tbuckley/cabot-search huggingface dataset:
The role of contrast-enhanced ultrasound in detection of liver metastases from colorectal cancer: A prospective monocentric study
Authors: C. Mucciarini, S. Bellentani, G. Razzini, I. Bernardini, F. Artioli, A. Iop, S. Blanzieri
Journal: Journal of Clinical Oncology (2009)

e15105 Background: Up to 15–25% of patients with colorectal cancer (CRC) will develop metacronous liver metastases during the follow up. The management and prognosis of these patients depend heavily on the early detection of metastases. The most effective surveillance strategy has not yet being extablished. The introduction of second generation ultrasound contrast agents have improved the ability of contrast-enhanced ultrasound (CEUS) in detecting and characterizing liver lesions, showing that its accuracy is comparable to that of spiral CT and MRI with a liver contrast agent, with a cost and a time saving. We tested the sensitivity and specificity of CEUS in detecting liver metastases compared with the standard imaging modalities used in the follow up of CRC. Methods: We conducted a prospective study considering all patients with a diagnosis of CRC in high risk stage II, stage III or with a previous metastasectomy of the liver. In order to detect possible metastases, the patients were followed with a follow-up schedule including a six-monthly ultrasonography alternated to an annual CT, and a six-monthly CEUS with SonoVue contrast agent for the first 3 years. Results: From January 1 st to December 2008 we executed 60 CEUS, identifying thirteen suspected liver lesions. 10/13 were confirmed metastases by CT, MRI or TC/PET. 2/13 resulted benign lesions. 1/13 resulted negative at the CT but positive with a MRI. Another additional case was missed by CEUS but detected by CT. CEUS improve specificity and sensitivity compared with baseline ultrasonography. We had an histological confirmation in all cases except one. The study is still recruiting patients. Conclusions: The clinical value of CEUS as a reliable alternative to CT or MRI in characterizing focal liver lesions has been expressed in various documents and guidelines. Our preliminary results confirm the similar diagnostic performance and confidence of CEUS compared to these imaging modalities in the follow up of CRC. Further clinical studies are still needed to strenghten the existing data. No significant financial relationships to disclose.
A phase III trial comparing adjuvant treatment with leuprorelin acetate 3M-Depot for 24 months with CMF chemotherapy in ER/PR + node + pre-perimenopausal breast cancer patients
Authors: D. Wallwiener, K. Possinger, P. Schmid, V. Tarutinov, L. Suchina, H. Hillger, E. Kienle, L. Maubach, S. Kahlert, M. Untch
Journal: Journal of Clinical Oncology (2004)

