tbuckley/cabot-search huggingface dataset:
Diagnosis of gastric submucosal tumors using endoscopic ultrasound guided fine needle aspiration
Authors: A. Sawaki, N. Mizuno, N. Hoki, T. Takagi, T. Nakamura, M. Tajika, H. Kawaki, R. Takayama, Y. Takeda, K. Yamao
Journal: Journal of Clinical Oncology (2008)

4574 Background: Submucosal lesions are incidentally detected on barium meal study or endoscopy. The differential diagnosis of them includes a variety of neoplasms, inflammation, and extraluminal compression. Since conventional endoscopic biopsy is superficial, the diagnostic yield of submucosal tumors (SMTs) covered with normal mucosa remains low. Intraluminal biopsy is required for preventing dissemination and endoscopic ultrasound guided fine needle aspiration (EUS-FNA) has reported as effective modality. The purpose of this study is to evaluate the diagnosis of gastric SMTs using EUS-FNA. Methods: A total of 304 consecutive patients with gastric submucosal lesions were examined by EUS between 1997 and 2006. 97 out of 294 cases underwent EUS-FNA. The materials obtained from the EUS-FNA were stained with the rapid Romanowsky for cytological examination. Immunohistochemical staining was performed for the final diagnosis of GIST. Results: Of the 304 cases, 119 were finally diagnosed by EUS: extraluminal compressions due to adjacent viscera were found in 33 cases and normal in 29, intraluminal lesions diagnosed as heterogenic pancreas in 42, lipoma in 7 and cyst in 8. The remaining 185 out of 304 cases were diagnosed as SMTs and 97 cases underwent EUS-FNA because of tumor size more than 2cm, patient’s request or malignant findings of EUS. The majority of SMTs examined with EUS-FNA was gastrointestinal stromal tumors (n=52), followed by spindle cell tumor (n=13), inflammatory tumor (n=5), gastric cancer (n=5), heterogenic pancreas (n=4), cyst (n=2), myogenic tumor (n=2), neurogenic tumor (n=2), carcinoid (n=1), Glomus (n=1) and undiagnosed (n=10). The diagnostic yield of EUS and EUS-FNA in gastric lesions was 39.1% and 89.7%, respectively. Conclusions: The majority of gastric SMTs was gastrointestinal stromal tumor. Around 60% of 97 cases underwent EUS-FNA was malignant tumors. EUS-FNA is highly diagnostic yield in gastric SMT, and very useful for patients with failure of previous EUS or endoscopic forceps biopsy to obtain a final diagnosis. No significant financial relationships to disclose.
Rituximab, methotrexate (MTX), procarbazine, and vincristine (R-MPV) followed by consolidation high-dose chemotherapy (HDC) and autologous stem-cell transplant (ASCT) for newly diagnosed primary CNS lymphoma (PCNSL).
Authors: Antonio Marcilio Padula Omuro, Denise Correa, Craig Moskowitz, Matthew J. Matasar, Lisa Marie DeAngelis, Thomas Joseph Kaley, Igor T. Gavrilovic, Craig Nolan, Elena Pentsova, Christian Grommes, Lauren E. Abrey, Craig Steven Sauter
Journal: Journal of Clinical Oncology (2012)

2008 Background: In our previous study in newly diagnosed PCNSL, induction chemotherapy with MTX and cytarabine followed by consolidation HDC (carmustine, etoposide, cytarabine, melphalan [BEAM]) with ASCT without radiotherapy resulted in only 50% of pts transplanted, reflecting low efficacy of induction chemotherapy, and short intent-to-treat (ITT) median PFS (=6m). In this phase II trial, we sought to optimize this strategy by utilizing a more effective induction regimen (R-MPV) and a more aggressive HDC regimen (Soussain et al). Methods: Pts received 5-7 cycles of R-MPV (MTX: 3.5g/m2) and if a partial or complete response was achieved, HDC with thiothepa, cyclophosphamide and busulfan was given, followed by ASCT and no radiotherapy. The primary endpoint was ITT 1 year event-free survival (promising: 75%, non-promising: 50%; 90% power, significance=0.05). Follow-up included comprehensive neuropsychological evaluation. Results: Accrual has been completed (N=32 pts, median age 57 [range 23-67], median KPS=80). Following R-MPV, 17 pts achieved a CR, 13 pts a PR and two pts progressed. A total of 25 (78%) pts were transplanted; the reasons for not receiving transplant were progressive disease (N=2), poor performance status/ physician’s decision (N= 2), mobilization failure (N=1) and consent withdrawn (N= 2). One pt who withdrew consent relapsed and received HDCASCT for salvage. Two (8%) pts died from early complications of ASCT (Stevens-Johnson: one, sepsis: one) and one pt experienced a fatal late colitis of unknown etiology. In the ITT population, the median EFS and OS have not been reached after a median follow-up of 22 months. The 1 year EFS was 78% (95%CI 58-90) and the 2y OS was 76% (95% CI 54-89). No pt has developed delayed neurotoxicity. Conclusions: R-MPV induction regimen resulted in improved response rates, allowing 78% of pts to receive HDC-ASCT. Although more toxic, this regimen resulted in excellent disease control and survival in the ITT population, far exceeding the efficacy of our previous transplant study. The primary endpoint was met, warranting further investigation.
