tbuckley/cabot-search huggingface dataset:
Durable remissions after rituximab plus thalidomide for relapsed/refractory mantle cell lymphoma
Authors: J. Drach, H. Kaufmann, S. Woehrer, A. Chott, C. C. Zielinski, M. Raderer
Journal: Journal of Clinical Oncology (2004)

6583 Background: Mantle cell lymphoma (MCL) remains difficult to treat by conventional treatment approaches. Since the microenvironment plays an important role for growth and survival of malignant B-cells, we hypothesized that a treatment strategy targeting both the tumor cell and the microenvironment could be active in MCL. Methods: A phase 2 clinical trial was performed to evaluate the toxicity and efficacy of rituximab plus thalidomide (R+THAL) in patients (pts) with CD20 positive relapsed MCL (previously treated by CHOP or a CHOP-like regimen). R was administered at 375 mg/m2 on days 1, 8, 15, and 22; THAL was given at a daily dose of 200mg starting on day 1 and a dose escalation to 400mg on day 15 (continued until progression or relapse). Results: 16 pts with MCL were treated (8 pts at first relapse including 2 pts after autologous transplantation, 5 pts at ≥ second relapse, 1 pt with primary CHOP-resistant MCL). Median age of pts was 67 (range, 45 to 76) years, and time from initial diagnosis ranged between 6 and 53 (median, 21) months. According to the IPI, 8 pts were at intermediate-high or high risk. In 7 pts, grade 2 fever and chills (grade 1–2) associated with administration of R were observed. Side effects of THAL (mild to moderate) included fatigue, constipation, and peripheral neuropathy. One pt experienced severe neutropenia associated with THAL causing discontinuation of treatment, and thromboembolic events were observed in 2 pts. 13 of the 16 pts experienced an objective response (5 CR including the pt who failed to respond to CHOP and one pt at relapse after autotransplantation; 8 PR), one pt had SD. Tumor responses occured both at nodular and extranodular MCL manifestations. Median time to progression (TTP) was 20 months. In pts achieving a CR, TTP was longer than the preceding TTP after chemotherapy (27+, 21, 20, 29 months versus 3, 15, 17, 22 months, respectively). Conclusions: R+THAL has marked anti-tumor activity and low toxicity in pts with relapsed/resistant MCL, even after high-dose therapy. Thus, a clinical trial with R-CHOP-THAL as frontline therapy for pts with MCL has been initiated. No significant financial relationships to disclose.
A Novel Orally Available Proteasome Inhibitor NPI-0052 Induces Killing in Multiple Myeloma (MM) Cells Resistant to Conventional and Bortezomib Therapies.
Authors: Dharminder Chauhan, Guilan Li, Klaus Podar, Teru Hideshima, Reshma Shrigarpure, Laurence Catley, Constantine Mitsiades, Nikhil Munshi, Robert Sclossman, Rena Bahjat, Saskia Neuteboom, Paul Richardson, Michael Palladino, Kenneth C. Anderson
Journal: Blood (2004)
Final analysis of the phase II, randomized, double-blind, placebo-controlled trial of single dose velafermin (CG53135–05) for the prevention of oral mucositis
Authors: M. W. Schuster, E. Anaissie, D. Hurd, W. Bensinger, J. Mason, J. McCarty, R. Rifkin, R. Maziarz, Y. Halvorsen, V. Annino, W. Hahne
Journal: Journal of Clinical Oncology (2006)

6537 Background: Oral mucositis (OM) is a commonly occurring side effect of high-dose chemotherapy (HDCT) in patients (pts) undergoing autologous hematopoietic stem cell transplant (AHSCT). Velafermin, recombinant human fibroblast growth factor 20, is being investigated for prevention of OM. Velafermin promotes epithelial and mesenchymal cell proliferation in vitro and in vivo. Methods: A phase II trial was conducted to evaluate safety, efficacy, and pharmacokinetics (PK) of velafermin. Inclusion criteria: pts undergoing HDCT and AHSCT with or without total body irradiation (TBI) were enrolled. Velafermin at 0.03, 0.1, or 0.2 mg/kg or placebo was administered as single dose IV at 24h after stem cell infusion. Safety and PK were assessed. Pts were scored daily for presence of OM using the WHO grading scale. The primary endpoint was the incidence of Grade 3/4 OM. Results: A total of 212 pts were randomized to either placebo (n=51) or velafermin at 0.03 (n=50), 0.1 (n=56), or 0.2 (n=55) mg/kg (intent-to-treat or ITT sample). 