533 Background: Recent studies proved that ovarian ablation with LHRH-analogues is not inferior to CMF-chemotherapy in pre-perimenopausal ER/PR+ breast cancer patients (bc pts). Methods: A randomized phase III trial in pre-perimenopausal bc pts (pT1–3, N+, M0, ER+ and/or PR+) tested the H0 hypothesis that a 2 y treatment with 8 injections of leuprorelin acetate 3M-depot (LAD 3M) was not inferior (> 10 % below CMF) to 6 double cycles of CMF (C 500-, M 40-, F 600 mg/sqm/d 1 and 8 q4w). Primary endpoint was 2y- progression free survival (PFS), secondary were 5y- PFS, overall survival (OS), state of health and safety. Other parameters were E2 serum levels and menstrual status. This was a planned 2 y final (589/599 pts) and 5 y interim analysis (359/599 pts). Results: Of 599 pts randomized 526 were eligible for per protocol analysis. 2y- PFS was 80.9 % (207/256, CMF) and 83.0 % (224/270, LAD 3M). The H0 hypothesis was rejected (p = 0.0002). In CMF 51 pts (49 ongoing /145) and in LAD 3M 58 pts (46 ongoing /154) showed 5y- PFS. Mean time to progression was 48.1 ± 1.1 (LAD 3M) vs. 47.3± 1.1 mths (CMF) (Kaplan-Meier, p = 0.866). OS was 98.7 % (152/154, LAD 3M) vs. 97.2 % (141/145, CMF, n.s.). SAEs were reported in 14/294 pts (4.8%, LAD 3M) vs. 27/295 pts (9.2%, CMF). CMF was more often associated with chemotherapy side effects like vomiting, weakness, alopecia compared to LAD 3M which was associated with typical menopausal symptoms like hot flushes, sweating. CMF led to a longer time off work compared to LAD 3M (155±135d vs. 98±120d, p<0.001). LAD 3M led to a more rapid and persistent E2- and menstrual suppression. After 3 years cessation of menstruation was present in 43.7% and 44.9% in the LAD 3M and CMF group respectively. Conclusions: In HR+, N+, pre-perimenopausal bc pts 8 injections of LAD 3M were not inferior to six double cycles of CMF (d 1and 8) with regard to PFS and OS. Side effects had a different profile with typical cytostatic associated adverse events and longer time off work in the CMF group. This study was sponsored by Takeda-Pharma, Germany. Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Takeda Pharma, Germany Takeda Pharma, Germany Takeda Pharma, Germany Takeda Pharma, Germany
Sequential combination of paclitaxel-carboplatin and paclitaxel-liposomal doxorubicin as 1<sup>st</sup> line treatment in patients with ovarian cancer: A multicenter phase II clinical trial
Authors: A. Potamianou, A. Polyzos, J. Boukovinas, C. Latoufis, N. Andoulakis, S. Agelidou, A. Kotsakis, S. Giassas, J. Varthalitis, L. Vamvakas
Journal: Journal of Clinical Oncology (2004)

5108 Background: To evaluate the efficacy and toxicity of the sequential administration of paclitaxel-carboplatin (T/C) and paclitaxel-liposomal doxorubicin (T/D) as 1st line treatment in pts with ovarian cancer. Methods: From 2/2001 to 6/2002, 52 pts with histologically proven, FIGO stage III/IV ovarian cancer were enrolled. No prior chemotherapy, radiotherapy or endocrine therapy was allowed. Other eligibility criteria included age<75 years, PS 0–2, life expectance > 6 months, adequate hepatic, renal, cardiac and bone marrow function. Median age was 60 years (range 40 to 74). In 36 pts cytoreductive surgery was performed. Patients received 4 cy of Paclitaxel 175mg/m2, 3-h infusion and Carboplatin 6 AUC both on day 1 every 3 weeks, followed by 4 additional cy of liposomal doxorubicin 40mg/m2 and Carboplatin 6 AUC both on day 1 every 3 weeks. Results: At the time of the present analysis, 41 patients were evaluable for toxicity and 39 for response. A total of 284 cy were delivered (median cy: 8/pt). Grade 3–4 neutropenia occurred in 24.7% of cy, thrombocytopenia in 6.4%. There were no episodes of febrile neutropenia. G-CSF was required in 49.6% of the cy and non-hematological toxicity was mild except alopecia. Chemotherapy was delayed in 20.4% of the cycles (median delay: 7 days, range 4–44) but due to hematological toxicity in only 9.1% of the cy. The median follow-up was 11.5 months (range 1–29 mo). 20 (51.2%) and 12 (30.8%) pts achieved CR and PR with the T/C regimen, respectively and 7 (18%) had SD. The administration of T/D regimen resulted in 3 (15.8%) additional CRs. The overall response rate was 66% (CR 44%, PR 22%), with a median duration of response of 10.2 months (range 1–25.8 mo); the time to progression was 12.1 months (range 1–28.9 mo) and the median survival has not yet been reached. Conclusions: The results of the analysis indicate that the sequential administration of paclitaxel-carboplatin followed by paclitaxel-liposomal doxorubicin is an active regimen with acceptable toxicity as a 1st line treatment in patients with ovarian cancer. No significant financial relationships to disclose.
Accelerated hyperfractionated chemoradiation (C-HART) plus 5-FU/MMC is superior to HART for inoperable locally advanced head and neck cancer. Final results of the German ARO 95–06 Multicentre Trial
Authors: V. G. Budach, M. Stuschke, W. Budach, M. Baumann, D. Geismar, G. Grabenbauer, I. Lammert, K. Jahnke, P. Wust, K.-D. Wernecke
Journal: Journal of Clinical Oncology (2004)