Percutaneous Intervention for Concurrent Chronic Total Occlusions in Patients With STEMI
Authors: José P.S. Henriques, Loes P. Hoebers, Truls Råmunddal, Peep Laanmets, Erlend Eriksen, Matthijs Bax, Dan Ioanes, Maarten J. Suttorp, Bradley H. Strauss, Emanuele Barbato, Robin Nijveldt, Albert C. van Rossum, Koen M. Marques, Joëlle Elias, Ivo M. van Dongen, Bimmer E.P.M. Claessen, Jan G. Tijssen, René J. van der Schaaf, Jose P.S. Henriques, Rene van der Schaaf, Jan G.P. Tijssen, Felix Zijlstra, Menko-Jan de Boer, Rolf Michels, Martijn Meuwissen, Pierfrancesco Agostoni, K. Gert van Houwelingen, Hein J. Verberne, Alexander Hirsch, José P.S. Henriques, Jan J. Piek, Robbert J. de Winter, Karel T. Koch, Marije M. Vis, Jan Baan, Joanna Wykrzykowska, Truls Råmunddal, Dan Ioanes, Peep Laanmets, René J. van der Schaaf, Ton Slagboom, Giovanni Amoroso, Erlend Eriksen, Vegard Tuseth, Matthijs Bax, Carl E. Schotborgh, Maarten J. Suttorp, Bradley H. Strauss, Emanuele Barbato, Koen M. Marques, Olivier Bertrand, Martijn Meuwissen, Martin van der Ent, Jacques Koolen
Journal: Journal of the American College of Cardiology (2016)
TM-233 Exerts Anti-Myeloma Activity and Overcomes Bortezomib-Resistance In Human Multiple Myeloma Cells By Targeting NF-κB and JAK/STAT Dual-Signaling Pathways
Authors: Morihiko Sagawa, Tatsuki Tomikawa, Tomoe Anan, Takayuki Tabayashi, Reiko Watanabe, Michihide Tokuhira, Masaki Ri, Yuichi Hashimoto, Shinsuke Iida, Masahiro Kizaki
Journal: Blood (2013)
Non-invasive epicutaneous vaccine against Respiratory Syncytial Virus: Preclinical proof of concept
Authors: Pierre-Louis Hervé, Delphyne Descamps, Charlotte Deloizy, Véronique Dhelft, Daphné Laubreton, Edwige Bouguyon, Abdelhak Boukadiri, Catherine Dubuquoy, Thibaut Larcher, Pierre-Henri Benhamou, Jean-François Eléouët, Nicolas Bertho, Lucie Mondoulet, Sabine Riffault
Journal: Journal of Controlled Release (2016)

To put a Respiratory Syncytial Virus (RSV) vaccine onto the market, new vaccination strategies combining scientific and technical innovations need to be explored. Such a vaccine would also need to be adapted to the vaccination of young children that are the principal victims of acute RSV infection. In the present project, we describe the development and the preclinical evaluation of an original epicutaneous RSV vaccine that combines two technologies: Viaskin® epicutaneous patches as a delivery platform and RSV N-nanorings (N) as a subunit antigen. Such a needle-free vaccine may have a better acceptability for the vaccination of sensible population such as infants since it does not require any skin preparation. Moreover, this self-applicative vaccine would overcome some issues associated to injectable vaccines such as the requirement of sterile medical devices, the need of skilled health-care professionals and the necessity of stringent store conditions. Here, we demonstrate that Viaskin® patches loaded with a formulation containing N-nanorings (Viaskin®-N) are highly immunogenic in mice and promotes a Th1/Th17 oriented immune response. More importantly, Viaskin®-N epicutaneous vaccine confers a high level of protection against viral replication upon RSV challenge in mice, without exacerbating clinical symptoms. In swine, which provides the best experimental model for the transcutaneous passage of drug/antigen in human skin, we have shown that GFP fluorescent N-nanorings, delivered epicutaneously with Viaskin® patches, are taken up by epidermal Langerhans cells. We have also demonstrated that Viaskin®-N induced a significant RSV N-specific T-cell response in pig. In conclusion, Viaskin®-N epicutaneous vaccine seems efficient to protect against RSV infection in animal model.
