tbuckley/cabot-search huggingface dataset:
Imatinib mesylate in 18 advanced chordoma patients
Authors: P. G. Casali, S. Stacchiotti, A. Messina, E. Tamborini, C. Martini, C. Ripamonti, F. Crippa, C. Spreafico, M. Colecchia, S. Pilotti
Journal: Journal of Clinical Oncology (2005)

9012 Background: We reported (Cancer 2004;101:2086) the antitumor activity of Imatinib mesylate in 6 patients with advanced chordoma treated on an individual basis at the Istituto Nazionale Tumori, Milan, Italy, on biomolecular evidence of potential sensitivity to this agent. Other 12 patients were put on treatment thereafter, up to July 2004, before a currently ongoing Phase II study could be opened. We update/report herein efficacy data on the whole series of these 18 patients. Methods: Eighteen patients with a histological diagnosis of chordoma (originating from sacrum in 13, skull base in 3, and vertebrae in 2) started Imatinib mesylate from August 2002 to July 2004, at the daily dose of 800 mg in 14, and 400 mg in 4. M:F ratio was 9:9. Age was 14–77 (median: 56). Extent of disease was locally advanced in 12, local and metastatic in 6. Median interval from diagnosis was 5 yrs (range: 0–12). KPS was = 0–2 in 9, and = 3 in the remaining patients. Results: Two patients (11%) had a “dimensional response”, with a <50% tumor regression in bidimensional size, while other 11 patients (61%) had radiological signs of “tissue response”, with decreased contrast uptake/enhancement and/or decreased tumor density at CT/MRI, following patterns which in GIST are usually indicative of a tumor response. One patient had only a “functional response”, i.e. a decreased glucose uptake at PET scan against an unchanged radiological aspect. Some degree of subjective improvement was reported in 10 out of 14 symptomatic patients. The actuarial progression-free interval at 1 year was 88%, but 2 patients died with no evidence of tumor progression at 41 and 68 weeks, due to complications of a mostly liquefied, enormous tumor mass. Other two patients died and one stopped therapy early, in the absence of tumor progression. Thus, 11 patients are currently on therapy, after 14–70 weeks from treatment start. Conclusions: On a larger number of patients, we confirm that Imatinib mesylate has antitumor “activity” in chordoma. The potential of major clinical “efficacy” is suggested by the progression-free interval (up to 70+ weeks) seen in surviving patients with a long follow-up. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Novartis Novartis
A phase II study of neoadjuvant bevacizumab and radiation therapy for resectable soft tissue sarcomas.
Authors: S. S. Yoon, Y. Chen, D. Karl, E. Choy, D. C. Harmon, A. Kambadakone, D. Sahani, D. G. Duda, R. K. Jain, T. F. DeLaney
Journal: Journal of Clinical Oncology (2010)