206 pts (97%) received study drug or placebo. Pt diagnoses included multiple myeloma (57%), non-Hodgkin’s (25%), or Hodgkin’s (11%) lymphoma and 13 pts (6%) received TBI as part of the conditioning regimen. The Grade 3/4 OM incidence rates (%) in the placebo or velafermin arms (0.03, 0.1, and 0.2 mg/kg) were 37, 18, 38, and 36, respectively. The primary analysis of dose dependent reduction of severe OM was not statistically significant (p = 0.549). However, velafermin at 0.03 mg/kg did reduce the incidence of Grade 3/4 OM when compared to placebo alone (p = 0.031). Duration of Grade 3/4 OM was reduced significantly in the 0.03 mg/kg when every pt was evaluated or in the 0.1 mg/kg dose when only pts with Grade 3/4 OM were included in the analysis (p = 0.037 and 0.014, respectively). A total of 5 related SAEs (3 in 0.1 mg/kg, 1 in 0.03 mg/kg, and 1 in placebo cohort) occurred within 4hr of study drug infusion. All symptoms were transient. Conclusion: Single dose velafermin at 0.03mg/kg is may be active in reducing CT induced severe OM in AHSCT pts. Safety profile supports continuing study to define the optimal dose for prevention of severe OM. A new Phase II study will be conducted to confirm velafermin activity at 0.03mg/kg dose. [Table: see text]
Phase II study of low-dose peginterferon alfa-2b antiangiogenic therapy in patients with metastatic melanoma overexpressing basic fibroblast growth factor: An Eastern Cooperative Oncology Group study (E2602).
Authors: Ronald S. Go, Sandra J. Lee, Donghoon Shin, Steven M Callister, Dean A Jobe, Robert Martin Conry, Ahmad A. Tarhini, John M. Kirkwood
Journal: Journal of Clinical Oncology (2013)

9038 Background: FGF-2 plays an important role in the pathogenesis and progression of melanoma. In particular, FGF-2 and its receptor are expressed in melanoma cells. We investigated the use of graded dosages Peg-IFN in patients with stage IV melanoma overexpressing FGF-2. Primary objective: suppression of plasma FGF-2 to normal levels (&lt; 7.5 pg/mL). Secondary objectives: clinical efficacy of Peg-IFN and its association with angiogenic factor levels (FGF-2 and vascular endothelial growth factor /VEGF). Methods: Patients were eligible if they had stage IV melanoma from any primary site. Prior systemic therapies (&lt; 4) were allowed including IFN. Plasma FGF-2 was measured at baseline (Step 1) and patients with levels &gt; 15 pg/mL allowed to receive study treatment (Step 2). Peg-IFN was given weekly at starting dose of 0.5 mcg/kg/wk with increments every 3 weeks (maximum dose: 5 mcg/kg/wk) based on serial FGF-2 levels. Results: 207 patients entered into Step 1 and 45 (22%) overexpressed FGF-2 with a median level of 22 pg/dL (range, 15-216). 29 eligible patients enrolled into Step 2 and received treatment. The median age was 64 years and most had &gt; 2 prior therapies. FGF-2 decreased in 28 (97%) patients with suppression to normal level in 10 (35%). The median time to FGF-2 suppression was 30 days (range, 14-116). The best clinical responses were PR (7%) and stable disease (17%). The median PFS and OS were 2.0 and 9.7 months, respectively. Patients who achieved FGF-2 suppression were more likely to have a response or stable disease compared to those who did not (50% vs 11%; P=.03). Landmark analysis at 63 days showed similar OS between those who achieved FGF-2 suppression and those who did not (7.8 vs 7.7 months; P=.31). VEGF decreased in 27 patients (93%) during treatment and the levels paralleled those of FGF-2 over time. We did not find a compensatory rise in VEGF level among those with FGF-2 suppression. Conclusions: Graded dose Peg-IFN suppresses FGF-2 and has activity against metastatic refractory melanoma. Complete suppression of plasma FGF-2 was observed in 35% of the patients and correlated with clinical response but not OS. Clinical trial information: NCT00049530.