5-Fluorouracil, folinic acid and oxaliplatin (FOLFOX) in poor prognosis patients with metastatic colorectal cancer
Authors: C. Tournigand, T. Andre, I. Chirivella, A. Figer, G. Lledo, M. Flesch, J. R. Mel Lorenzo, E. Achille, B. Landi, M. Hebbar
Journal: Journal of Clinical Oncology (2004)

3565 Background: High alkaline phosphatases (Alk Ph) level is an adverse prognostic factor in patients (pts) with metastatic colo-rectal cancer (CRC). Pts with Alk Ph level over 3-time the upper normal value (UNV) were excluded from previous studies. OPTIMOX trial consisted in a phase III study for pts with conventional inclusion criteria (526 pts), comparing FOLFOX4 to FOLFOX7 x 6 cycles, followed simplified LV5FU2 x 12 cycles and FOLFOX7 reintroduction; and two exploratory studies in pts > 75 yrs (37 pts) and in pts with Alk Ph level > 3-time the UNV (63 pts), treated according to the same regimens. Methods: This report concerns the tolerance and the efficacy observed for the 63 pts with an initial Alk Ph level over 3-time the UNV. 33 pts were treated with FOLFOX4 (arm A), and 30 with FOLFOX7 - sLV5FU2 - FOLFOX7 (arm B). Characteristics of these pts were : PS 0/1–2=26/74%, median age 63 yrs; LDH (normal / > normal) 6%/94%, metastatic site (1/ > 1) 70/30%. Results: 60 pts (766 cycles) and 54 pts are evaluable for safety and response, respectively. 2 pts benefited from metastasis removal. Grade 3–4 toxicities (% of pts, arm A / arm B) were: neutrophils 15.2/10.0, platelets 9.1/3.3, hemoglobin 9.1/3.3, nausea-vomiting 0/10.0, diarrhea 6.1/6.7, neurotoxicity 9.1/10.0. Maximal toxicity per patient was grade 3–4 in 42.4% of arm A pts, and 33.4% of arm B pts. Response rate (intent-to-treat) was 55.6 % (arm A 48.5%; arm B 63.3%). Median PFS was 28 weeks (arm A 29 w; arm B 28 w) and median OS was 50 weeks (arm A 61w and arm B 48 w). Conclusion: These safety and efficacy results incite to propose FOLFOX regimens (either FOLFOX4 or FOLFOX7) in poor prognosis pts with metastatic colorectal cancer. No significant financial relationships to disclose.
Erythropoiesis stimulating agents (ESAs): An overview of safety-related findings from the Research on Adverse Drug Events and Reports (RADAR) project
Authors: J. M. McKoy, A. O. Sartor, M. Henke, D. P. West, D. M. Courtney, K. R. Carson, B. J. Edwards, A. T. Samaras, C. L. Bennett
Journal: Journal of Clinical Oncology (2008)

6635 Background: ESAs were approved in 1989 and 1993 for treatment of anemia associated with chronic kidney disease (CKD) or chemotherapy-associated anemia, respectively. Since then, clinicians have viewed ESAs as having little toxicity. Methods: We reviewed case studies and epidemiologic assessments of relative risks (RR) and hazard rates (HR) of ESA-associated toxicity in the setting of CKD and cancer. Data sources included meta-analyses, randomized clinical trials, and FDA MedWatch reports. Results and Conclusions: While safety signals for ESA-associated toxicity were first reported in 1998 (Besarab et al; the Normal Hematocrit Trial), most serious ESA- associated toxicities were not reported until 2002 or later- 13 years after epoetin first received FDA approval. Pharmacovigilance efforts require commitment to conduct focused long-term safety studies especially when commonly used drugs have small RR for toxicity/death. Toxicity Setting # of Cases/Rates Reference Cardiovascular toxicity CKD RR=1.24 NEJM1998 Pure Red Cell Aplasia CKD 191/4.5 per 10,000 (Eprex) NEJM2002 NEJM 2005 Tumor Progression Anemia of Ca RR=1.39 Lancet 2003 Counterfeit Drug Cancer n=7/RR not known ASH 2005 Venous thromboembolism All cancers n=172/760 per 10,000 JNCI 2005 Venous thromboembolism Myeloma n=20/2,300 per 10,000 NEJM 2005 Gadolinium Nephrogenic Systemic Fibrosis CKD 22/RR not known Annals 2006 Mortality CKD RR= 1.29 Lancet 2007 Mortality Anemia of Ca RR=1.39 NEJM 2007 Mortality Ca-associated anemia RR= 1.39 Lancet 2007 Locoregional progression Head/neck Ca RR= 1.69 NA Leukemic transformation Primary myelofibrosis n=22/HR =3.1 ASH 2007 Mortality Cancer/CKD RR = 1.3 (cancer); 1.3 (CKD) ASH 2007 JAMA 2008 No significant financial relationships to disclose.