10023 Background: Numerous preclinical studies demonstrate that anti-angiogenic agents increase the efficacy of radiation therapy (RT) against solid tumors. However, there have been no clinical studies of bevacizumab (BV) and RT (without chemotherapy) examining efficacy and biological effects. Methods: 20 pts with >5 cm, intermediate- or high-grade soft tissue sarcomas at increased risk of local recurrence (LR) received neoadjuvant BV and RT. Blood and tumor tissue were collected before treatment, after BV alone (for 2 wks), and after BV plus RT (for 6 wks). Serial perfusion CT scans assessed changes in tumor vasculature. Tumors were resected 6-7 wks following BV plus RT. Results: 13 extremity, 1 trunk, and 6 retroperitoneal tumors of varied histological subtypes were treated, and median tumor size was 8.25 cm. During treatment, there were no grade 4 toxicities, and 3 pts (15%) had grade 3 toxicities (hypertension, LFT elevation). Following surgery, 4 pts (20%) had major wound complications and one had a pulmonary embolism. Neoadjuvant BV plus RT resulted in 9 of 20 tumors (45%) with ≥80% necrosis, which is over double the historical rate with radiation alone. 3 pts had no viable tumor remaining. Microvessel density decreased from a mean of 20.7 to 9.7 (p=0.01) after BV alone and remained decreased following combination therapy (7.4). Following BV plus RT, tumor cell proliferation by PCNA immunohistochemistry decreased 53% (p=0.01), apoptosis by TUNEL immunohistochemistry increased 3.7 fold (p=0.02), and blood volume and permeability by perfusion CT decreased 63-64% (p<0.05). Oligonucleotide microarray analysis of untreated tumors revealed global differences in gene expression between responders and non- responders as well as an 8-gene signature that highly correlated with treatment response. Analysis of circulating proteins and cells is pending. After a median follow-up of 20 months, there was one local recurrence (5%). All pts declined adjuvant chemotherapy, and 7 pts (35%) developed metastatic disease. Conclusions: Bevacizumab appears to increase the efficacy of radiation therapy against soft tissue sarcomas and may reduce local recurrence. Gene signatures may be useful as biomarkers to predict response. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration AstraZeneca, Dyax, Millennium, SynDevRx SynDevRx Pfizer AstraZeneca, Dyax
A Randomized Phase 3 Study Comparing First-Line Docetaxel/Prednisone (Dp) to Dp Plus Custirsen in Men with Metastatic Castration-Resistant Prostate Cancer (Mcrpc)
Authors: K.N. Chi, C. Higano, J. Reeves, S. Feyerabend, G. Gravis, J. Ferrero, C. Jacobs, O. Barnett-Griness, A. Pande, J.S. de Bono
Journal: Annals of Oncology (2014)
Successful mobilization of peripheral blood stem cells (PBSCs) with AMD3100 in patients failing to collect with hematopoietic growth factors (HGF) and/or chemotherapy
Authors: A. Fassas, M. Fox, G. Calandra, G. Tricot
Journal: Journal of Clinical Oncology (2004)

6643 Background: Poor mobilization of PBSCs compromises the application of effective high-dose treatment (HDT) in multiple myeloma (MM). AMD3100, a reversible inhibitor of the binding of SDF-1α to CXCR4, may allow the collection of adequate PBSCs to support HDT in poor mobilizers. Methods: Ten MM pts (3 men, 7 women) with a median age of 60 (range: 52–70) years who had failed to mobilize ≥ 5 million CD34 cells/kg PBSCs, received a daily dose of AMD3100 (240 μg/Kg) approximately 10 hours prior to each apheresis, for up to 7 days. G-CSF (10 μg/Kg) was administered x 4 days prior to and concurrently with AMD3100 until completion of apheresis. Eight pts had <12 months of preceding conventional chemotherapy, and one received HDTx2 > 4 years earlier. Prior to AMD3100 administration, 14 attempts to collect PBSCs were performed following chemotherapy and HGF (n: 11) or HGF alone (n: 3) with a median of 0.19x106 CD34+/Kg (range: 0–2.94x106) collected per attempt. Only one patient had collected a >5x106 CD34+/Kg. All but 3 patients had normal platelet counts at the start of this trial. Results: All patients were leukapheresed for a median of 7 days (range: 3–7) and collected a median number of 2.55x106 CD34+/Kg (range: 0.74–8.04x106). An increase in absolute CD34 cells /μL was observed from a median of 1.6 (0.8 –4.5) prior to AMD3100 to 5.8 (2.3–29.7) 11 hours after the first dose of AMD3100 prior to the first PBSC collection. No grade IV non-hematologic toxicities were seen during mobilization. Four patients collected >5x106 CD34+/Kg, while a meaningful (>2.5x106/kg) number of CD34+ cells was achieved in 6 patients. In none of the AMD3100 collections were myeloma cells identified as measured by cIg/DNA flow cytometry (sensitivity<1%). HDT with AMD3100-collected PBSCs was administered to 1 patient. She achieved ANC>1000/μL on day +12. Conclusions: Clinically meaningful collections of PBSCs can be achieved with minimal toxicity in poor mobilizers after AMD3100 administration. However, poor mobilization with chemotherapy and/or HGF also appears to predict for poor, although seemingly better, collection with AMD3100. Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration AnorMED, Inc. AnorMED, Inc. AnorMED, Inc.
Bioluminescence evaluation of efficacy of oncolytic treatment with Newcastle disease virus (NDV) in malignant pleural mesothelioma
Authors: G. Silberhumer, P. Brader, J. Wong, D. Zamarin, I. Serganova, R. Blasberg, P. Palese, Y. Fong
Journal: Journal of Clinical Oncology (2009)