Hepatobiliary abnormalities in patients with metastatic cancer treated with lapatinib
Authors: B. Moy, E. Rappold, L. Williams, T. Kelly, L. Nicolodi, J. D. Maltzman, P. E. Goss
Journal: Journal of Clinical Oncology (2009)

1043 Background: Lapatinib (LAP), a dual tyrosine kinase inhibitor (TKI), is effective in the treatment of HER-2-positive metastatic breast cancer. Liver toxicity has been reported as a side effect of several TKIs. We analyzed the liver safety of LAP using available data from 16 metastatic cancer trials. Methods: LAP (as monotherapy or in combination) was administered to 2,968 patients (pts) in metastatic cancer trials. Liver function tests were prospectively evaluated. We defined liver toxicity events as either NCI CTCAE grade (Gr) 3 or 4 alanine and aspartate aminotransaminases (ALT/AST) or meeting Hy's Law criteria (liver injury with jaundice). Results: Overall Gr 3 and 4 ALT/AST events were seen in 45/2,968 (1.5%) and 2/2,968 (0.07%) pts, respectively. Of LAP monotherapy pts, Gr 3 and 4 ALT/AST was seen in 13/1,470 (0.9%) and 1/1,470 (0.07%), respectively. Of LAP + monoclonal antibody (mAb) pts (trastuzumab or bevacizumab), Gr 3 and 4 ALT/AST was seen in 2/199 (1.0%) and 1/199 (0.5%), respectively. Ten of 645 pts (1.6%) treated with LAP + chemotherapy (capecitabine or paclitaxel) had Gr 3 ALT/AST. Twenty of 654 pts (3%) treated with LAP + letrozole had Gr 3 ALT/AST. Among 2,968 pts, Hy's law toxicity occurred in 8 (0.3%) pts: 2/1,470 (0.14%) pts treated with LAP alone, 1/199 (0.5%) pts treated with LAP + mAb, 4/645 (0.6%) pts treated with LAP + chemotherapy, and 1/654 (0.2%) pts treated with LAP + letrozole. Alternative causes of liver toxicity such as metastatic liver disease, infectious hepatitis, and heart failure will be reported at the meeting. Conclusions: Review of data from 16 clinical trials in metastatic cancer revealed low levels of liver toxicity for LAP. Oncologists should be vigilant for this rare side effect of LAP. A proposed monitoring algorithm of symptom assessment and frequency of hepatobiliary laboratory monitoring will be shown. [Table: see text]
Cytotoxic chemotherapy (Ct) for endometrial cancer: A systematic review and meta-analysis
Authors: C. Humber, J. Tierney, M. Collingwood, P. Symonds, J. Kirwan, C. Williams, J. A. Green
Journal: Journal of Clinical Oncology (2005)

5085 Background: This systematic review assesses the benefits and adverse effects of Ct in women with advanced, recurrent or metastatic endometrial adenocarcinoma. Methods: Randomised controlled trials (RCTs) comparing Ct versus another intervention (including alternative Ct) in advanced disease were considered eligible. Bibliographic databases, trials registers and reference lists of relevant publications were searched for RCTs. Eleven eligible trials were identified which accrued 1635 patients between 1977 and 2000. The majority of these trials investigated cisplatin or anthracycline-based regimens and there were no trials comparing Ct with endocrine therapy. Two reviewers extracted data from the trial reports and authors of included studies were contacted for further information, which was supplied in two cases. Results: There was wide variation in the methodological quality of the trials, with some accruing few patients, some stopping early and most excluding patients from the analysis. RR varied from 19–39%. Only 5 studies reported progression-free (PFS) and overall survival (OS) as end points, with some early trials giving no survival data after relapse. A limited meta-analysis of 563 patients in 3 trials comparing combination Ct with single agent Ct showed no significant gain in PFS or OS (OR=0.73, 95%CI 0.36–1.48, p=0.41) compared with combination Ct. Toxicity was in general higher with the combination Ct regimens. One trial showed a 3m OS benefit from the addition of paclitaxel to another combination regimen at the expense of added toxicity. Based on the evidence reviewed, there was no evidence of benefit from cytotoxic Ct in terms of symptom control or quality of life compared with best supportive care. Conclusions: The optimum Ct regimen for advanced endometrial adenocarcinoma has still to be defined, although our review suggests there may be grounds for including paclitaxel. Future trials should measure quality of life and symptom control in addition to PFS and OS. Furthermore, future trials need to consider the relative roles of endocrine therapy and cytotoxic Ct in patients with no prior drug therapy. No significant financial relationships to disclose.