5503 Purpose: Is accelerated hyperfractionated radiation therapy with 70.6 Gy plus concurrent 5-FU/MMC (C-HART) more effective than a dose escalated HART scheme with 77.6 Gy alone? Material/Methods: The treatment consisted of 70.6 Gy plus 5-FU/MMC (C-HART) versus a 10% dose escalated HART of 77.6 Gy alone. Concurrently with C-HART MMC at a dosage of 10mg/m2 on days 5 and 35 and 5-FU at a dosage of 600mg/m2 as 120 hrs. c.i. during days 1–5 were delivered. Macroscopic tumor manifestations received 70.6 Gy (C-HART) or 77.6 Gy (HART), lymphatic drainage with high or low risk of metastatic spread, 60 Gy and 50 Gy, respectively. Results: The median follow-up period was 60 months for 384 patients, which were all analyzed according to the intent to treat principle. 84% of all patients were males, 16% females. 59.5% of all patients suffered from oropharyngeal, 32.4% from hypopharyngeal and 8.3% from oral cavity tumors. 93.8% of all patients (n=350) were diagnosed with stage IV and only 6.2% (n=23) with stage III. Patients were stratified according to tumor site, N-stage and participating centre. The actuarial locoregional control, overall and progressionfree survival rates at 5 years for C-HART versus HART, respectively, were 49.9% (95% CI: 42.3–58.7%) vs. 37.4% (95% CI: 30.4–46.0%, p=0.0009), 28.6% (95% CI:22.5–36.3%) vs. 23.7% (95% CI: 18.2–30.9%, p=0.02) and 29.3% (95% CI: 23.0–37.3%) vs. 26.6% (95% CI: 20.7–34.3%, p=0.009). The median LRC-period was 48 months vs. 15 mos., the OS-period 23 mos. vs. 16 mos.and the PFS-period 16 vs. 11 mos. for C-HART vs. HART, respectively. The actuarial freedon from metastases rates (C-HART vs. HART), were 51.9% (95% CI: 43.5–61.9%) vs. 54.7% (95% CI: 46.1–64.9%, p=0.58). Five and eight items, which were documented for acute and late normal tissue reactions, respectively, showed no significant difference between both treatment arms indicating equitoxicity and late morbidity. Conclusions: At equitoxic levels of acute and late normal tissue reactions for both treatment arms, C-HART is more effective than HART in all endpoints with the exception of the MFS-rates indicating an improvement of the therapeutic ratio. No significant financial relationships to disclose.
Integration of clinico-pathologic variables, mRNA, and microRNA profiles represents an optimal strategy to predict sensitivity to chemotherapeutic agents in breast cancer
Authors: K. H. Salter, B. A. Perez, C. R. Acharya, K. S. Walters, A. Anguiano, C. K. Anders, H. K. Dressman, P. K. Marcom, J. R. Nevins, A. Potti
Journal: Journal of Clinical Oncology (2008)