e14536 Background: Malignant pleural mesothelioma (MPM) is a highly aggressive tumor that arises from multipotent cells of the pleura. Chemotherapy and radiation have very limited therapeutic effects, and average survival time after diagnosis varies between 10 and 16 months. Immunotherapy, gene therapy (oncolytic viral therapy), and photodynamic therapy offer alternative treatment options, with promising results in animal studies. In the following study, the oncolytic efficacy of Newcastle disease virus (NDV(F3aa)-GFP) on MPM is tested and investigated by bioluminescence imaging. Methods: NDV(F3aa)-GFP was tested for viral cytotoxicity at different multiplicities of infection (MOI) against several mesothelioma cell lines in vitro by analyzing release of intracellular lactate dehydrogenase. For in vivo studies, MSTO 211H cells were transduced with firefly (Photinus pyralis) luciferase (FLuc)- encoding cDNAs (MSTO td 211H). Tumor-bearing animals (1e 7 cells injected intrapleurally) were treated with either single or multiple doses of NDV(F3aa)-GFP (1e 7 plaque-forming units) at different time points (days 1, 3, and 10) and followed by bioluminescence imaging. Results: Mesothelioma cell lines exhibited susceptibility to NDV lysis in the following order of sensitivity: MSTO 211H&gt;MSTO td 211H&gt;H-2452&gt;VAMT&gt;JMN. The cell lines H-2052, H-2373, and HMESO were not sensitive to viral treatment. In vivo studies with MSTO td 211H cells showed complete response to viral therapy in &gt;75% of the animals, resulting in eradication of tumor detected by bioluminescence imaging at day 10 after treatment. Control animals were sacrificed after 23 days due to tumor burden, while &gt;72% of the virally treated animals survived &gt;50 days after tumor injection. No signs of toxicity were observed in the treatment group. In addition, multiple treatment showed a significantly better response compared with single treatment (p=0.005). Conclusions: NDV appears to be an efficient viral oncolytic agent in therapy of malignant pleural mesothelioma in a murine model, and warrants further investigation as a potential therapeutic agent. No significant financial relationships to disclose.
Evolutionary conservation of human CD34+ Cell Endothelial Differentiation in the Zebrafish Embryo
Authors: O. Pozzoli, M. Lacovich, E. Siciliano, D. Avitabile, C. Lora Lamia, C. Gilardelli, E. Vigna, A. Biondi, M.C. Capogrossi, F. Cotelli, M. Pesce
Journal: Circulation (2007)
The incidence of bone pain with granulocyte colony stimulating factor (G-CSF) administration and the effect of hydroxyzine
Authors: S. Ogata, K. Ito, K. Kadoike, T. Egawa, Y. Kinugasa, M. Kozuki
Journal: Journal of Clinical Oncology (2005)

8242 Background: The bone pain frequently emerges as one of the side effects of G-CSF administration. Rising pressure within bone marrow by increased granulocytes, edema within bone marrow by histamine release, and increased level of bradykinin are thought to be the mechanisms underlying it. The incidence of bone pain is reported to be 1–5% of all cases, but in practice we have the impression that there have been more cases with bone pain, some of which are resistant to treatment with non-steroid anti-inflammatory drugs (NSAIDs). So we reexamined the incidence of bone pain with G-CSF and the analgesic effect of hydroxyzine. Methods: 1) We sent out questionnaires about the presence of bone pain and its details to patients who are administered G-CSF in the past and analyzed those answers, retrospectively. 2) Prospectively since 2003, we administered NSAIDs or hydroxyzine (50mg b.i.d.) to patients with bone pain after G-CSF administration and examined its analgesic effect. With next G-CSF administration in those patients, we administered hydroxyzine beforehand, and checked its preventive effect. Results: 1) The incidence of bone pain with G-CSF administration was 10% (2 cases in 20 patients) by questionnaires, retrospectively. 2) Prospectively, 40 patients were administrated G-CSF by neutropenia since 2003. In 4 cases with bone pain after G-CSF administration, NSAIDs were ineffective, but hydroxyzine was effective in such cases. The preventive administration of hydroxyzine suppressed the pain. Conclusions: The incidence of bone pain with G-CSF may be higher clinically than reported before. Hydroxyzine is effective to the bone pain, and it also protects against the onset of the bone pain. No significant financial relationships to disclose.
Durability and complication rates of arm-sited central venous access ports (CVAPs) versus chest-sited CVAPs for chemotherapy administration at a rural Australian centre
Authors: A. J. Weickhardt, G. Chong, S. Shea, D. Arhanghelschi, K. Hamilton
Journal: Journal of Clinical Oncology (2008)