Validation of the Simplified Psoriasis Index in Dutch children and adolescents with plaque psoriasis
Authors: M.J. van Geel, M.E. Otero, E.M.G.J. de Jong, P.C.M. van de Kerkhof, M.M.B. Seyger
Journal: British Journal of Dermatology (2016)

The Simplified Psoriasis Index (SPI) is a three‐domain assessment measure for psoriasis, including separate indicators of current severity (SPI‐s), psychosocial impact (SPI‐p), and past history and interventions (SPI‐i). There are two complementary versions available designed for completion by a health professional (proSPI) or by patient self‐assessment (saSPI). The validity and reliability of the proSPI vs. saSPI have already been demonstrated in adults. To date, validated severity measures for paediatric psoriasis do not exist. To validate the current severity (SPI‐s) and psychosocial impact (SPI‐p) domains of the proSPI and saSPI in children and adolescents with psoriasis. All patients aged < 18 years with plaque psoriasis visiting the dermatology outpatient department of Radboud University Medical Center, the Netherlands, between September 2013 and April 2014 were asked to complete Dutch versions of the saSPI and the Children's Dermatology Life Quality Index (CDLQI). The original English versions of the proSPI and Psoriasis Area and Severity Index (PASI) were completed by the physician at the same visit. In total, 113 patients (median age 12·0 years, range 4–17) were included. There was a close correlation between the proSPI‐s and PASI (r = 0·87), which was higher than between the saSPI‐s and PASI (r = 0·69). The correlation between the SPI‐p and CDLQI was 0·78. The full range of scores was utilized in both proSPI‐s and SPI‐p, although the highest saSPI‐s score was 30 (maximum 50). In paediatric psoriasis, the proSPI and saSPI are shown to be valid and usable. The SPI‐s and SPI‐p can be readily introduced into routine clinical practice.
Phase II randomized study of nab-paclitaxel versus conventional paclitaxel as first-line therapy of metastatic HER2-negative breast cancer for neurotoxicity characterization: An Oncosur Study Group study.