14567 A major challenge in oncology is the selection of the most effective chemotherapy agents for individual patients. This emphasizes the need to evaluate individual patients’ probability of responding to each chemotherapeutic agent and thus limit the agents used to those most likely to be effective. Using gene expression data and corresponding drug sensitivity on the NCI-60 cell line panel, mRNA and miRNA profiles were developed representing sensitivity to individual chemotherapeutic agents. The mRNA signatures were first tested in an independent cohort of 133 breast cancer patients treated with the TFAC (paclitaxel (T), fluorouracil (F), adriamycin (A), and cyclophosphamide (C)) chemotherapy regimen. To further dissect the biology of chemotherapeutic resistance, we applied signatures of oncogenic pathway activation (Ras, Myc, E2F, beta-catenin, Src and PI3kinase). In our study, mRNA and miRNA profiles seem to represent critical mechanisms of resistance to cytotoxic agents. Specifically, we identified that certain miRNAs have unique biologic relevance, e.g. miR17, which with Myc promotes aggressive tumor growth, is associated with anthracycline resistance. The mRNA signatures for TFAC were validated in the dataset of 133 breast tumors (P=0.002, NPV=82%). When the accuracy of the signatures was analyzed based on molecular variables, the predictive ability was independent of HER2 status but found to be greater in ER negative tumors (P=0.01), and triple negative ‘basal’ (P=0.03) tumors. Furthermore, we also show that the interplay between Myc and Rb/E2F pathways is critical to TFAC resistance. Finally, using mRNA signatures of sensitivity to other cytotoxic agents, we predict that TFAC non-responders are more likely to be sensitive to docetaxel (P = 0.04), a viable alternative therapy. Our results suggest that the optimal strategy for chemotherapy sensitivity prediction integrates molecular variables such as ER and HER2 status with corresponding miRNA and mRNA expression profiles. We also present evidence to further support the concept that analysis of molecular variables presents a rational strategy to dissecting tumor biology and identifying alternative therapeutic opportunities. No significant financial relationships to disclose.
Two phase III clinical studies of cevimeline for post-radiation xerostomia in patients with head and neck cancer
Authors: M. S. Chambers, M. R. Posner, C. U. Jones, R. S. Weber, R. Vitti
Journal: Journal of Clinical Oncology (2005)

5503 Background: Xerostomia is a frequent debilitating complication of head and neck cancer radiotherapy. Morbidities include dental caries, oral infections, and impaired quality of life. Methods: Two multicenter double-blind trials were conducted to assess the efficacy and safety of cevimeline in the treatment of radiation-induced xerostomia. Each trial enrolled subjects ≥18 years of age with head and neck cancer who had received >4000 cGy of radiation ≥4 months before entry and had clinically significant salivary gland dysfunction. Subjects were randomized to cevimeline 30 mg TID or placebo for 12 weeks, with escalation to 45 mg TID or placebo equivalent at 6 weeks if no improvement was reported. Subjects experiencing side effects after dose escalation could de-escalate to 30 mg TID. The primary efficacy endpoint was global evaluation of oral dryness, with a secondary endpoint being change in unstimulated salivary flow. Results: A total of 570 subjects (284 in the 003 and 286 in the 004 study) were randomized. In the final (visit 5) global evaluation of dry mouth in the intention-to-treat (ITT) analysis, improvement was reported by a greater percentage of subjects treated with cevimeline compared with placebo recipients (47.4% vs 33.3%, P=0.0162) in the 003 study; differences between groups were significant at visits 3 through 5 (P≤0.0162). Differences of global evaluation of oral dryness between the treatment and placebo groups were not statistically significant in the 004 study, although a high placebo response rate was observed (48.9% vs 47.6%, P=0.9565). In both studies, cevimeline-treated patients had significantly greater mean increases in unstimulated salivary flow than placebo treated patients at the final visit (ITT, P=0.0093 [003] and P=0.0215 [004]). Cevimeline was well tolerated in both studies. Adverse event frequency was comparable in the placebo and cevimeline groups, with the exception of increased sweating in the cevimeline group. Conclusions: Cevimeline 30 to 45 mg TID increased mean unstimulated salivary flow in both studies and in one study improved subjective dry mouth sensation in subjects with xerostomia following radiation therapy for head and neck cancer. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Daiichi
Post-hoc analyses of overall survival (OS) and progression-free survival (PFS) in the TRIO-013/LOGiC trial of lapatinib (L) in combination with capecitabine plus oxaliplatin (CapeOx).
Authors: Yung-Jue Bang, Shukui Qin, Hyun-Choel Chung, Jian-Ming Xu, Joon Oh Park, Krzysztof Jeziorski, Yaroslav Shparyk, Paulo M. Hoff, Alberto F. Sobrero, Pamela Salman, Jin Li, Svetlana Protsenko, Marc E. Buyse, Karen Afenjar, Vincent Houe, Agathe Garcia, Yingjie Huang, Alison Armour, Dennis J. Slamon, J. Randolph Hecht
Journal: Journal of Clinical Oncology (2015)