20643 Background: CVAPs are required to deliver infused chemotherapy regimens for patients with poor peripheral venous access. Arm-sited CVAPs are implanted subcutaneously 10–15 mm above the cubital fossa where the basilic vein is cannulated. They do not require subcutaneous tunnelling, avoid chest surgical scars and are an alternative to traditional chest-sited CVAPs. We compared the durability and complication rates of radiologically inserted arm CVAPs to surgically inserted chest CVAPs used to deliver chemotherapy. Methods: A retrospective, single institution analysis was performed of all patients (pts) who had a chest CVAP inserted for chemotherapy over a 30-month period, and compared to pts who had an arm CVAP over the following 30-month period, with minimum follow-up of 6 months. The primary endpoint was successful use of the CVAP, defined as completion of planned chemotherapy without a complication prompting removal of the CVAP. Results: 49 pts had a chest CVAP (Bard) (median age 59, median insertion duration 277 days). 85 pts had an arm CVAP (Cook) (median age 58, median duration insertion 281 days). The two most common cancers were colorectal (43% of chest CVAPs, 42% of arm CVAPs) and breast (29% of chest CVAPs, 40% of arm CVAPs). The primary endpoint was achieved by most pts, and there was no significant difference between chest and arm CVAPs (92% vs 88%, p=0.242). Infection and thombosis were the major complications that forced removal of CVAPs. The infection rate for chest and arm CVAPS was 6% vs 8% (0.16 vs 0.28 per 1,000 days) and the rate of thrombosis was 6% vs 2% (0.16 vs 0.08 per 1,000 day). 12% of chest CVAPs were removed with a complication at any stage compared with 15% of arm CVAPs (p=0.248). These rates are comparable to those seen in other studies of arm and chest CVAPs. Conclusions: Arm CVAPs appear to be equivalent in durability and complications compared to chest CVAPs for chemotherapy administration in a rural setting. In addition, they may be cosmetically preferable and convenient to insert. No significant financial relationships to disclose.
Second-line chemotherapy with mitomycin C and S-1 in patients with advanced gastric cancer
Authors: D. Shin, S. Lee, S. Park, S. Bang, E. Cho, J. Lee
Journal: Journal of Clinical Oncology (2006)

14083 Background: S-1, a fourth generation oral fluoropyrimidine that mimics infusional 5-fluorouracil, has demonstrated activity against advanced gastric cancer. Based on a single agent activity and in vitro synergy between mitomycin C (MMC) and 5-fluorouracil, we conducted a phase II study to assess the efficacy and tolerability of the combination of S-1 and MMC as second-line chemotherapy for previously treated, advanced gastric cancer. Methods: Patients with measurable gastric cancer, progressive after at least one prior chemotherapy for metastatic disease, were treated with MMC 7 mg/m 2 on day 1 and S-1 40 mg/m 2 twice daily as an intermittent regimen of 4 weeks of treatment followed by a 2-week rest. Treatment was repeated every 6 weeks, for up to 4 cycles. Objective response rate was the primary endpoint and was evaluated every 2 cycles of chemotherapy. With a single-stage phase II design, at least 25 patients were required. Results: Of the 26 patients registered, 24 patients were evaluable for response and 26 for safety. Eighteen patients (69%) were previously treated with 5-fluorouracil-based chemotherapy, and 10 (39%) were treated with taxanes. The patients’ median age was 55 years (range, 38–73) and 7 (27%) had an ECOG performance status of 2. A total of 64 chemotherapy cycles were delivered (median, 2; range, 1–4). In an intent-to-treat analysis, 6 patients (23%) achieved a partial response, which maintained for 3.5 months. The median progression-free and overall survivals were 4.4 months (95% CI, 1.7–7.2) and 5.4 months (95% CI, 3.4–7.4), respectively. Major toxic effects included stomatitis, diarrhea and fatigue, but were generally mild and manageable. No patient developed hemolytic reaction. Conclusions: Second-line chemotherapy with MMC and S-1 is an effective regimen for advanced gastric cancer with an acceptable toxicity profile and a convenient administration schedule. No significant financial relationships to disclose.
Absence of hypodiploidy and/or chromosome 13 abnormalities (hypo-CA13) confers superior survival in multiple myeloma (MM) patients (pts): Interim analysis of total therapy (TT) II trial
Authors: A. B. T. Fassas, J. Sawyer, J. McCoy, E. J. Anaissie, C. K. Lee, G. Talamo, C. Wendling, M. Zangari, F. Van Rhee, R. Thertulien, G. J. Tricot, B. Barlogie
Journal: Blood (2003)
Characteristics of efficacy evidence supporting approval of supplemental indications for prescription drugs in United States, 2005-14: systematic review
Authors: Bo Wang, Aaron S Kesselheim
Journal: BMJ (2015)