Authors: Eva Ciruelos, Noelia Martinez, Blanca Cantos, Maria Jose Echarri, Santos Enrech, Coralia Bueno, Juan Antonio Guerra, Luis Manso, Tomas Pascual, Cesar Mendiola, Cristina Dominguez, Juan Francisco Gonzalo, Cristina Rodriguez de Antona, Maria Apellaniz-Ruiz, Juan Luis Sanz, Juan Manuel Sepúlveda
Journal: Journal of Clinical Oncology (2015)

1029 Background: Nab-paclitaxel (Nab-P) is a nanoparticle albumin-bound form of paclitaxel commonly used in various tumor types. Its main toxicity is neuropathy; however, it has not been clinically and physiologically characterized properly. Methods: 1st-line patients (pt) with confirmed HER2-negative metastatic breast cancer were treated with: A) conventional P 80 mg/m2 on days 1, 8 and 15; B) Nab-P 100 mg/m2 on days 1, 8 and 15; C) Nab-P 150 mg/m2 on days 1, 8 and 15; D) Nab-P 150 mg/m2 on days 1 and 15, in 28-day cycles. Primary objective: characterize neurotoxicity according to Total Neuropathy Score (TNS) and electromyographic changes. Secondary objectives: rate of induced NP, pharmacogenetic study for NP, activity, toxicity profile and QoL. Results: Sixty pt included from Jan 2013 until Jul 2014 in 7 centers. Median age: 59 (37-84); main sites of mets: liver (60%), bone (42%), and lung (23%). Sixteen (27%) pt stage IV at diagnosis; 52 (87%) received prior adjuvant CT (52% anthracyclines, 35% taxanes). Twelve pt remain on therapy (median 6 cycles), while 48 pt stopped treatment mainly due to disease progression (20 pt) or toxicity (17 pt, 13 NP). Most common AEs (all grades) per pt: asthenia (62%), NP (75%), alopecia (30%), neutropenia (23%) and nail toxicity (28%). Forty five pt had NP: 20 G1 (4 pt A, 6 pt B, 3 pt C, 7 pt D), 18 G2 (4 pt A, 6 pt B, 4 pt C, 4 pt D) and 7 G3 (1 pt A, 6 pt C). Median time to develop grade > 1 NP was 8.8 months (4 months in arm C; NR arms A and D). TNS scores showed a rapid deterioration in first assessments followed by a plateau. At current follow up, changes in TNS and toxicity were not statistically different between arms. Concerning genetic variants, the strongest association to NP risk corresponded to EPHA5-rs7349683. Conclusions: Median time to development of significant NP was longer than expected, except for higher Nab-P doses (arm C). No stat. differences in NP rates were observed (small simple size); numerically arm C had higher risk of G3 NP. EPHA-rs7349683 SNP is associated with higher NP risk. Detailed genomic data and EMG results will be presented. Clinical trial information: NCT01763710.
Successful Treatment of Refractory Pityriasis Rubra Pilaris With Secukinumab
Authors: Daniel Schuster, Andrea Pfister-Wartha, Leena Bruckner-Tuderman, Christoph M. Schempp
Journal: JAMA Dermatology (2016)

Discussion | The results of this study reveal important differences in the microbiota of HS lesions in obese vs nonobese patients.Gut flora alterations are seen in obese patients, 4,5 and HS has been associated with obesity.It is possible that altered gut or skin flora could have a pathogenic role in HS.Some of the limitations of the present study include the use of retrospective data and the lack of a control group consisting of patients with no history of HS.Although these cultures were obtained from purulence extruding from HS lesions, the bacterial culture results could represent skin or gut flora contamination.Information about the specific anatomic locations of HS cultures was not available.Because only the first recorded culture of each patient was analyzed, it is unknown if the culture results would change with time and further antibiotic therapy.The use of data obtained from swabbased cultures may also represent a potential limitation because DNA-based approaches to microbial analysis may yield more information and lead to identification of organisms that are not cultivable.The use of more advanced microbiome techniques may be an important consideration for future studies.These data indicate that further research is needed to elucidate the role of specific bacterial species in the pathogenesis of HS and may suggest a role for targeted treatment of specific bacterial species in this disorder.
Dendritic cells maintain dermal adipose–derived stromal cells in skin fibrosis
Authors: Jennifer J. Chia, Tong Zhu, Susan Chyou, Dragos C. Dasoveanu, Camila Carballo, Sha Tian, Cynthia M. Magro, Scott Rodeo, Robert F. Spiera, Nancy H. Ruddle, Timothy E. McGraw, Jeffrey L. Browning, Robert Lafyatis, Jessica K. Gordon, Theresa T. Lu
Journal: Journal of Clinical Investigation (2016)

Scleroderma is a group of skin-fibrosing diseases for which there are no effective treatments. A feature of the skin fibrosis typical of scleroderma is atrophy of the dermal white adipose tissue (DWAT). Adipose tissue contains adipose-derived mesenchymal stromal cells (ADSCs) that have regenerative and reparative functions; however, whether DWAT atrophy in fibrosis is accompanied by ADSC loss is poorly understood, as are the mechanisms that might maintain ADSC survival in fibrotic skin. Here, we have shown that DWAT ADSC numbers were reduced, likely because of cell death, in 2 murine models of scleroderma skin fibrosis. The remaining ADSCs showed a partial dependence on dendritic cells (DCs) for survival. Lymphotoxin β (LTβ) expression in DCs maintained ADSC survival in fibrotic skin by activating an LTβ receptor/β1 integrin (LTβR/β1 integrin) pathway on ADSCs. Stimulation of LTβR augmented the engraftment of therapeutically injected ADSCs, which was associated with reductions in skin fibrosis and improved skin function. These findings provide insight into the effects of skin fibrosis on DWAT ADSCs, identify a DC-ADSC survival axis in fibrotic skin, and suggest an approach for improving mesenchymal stromal cell therapy in scleroderma and other diseases.