A randomized trial of capecitabine (C) given intermittently (IC) rather than continuously (CC) compared to classical CMF as first-line chemotherapy for advanced breast cancer (ABC)
Authors: M. Stockler, T. Sourjina, P. Grimison, V. Gebski, M. Byrne, V. Harvey, P. Francis, A. K. Nowak, G. Van Hazel, J. Forbes
Journal: Journal of Clinical Oncology (2007)

1031 Background: Intensive treatment is not indicated for many women having first line chemotherapy for ABC. We sought to determine for such women whether oral C was preferable to classical CMF, and whether C given continuously (CC) was preferable to the same total dose given intermittently for 14 of every 21 days (IC). Methods: 325 women were randomized between June 01 and July 05 to either IC (2,000mg/m 2 /d for 14 of every 21d), or CC (1,300mg/m 2 /d for 21 of every 21d), or CMF (cyclophosphamide 100mg/m 2 /d p.o. d1–14; methotrexate 40mg/m 2 and 5-FU 600mg/m 2 , IV d1&amp;8, every 28d). Treatment was continued until disease progression (PD), unacceptable toxicity, or intolerance. Clinical and quality of life (QOL) assessments were 3–4 wkly, and imaging was 3 monthly, both until PD. The primary endpoint was quality adjusted progression-free survival (QAPFS). Overall survival (OS), PFS, response rates (RR=CR+PR), QOL, acceptability of chemotherapy and adverse events (AE) were secondary endpoints. The analysis plan was to first compare IC v CC, and if p&gt;0.05, then to combine the two arms (C = IC + CC) for comparisons v CMF. Primary analyses were with the logrank test. Cox’s models were used to calculate hazard ratios (HR), 95% confidence intervals (CI), and to adjust for other factors. All p-values and CI are 2-sided. Results: OS was longer with C than CMF (HR .72, CI .55 to .94, p=.02, medians 22 v 18 mo). PFS was similar for C and CMF overall (HR .86, CI .67 to 1.1, p=.2, median 7 mo), and over the first 6 mo (HR 1.15, CI .81 to 1.6), but longer on C than CMF beyond 6 mo (HR .62, CI .44 to .87). Response rates were similar on C and CMF (21% v 18%, p=.8). Febrile neutropenia, infection, and sore mouth were more common on CMF; hand-foot syndrome was more common on C. Chemotherapy was continued beyond 6 mo in 40% on C but only 21% on CMF. PFS, OS, RR and AE were similar for IC and CC (p&gt;0.4). Cox’s models adjusting for baseline factors corroborated all results and conclusions. Analyses of QAPFS, QOL, and acceptability of chemotherapy will be available in June 07. Conclusion: C improved overall survival with less toxicity and greater tolerability than classical CMF. C is a good first line option when more intensive treatment is not indicated. [Table: see text]
p16/Ki-67 Dual Stain Cytology for Detection of Cervical Precancer in HPV-Positive Women
Authors: Nicolas Wentzensen, Barbara Fetterman, Philip E. Castle, Mark Schiffman, Shannon N. Wood, Eric Stiemerling, Diane Tokugawa, Clara Bodelon, Nancy Poitras, Thomas Lorey, Walter Kinney
Journal: JNCI Journal of the National Cancer Institute (2015)

Background:Human papillomavirus (HPV)–based cervical cancer screening requires triage markers to decide who should be referred to colposcopy. p16/Ki-67 dual stain cytology has been proposed as a biomarker for cervical precancers. We evaluated the dual stain in a large population of HPV-positive women.