To characterize the types of comparators and endpoints used in efficacy trials for approvals of supplemental indications, compared with the data supporting these drugs' originally approved indications.Systematic review.Publicly accessible data on supplemental indications approved by the US Food and Drug Administration from 2005 to 2014.Types of comparators (active, placebo, historical, none) and endpoints (clinical outcomes, clinical scales, surrogate) in the efficacy trials for these drugs' supplemental and original indication approvals.The cohort included 295 supplemental indications. Thirty per cent (41/136) of supplemental approvals for new indications were supported by efficacy trials with active comparators, compared with 51% (47/93) of modified use approvals and 11% (7/65) of approvals expanding the patient population (P<0.001), almost all of which related to pediatric patients (61/65; 94%). Trials using clinical outcome endpoints led to approval for 32% (44/137) of supplemental approvals for new indications, 30% (28/93) of modified indication approvals, and 22% (14/65) of expanded population approvals (P=0.29). Orphan drugs had supplemental approvals for 40 non-orphan indications, which were supported by similar proportions of trials using active comparators (28% (11/40) for non-orphan supplemental indications versus 24% (10/42) for original orphan indications; P=0.70) and clinical outcome endpoints (25% (10/40) versus 31% (13/42); P=0.55).Wide variations were seen in the evidence supporting approval of supplemental indications, with the fewest active comparators and clinical outcome endpoints used in trials leading to supplemental approvals that expanded the patient population.
Influence of psychosocial consultation with comprehensive psychosocial assessment (CPA) on identifying difficulties in cancer patients.
Authors: J. J. Lee, G. Lee, S. Chin, S. Lee, Y. Kim, I. Choi
Journal: Journal of Clinical Oncology (2010)

e19680 Background: The assessment of cancer patient's psychosocial difficulty is considered as the sixth vital sign with increasing overall survival and drugs cost. We evaluated the contributory factors to investigate the psychosocial difficulties and to determine the referral to the social worker in cancer patients. Methods: We prospectively conducted the study in a single institute from February to December 2009. We investigated patient's characteristics, seven questionnaires, including financial problem, information of social system, personal care problem, psychological problem, and rehabilitation problem and their overall need of consultation. Results: A total of 95 patients were enrolled and 93 patients had a interview with the social worker. The median age was 58 years and male was 65%. The common diseases were lung cancer and gastrointestinal cancer. Two-thirds was stage IV and in the course of chemotherapy. PE ECOG 2-3 was 35% and pain VAS 0-3 was 71%. High education over high school was 53%. 80% of the patients have got married. 88% of patients visited the hospital via outpatient clinic. Patient with keeping job was 27%. The most common needs were to know the social system (90%), to solve the financial (74%), and personal care problem (70%) according to patients but the social system (96%), financial (65%), and psychological problem (47%) according to physician. The agreement of the financial problem was highest (Kappa coefficient, 0.212, p = 0.035) between patients and physician. 2 or more of total count was significantly correlated with their overall need (R = 0.434, p<0.0001). With the referral, 26%, 37% and 34% of patients benefit from support, interview or intervention in terms of financial problem, the benefit of social system and psychosocial problem, respectively. Conclusions: More than 90% of patients wanted to solve the psycjosocial problem. With the CPA, more than a third patients benefited. The assessment of the psychosocial difficulty should be considered as the sixth vital sign and be evaluated to identify the contributory factors in cancer patients for improving the quality of life. No significant financial relationships to disclose.