P1.42 (also presented as PD2.04): PEM/CBP/BEV Followed by Maintenance PEM/BEV in Hispanic Patients With NSCLC: Outcomes According to TS, ERCC1 and VEGF
Authors: Leonardo Rojas, Andrés F. Cardona, Oscar Arrieta, Beatriz Wills, Luis Corrales-Rodriguez, Hernán Carranza, Carlos Vargas, Jorge Otero, Claudio Martin, Mauricio Cuello, Carlos Ortiz, Rafael Rosell
Journal: Journal of Thoracic Oncology (2016)
Proof of mechanism (POM) in the first-in-human trial of two novel indenoisoquinoline, non-camptothecin topoisomerase I (TOP1) inhibitors.
Authors: James H. Doroshow, Jiuping Jay Ji, Alice Chen, Deborah Allen, Yiping Zhang, Scott M Lawrence, Thomas D. Pfister, Lihua Wang, Christophe E. Redon, William Bonner, Giovanna Speranza, Marcie K. Weil, Julie Eiseman, Julianne L. Holleran, Robert J. Kinders, Jan Hendrik Beumer, Ralph E. Parchment, Yves Pommier, Joseph E. Tomaszewski, Shivaani Kummar
Journal: Journal of Clinical Oncology (2012)

3031 Background: Indenoisoquinolines LMP 400 and LMP 776 form stable DNA-top1 cleavage complexes, have a preference for unique DNA cleavage sites, and are not substrates for ABC transporters compared to camptothecins. We conducted a randomized phase I trial of LMP 400 and LMP 776 in patients (pts) with refractory tumors to establish safety and MTD of LMP 400 and LMP 776 administered IV daily x 5 d, q 28d; determine PK; evaluate TOP1 and γH2AX levels in tumor biopsies (bx); and compare pharmacodynamic responses of LMP400 and LMP776. Methods: Pts had refractory malignancies; ≥ 18 yrs old; KPS &gt; 70%; adequate organ function. DLT: drug-related gr ≥ 3 non-hem or gr 4 hem toxicities during C1. Pts assigned to receive either LMP 400 or LMP 776. Dose level (DL) in mg/m 2 /day for LMP 776: 1, 2, 3, 4.5 mg; LMP 400: 2.5, 5, 10, 20, 40, 80. Accelerated titration design with one pt per dose level (DL), 100% dose escalation until one DLT or 2 gr 2 toxicities, then 3+3 design. Tumor bx and circulating tumor cells (CTCs) were obtained at baseline and C1D3. Results: Twenty pts accrued to date [LMP 400 (11 pts); LMP 776 (9 pts)]; M/F 7/13; median age 59 (range 32-71 yrs); diagnosis (# of pts): colorectal (10), vaginal adenocarcinoma (1), head and neck (2), bladder (1), melanoma (1), pancreas (1), thyroid (1), small cell lung (1), sarcoma (1), lymphoma (1). DLTs: LMP 400- gr 4 myelosuppression, gr 3 fatigue at DL 6; DL 5 expanded to establish MTD; LMP 776 (DL2)- gr 4 hypercalcemia, no other DLTs, dose escalation continuing. One pt with irinotecan-refractory colon cancer had shrinkage of lung nodules post one cycle of LMP 400. Relative to baseline, 5 of 6 tumor bx demonstrated 20-50% reduction in TOP1 levels (LMP 776); an increase in γH2AX foci in tumor was observed in 2/6 LMP 776 and 1/1 LMP 400 pts. An increase in γH2AX was also observed in hair bulbs (3/3 pts) and CTCs (9/20 pts). PK for LMP 400 and LMP 776: mean T1/2 48 and 36 h; Cl 1.5 and 2.0 L/h/m 2 ; Vc 30 and 31 L/m 2 , respectively. Conclusions: POM, as assessed by reduction in TOP 1 levels and increase in γH2AX in tumor and CTCs, and preliminary evidence of activity, has been demonstrated in this first-in-human trial of indenoisoquinoline-class of TOP1 inhibitors. Accrual is ongoing.