alkaloid that has shown higher in vivo antitumour activity than vinorelbine in several human tumour models. In NSCLC, non-platinum doublets are of major interest. Methods: This trial was designed to determine the recommended dose (RD) of the combination in pts with advanced NSCLC. Were defined as dose limiting toxicity (DLT) any of the following adverse event occurring during the cycle 1: neutrophils < 0,5 x 109/L for ≥ 7 days or < 0,1 x 109/L for ≥ 3 days; platelets < 25 x 109/L or thrombocytopenia with bleeding or requiring platelet transfusion; febrile neutropenia or any grade (G) 3 or 4 major organ toxicity according to the NCI-CTC scale; withdrawal of any patient after the 1st cycle due to delayed recovery from toxicity. Pharmacokinetic blood sampling was performed to investigate potential interaction VFL-GEM. Results: Three dose-levels of the combination were investigated in 12 pts (9 males, 3 females); WHO performance status 0: 7 pts; 1: 5 pts; median age: 57.7 years (44.5–76.2) all evaluable for RD determination. All pts were chemonaive and presenting with stage IB: 1 pt, IIA: 1 pt and IV: 10 pts. No DLT was observed in the first dose level explored, VFL 280 mg/m2 on day (D) 1 and GEM 1000 mg/m2 on D1–8. The maximum tolerated dose was established at the dose level VFL 320 mg/m2 D1 and GEM 1250 mg/m2 D1–8 in which 3 pts experienced DLT: 1 pt had febrile neutropenia and G3 constipation, 1 pt G3 constipation and 1 pt experienced a brief episode of G4 hypertension after GEM dosing on day 8. The dose level 2, vinflunine 320 mg/m2 D1/GEM 1000 mg/m2 D1–8, was established in 6 pts as the recommended dose (RD). To date, a total of 8 pts have been treated at this RD and 6 achieved partial response according to RECIST. Preliminary pharmacokinetic analysis did not detect any drug-drug interaction of VFL and GEM when combined. Conclusions: The RD of the combination is established at VFL 320 mg/m2 given on day 1 combined with GEM 1000 mg/m2 given on days 1 and 8 every 3 weeks. Final results of this study grouping safety and the antitumour activity will be presented at the meeting. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Pierre Fabre
Renal insufficiency in cancer patients: Prevalence and implications on anticancer drugs management. Results of the IRMA study
Authors: V. Launay-Vacher, S. Oudard, N. Janus, C. Le Tourneau, O. Rixe, X. Pourrat, J. Gligorov, P. Beuzeboc, G. Deray, J. Morere
Journal: Journal of Clinical Oncology (2006)

8603 Background: Patients with abnormal renal function are at high-risk for drug-induced nephrotoxicity. Furthermore, near half anticancer drugs are predominantly excreted in urine and dosage adjustment in RI is therefore a crucial issue. In 2005, the IRMA study (Insuffisance Rénale et Médicaments Anticancéreux) thus investigated the prevalence of RI in cancer patients and the profile of anticancer drugs prescribed. Methods: Data were collected for cancer patients presenting at one of the 14 IRMA centers in February 1st-15th or October 1st-15th, 2004: type of tumour, sex, age, weight, serum creatinine (SCR), haemoglobinemia, anticancer drugs. Dialysis and myeloma patients were not included. The prevalence of SCR&gt;110 μmol/L was assessed. GFR was estimated with the Cockcroft-Gault (CG) and the abbreviated MDRD (aMDRD) formulae and patients were classified according to their K/DOQI stage of RI (Table). Anticancer drugs necessitating dosage adjustment and those potentially nephrotoxic were identified. Results: 4,684 patients (Breast, 1,898; Colorectal, 573; Lung, 445; Ovarian, 270; Prostate, 222) were included: mean age 58.1 years, weight 65.8 kg, sex-ratio 0.55. The prevalence of elevated SCR was 7.2% and those of GFR &lt;90 ml/min was 57.4% with CG and 52.9% with aMDRD. 53.4% of the 7181 prescriptions needed dosage adjustment and 79.9% of treated patients (n=3823) were receiving at least one drug needing dosage adjustment. 53.3% of prescriptions were potentially nephrotoxic and 80.1% of treated patients received at least one nephrotoxic drug. 46.8% had a serum haemoglobin lower than 12 g/dL and still 25.9% were lower than 11 g/dL. Conclusions: The results of the IRMA study showed that RI is highly frequent in cancer patients and that 80% of the patients receive potentially nephrotoxic drugs and/or for which dosage must be adjusted in RI. Furthermore in IRMA patients, anemia was still highly frequent. [Table: see text] No significant financial relationships to disclose.