Inhibitory Anti–Factor V Antibodies Bind to the Factor V C2 Domain and Are Associated With Hemorrhagic Manifestations
Authors: Thomas L. Ortel, Karen D. Moore, Mary Ann Quinn-Allen, Takashi Okamura, Allen J. Sinclair, John Lazarchick, Ramaswamy Govindan, Françoise Carmagnol, William H. Kane
Journal: Blood (1998)
Preliminary study of combined use of PDD and NBI for detection for flat urothelial lesion.
Authors: Yoshio Naya, Masakatsu Oishi, Takashi Ueda, Yasuyuki Naitoh, Hiroyuki Nakanishi, Fumiya Hongo, Terukazu Nakamura, Kazumi Kamoi, Koji Okihara, Tsuneharu Miki
Journal: Journal of Clinical Oncology (2015)

340 Background: This prospective preliminary study is a first report to compare photodynamic diagnosis (PDD) with narrow band imaging (NBI) in the same patients with flat suspicious lesions of carcinoma in situ (CIS) of bladder. Methods: PDD was approved by the ethics committees of our institution for 10 patients with non muscle invasive bladder cancer. Between November 2012 and April 2013, 10 patients with abnormal cytology (class III or more) but undefined papillary mucosa underwent TURBT using PDD and NBI in same time. Each patient received 1.0g ALA hydrochloride (Cosmo Bio Co., Tokyo, Japan) dissolved in 50 mL water, and was given orally 3 hours before the TURBT. The bladder was mapped first under white light (WL), then under NBI, and subsequently under blue light (BL) in odd-numbered patients. The bladder was mapped first under WL, then under BL, and subsequently under NBI in even- numbered patients. Biopsies were carried out from all suspicious areas noting if NBI, PDD or both detected lesions. Random cold cup biopsies were performed from negative lesions of PDD and NBI. Results: The sensitivity and specificity of PDD for detection CIS were 1.00 and 0.714, and those of NBI were 0.75 and 0.814, respectively. There were no cancer and dysplasia in 43 lesions both PDD and NBI negative. Of 50 lesions with negative PDD, only 2 (4%) were dysplasia and there was no cancerous lesion. Of 60 lesions with negative NBI, 3 (5%) were cancer and 6 (10%) were dysplasia. The AUC for detection CIS in PDD, in NBI and in combined use of PDD and NBI were 0.869, 0.782 and 0.964, respectively. Conclusions: When both PDD and NBI were negative, the possibility of CIS might be very low. The usefulness of the combination of PDD with NBI was suggested in this study. [Table: see text]
Phase II Trial of Paclitaxel and Cisplatin in Metastatic and Recurrent Carcinoma of the Uterine Cervix
Authors: Christos A. Papadimitriou, Kyrillos Sarris, Lia A. Moulopoulos, George Fountzilas, Athanassios Anagnostopoulos, Zannis Voulgaris, Dimitra Gika, Nikolaos Giannakoulis, Emmanuel Diakomanolis, Meletios A. Dimopoulos
Journal: Journal of Clinical Oncology (1999)

PURPOSE: Both paclitaxel and cisplatin have moderate activity in patients with metastatic or recurrent cancer of the cervix, and the combination of these two agents has shown activity and possible synergism in a variety of solid tumors. We administered this combination to patients with metastatic or recurrent cervical cancer to evaluate its activity. PATIENTS AND METHODS: Thirty-four consecutive patients were treated on an outpatient basis with paclitaxel 175 mg/m 2 administered intravenously over a 3-hour period followed by cisplatin 75 mg/m 2 administered intravenously with granulocyte colony-stimulating factor support. The chemotherapy was administered every 3 weeks for a maximum of six courses. RESULTS: Sixteen patients (47%; 95% confidence interval, 30% to 65%) achieved an objective response, including