133 Background: Results of the primary and secondary endpoints (OS and PFS, respectively) in the primary efficacy population for the randomized, phase III trial (TRIO-013/LOGiC; NCT00680901), conducted in patients with advanced, HER2-positive upper gastrointestinal adenocarcinoma were previously presented (Hecht JR et al, ASCO 2013). Differences in OS were non-significant between the lapatinib (CapeOx + L) and placebo (CapeOx + P) arms. In prespecified analyses, a treatment effect of L was observed in Asian (majority Chinese or South Korean) patients and patients &lt;60 years (y) when comparing OS in the two arms. Methods: Here, we present the results of post-hoc analyses in TRiO-013/LOGiC which assessed OS, PFS and safety by age and by region. Results: In the Asian subgroups, median OS was longer with L compared with P (see Table). In the rest of the world (ROW) subgroups, median OS was longer in patients &lt;60 y but shorter in patients ≥60 y with L compared with P (see Table). Similar findings were observed for PFS in the 4 subgroups (see Table).More adverse events (AEs) were observed in the Asian subgroups; overall, the incidence of AEs (by region) was similar between age subgroups. Conclusions: OS and PFS were improved in Asian patients (both age subgroups) and younger patients in ROW given CapeOx + L, compared with CapeOx + P. The lower OS and PFS observed in older patients in the ROW subgroups may have affected the overall data. Further trials with CapeOx + L in Asian populations are being considered. Clinical trial information: NCT00680901. [Table: see text]
Dendritic Cells Derived In Vitro From Acute Myelogenous Leukemia Cells Stimulate Autologous, Antileukemic T-Cell Responses
Authors: A. Choudhury, J.C. Liang, E.K. Thomas, L. Flores-Romo, Q.S. Xie, K. Agusala, S. Sutaria, I. Sinha, R.E. Champlin, D.F. Claxton
Journal: Blood (1999)
A randomized double-blind placebo-controlled study of oral coenzyme Q10 to relieve self-reported cancer-treatment-related fatigue in newly diagnosed breast cancer patients.
Authors: G. J. Lesser, L. D. Case, N. Stark, S. K. Williford, J. K. Giguere, A. Garino, M. J. Naughton, M. Vitolins, M. Lively, E. G. Shaw
Journal: Journal of Clinical Oncology (2010)

9006 Background: Coenzyme Q10 (CoQ) is an antioxidant supplement with known cardioprotective effects and potential anticancer benefits. We performed a randomized, double-blind, placebo-controlled study of oral CoQ in female breast cancer patients to determine CoQ's effects on self-reported fatigue, depression and quality of life (QOL). Methods: Eligible women with newly diagnosed breast cancer and planned adjuvant chemotherapy were randomized to oral supplements of 300 mg CoQ or placebo, each combined with 300 IU Vitamin E, divided into three daily doses. Treatment was continued for 24 weeks. Participants were stratified by anthracycline (yes/no) and radiation therapy (yes/no). Blood tests, QOL measures, and serum CoQ and Vitamin E levels were obtained at baseline, 8, 16 and 24 weeks. Mixed effects models were used to assess treatment differences in outcomes over time. Results: Between 8/2004 and 3/2009, 236 women were enrolled. Treatment arms were well balanced with respect to age (range 28-85), PS (0, 1, 2) (91%, 8%, 4%), ethnicity (87% White/11%Black/2%Hispanic) and planned therapy (84% anthracycline; 61% RT). No serious adverse events were noted. At 24 weeks, there were no significant differences between the CoQ and placebo arms on the POMS-Fatigue (LS means 5.88 vs. 7.24, p = .27); FACIT-Fatigue (40.2 vs. 39.7, p = .77); FACT-B subscale (25.6 vs. 25.7, p = 0.92); or CES-D (10.1 vs. 10.5, p = 0.82). In the 86 pts with complete CoQ serum samples, baseline and 24 week CoQ levels in the CoQ and placebo arms were 0.72/1.98 and 0.77/0.82 μ g/mL, respectively. In this subset, higher CoQ levels were modestly associated with less fatigue. Conclusions: Supplementation with conventional doses of CoQ led to sustained increases in serum CoQ levels, but did not result in improved self-reported fatigue or QOL after 24 weeks of treatment in women with breast cancer receiving adjuvant therapy. The modest association between higher CoQ levels and less fatigue in patients with complete assays suggests that further exploration of the relationship between CoQ dose and self-reported fatigue may be warranted. Supported by NIH/NCI/DCP grant 3 U10 CA081851. No significant financial relationships to disclose.
Court rules that FDA cannot restrict off-label marketing
Authors: Bob Roehr
Journal: BMJ (2015)