five complete responses and 11 partial responses. Responses occurred in 28% of patients with disease within the radiation field only and in 57% of patients with disease involving other sites. The median duration of response was 5.5 months, and the median times to progression and survival for all patients were 5 and 9 months, respectively. Grade 3 or 4 toxicities included anemia in 18% of patients and granulocytopenia in 15% of patients. Fifty-three percent of patients developed some degree of neurotoxicity; 21% of cases were grade 2 or worse. CONCLUSION: The combination of paclitaxel with cisplatin seems relatively well tolerated and moderately active in patients with metastatic or recurrent cervical cancer. The significant incidence of neurotoxicity is of concern, and alternative methods of administration of the two agents could be evaluated. Then, further study of this combination, alone or with the addition of other active agents, is warranted.
Abstract 229: Determination of Phase-specific Biomarkers of Viral Myocarditis Induced by Theiler’s virus Using Multivariate Analyses of Viral Genome, Troponin, Transcriptome and Echocardiography Data
Authors: Eiichiro Kawai, Seiichi Omura, Fumitaka Sato, Nicholas E Martinez, Viromi Fernando, Phoebe Rollyson, Urska Cvek, Marjan Trutschl, Ikuo Tsunoda
Journal: Circulation Research (2013)

Viral myocarditis has been proposed to be initiated by viral replication in the heart (acute phase), followed by immune-mediated damage (subacute phase), where each phase requires anti-viral and immunomodulatory treatments, respectively. There are no specific biomarkers to distinguish acute from subacute phases of myocarditis while serum troponin, echocardiography, and myocardial biopsy data have been used for diagnosis clinically. To determine the phase-specific biomarkers, we used a mouse model for myocarditis induced by Theiler’s murine encephalomyelitis virus (TMEV), which belongs to the genus Cardiovirus, the family Picornaviridae. We conducted multivariate analyses of viral genome, serum cardiac troponin I, echocardiography, histology, and transcriptome using microarray data of the heart tissue harvested on 4 (acute) and 7 (subacute) days post infection (dpi). The level of viral RNA semi-quantified by RT-PCR was 10-fold higher on 4 dpi (ΔCt = 2.5×10-2 ± 4.9×10-3) than 7 dpi (ΔCt = 2.6×10-3 ± 3.0×10-4) (P &lt; 0.05). Serum troponin was undetectable in 4 of 10 mice on 4 dpi and only in 1 of 10 mice on 7 dpi; the serum troponin levels (ng/ml) on 4 dpi (42.9 ± 15.6) were significantly lower than 7 dpi (249.9 ± 62.8) (P &lt; 0.05). The levels of viral RNA and troponin were strongly correlated on 4 dpi (r = 0.79, P &lt; 0.05), but not 7 dpi (P = 0.12), suggesting that viral replication could be a major cause of myocardial damage only on 4 dpi. We found multiple high intensity cardiac lesions using echocardiography with histological myocarditis on 7 dpi, but not 4 dpi. Transcriptome analyses of microarray data showed upregulation of genes associated with innate immune responses in samples from 4 and 7 dpi, compared with controls. Samples from 7 dpi showed upregulation of genes associated with T, B, and antigen presenting cells and downregulation of cardiac myosin-related genes (Myl4, Myl7, and Mybphl), compared with 4 dpi, suggesting that acquired immune responses contribute to cardiomyocyte damage on 7 dpi. In summary, the chronological order of emergence of biomarker candidates was 1) viral genome and innate immunity, 2) troponin, and 3) acquired immunity and echo and histological changes.