A federal judge in New York has ruled that the Food and Drug Administration cannot restrict off-label marketing information for an approved drug so long as the information is truthful and not misleading. The judgment was based on the First Amendment—the right to free speech.

The judge, Paul A Engelmayer, issued an injunction prohibiting the FDA from bringing threatened action against Amarin Corporation for their marketing of Vascepa, a drug consisting of purified omega 3 fatty acid derived from fish oil.1

The FDA approved Vascepa for treating blood triglyceride concentrations above 500 mg/dL in 2011. But it objected to Amarin marketing the drug for treating patients with lower concentrations of triglycerides, despite evidence showing effectiveness from a study approved by the agency. The reason was a growing question as to whether …
Anti-cancer activity of NVP-TAE226, a potent dual FAK/IGF-IR kinase inhibitor, against pancreatic carcinoma
Authors: S. Hatakeyama, D. Tomioka, E. Kawahara, N. Matsuura, K. Masuya, T. Miyake, I. Umemura, T. Kanazawa, T. Honda, O. Ohmori
Journal: Journal of Clinical Oncology (2006)

13162 Background: Focal adhesion kinase (FAK) is a non-receptor cytoplasmic tyrosine kinase that regulates multiple cell functions. Elevated expression levels of FAK have been detected in various tumor samples and are closely correlated with invasive potential. Activation of integrins and the growth factor receptors result in FAK autophosphorylation at Y397 and the presentation of suitable binding sites for proteins containing either SH2 or phosphotyrosine binding domains. Recent evidences suggest that FAK plays important roles in cancer cell proliferation and survival. IGF-IR function is required for tumor cell survival, but dispensable for survival of normal cells. Therefore, a dual inhibitor of both kinases may selectively block the growth, migration, and survival of FAK- and IGF-IR- expressing tumor cells compared to proliferating and migrating normal cells. Methods: In this study, anti-cancer activity of NVP-TAE226 that is identified as a potent and selective FAK inhibitor was evaluated in cancer cell lines panel and MIA PaCa-2 pancreatic carcinoma in vivo model. Results: Mean GI 50 value of NVP-TAE226 against 37 cancer cell lines was 0.76 μmole/L. Inhibition of cancer cell proliferation was not affected by expression of P-glycoprotein, suggesting that NVP-TAE226 is not served as a substrate of P-glycoprotein. Oral administration of NVP-TAE226 efficiently inhibited MIA PaCa-2 human pancreatic tumor growth at all doses tested. Tumor stasis was observed at a dose of 30 mg/kg, qd for 7×/week and tumor regression was observed at a dose of 100 mg/kg, qd for 5×/week. All animals tolerated NVP-TAE226 treatment up to 100 mg/kg, 5×/wk, qd, po for 2 weeks with no body weight loss. Inhibition of downstream signaling such as phosphorylation of Akt at Serine473 was accompanied by inhibition of FAK phosphorylation in human pancreatic carcinoma cell lines. Conclusions: NVP-TAE226 is a novel class of selective and small molecule kinase inhibitors with a potent in vivo activity and potential therapeutic application. No significant financial relationships to disclose.