tbuckley/cabot-search huggingface dataset:
Clinical activity of celecoxib (CXB) in metastatic malignant melanoma (MMM)
Authors: K. S. Wilson, S. J. Allan
Journal: Journal of Clinical Oncology (2005)

7555 Background: COX-2 is demonstrable by IHC in most primary MM, and by mRNA/protein studies in MM cell lines (Denkert, Cancer Res., 2001). Effects of COX-2 therapy (Rx) in MM include decreased endothelial cell migration, dose/time dependent decreases in invasiveness and collagenase IV production, fewer lung metastases post i.v. tumor cell inj., and reduced Matrigel invasion in MM cell lines. Analyses of COX-2 expression during melanoma progression suggest that COX-2 has a functional role (Goulet et al, Cancer Biol Ther., 2003). Following the observed regression (?“spontaneous”) of lung metastases in a MMM pt who received CXB for acute gout (http://bmj.bmjjournals.com/cgi/eletters/325/7371/26644), CXB was offered to suitable pts. who had either no/minor symptoms, or had failed other Rx. CXB is presently approved by Health Canada for familial adenomatous polyposis coli. Methods: Eligibility; age >16 yrs, surgically incurable recurrent MM. Pts. with prior IFN (adjuvant), RT, chemoRx (CT), BioCT were included. Treatment; CXB 200mg daily, Rofecoxib 12.5mg daily for 1 sulfa-allergic pt., and continued until progression (PD). Results: From May 2000 to Aug 2004, 24 pts (7 F, 17 M), 22 cutaneous, 1 anal canal, 1 choroidal MM, median age 58.4 yrs (range 24 - 85), distant mets. (N = 23), unresectable regional mets. (N = 1), were treated. Median diameter of largest metastasis was 31 mm (range 0 - 110) at start of CXB (0 = non measurable pleural effusion). Median follow-up time for living pts. is 10.3 mo. (range 3.6 - 55.2). Prior therapy; RT (N = 8), DTIC (N = 4), IFN (N = 2), BioCT (N = 1), no prior Rx (N = 12), no prior systemic Rx (NPSRx, N = 16). Two pts. were CXB - intolerant and stopped within 2 wks. Tumor regressions were seen in 5 pts; 2 CR in small volume lung mets. (1 had previous Cancervax then BioCT, 1 NPSRx), mixed stable/PR in 3 NPSRx pts. (1 bulky metastatic choroidal MM, 1 multiple lung mets., 1 bilat. neck nodes) [images to be presented]. For all pts., median survival time (MST) from first incurable metastasis was 12.7 mo., and median times to PD and MST from start of CXB were 3.3 mo. and 8.1 mo. respectively. Conclusion: CXB has clinical activity and merits further evaluation with parallel study of COX-2 expression in MMM to investigate its biologic basis. No significant financial relationships to disclose.
Pilot feasibility study: Eliciting provider and patient perspectives to help African American families cope with parental cancer.
Authors: Faith Young, Maureen Davey
Journal: Journal of Clinical Oncology (2014)

233 Background: 1.2 million African American (AA) parents/guardians of school age children may be diagnosed with cancer in 2014. AAs have a disproportionate burden and mortality from solid tumor cancers. However, AAs are poorly represented in distress intervention studies, and psychosocial oncology support services may not be designed for culturally diverse populations. The goal of this pilot study was to gather feasibility data from a sample of AA medical providers and from a sample of 100 cancer patients. This approach aided development of effective structures and procedures to recruit AA cancer patients/guardians raising school-age children for a culturally sensitive family intervention program. Methods: We developed a focus group guide for AA medical providers to define best practices for recruiting AA cancer patients into an intervention program. The focus group of AA providers (4 oncologists, 3 primary care, and 3 family practitioners) first reviewed the treatment manual for cultural content. We then conducted an anonymous patient needs assessment, broadly sampling cancer patients from outpatient and inpatient settings (n=100). Results: Providers and patients identified transportation support, refreshments, and onsite care for young children as important. Both groups recommended targeting AA parents/guardians within the first months of diagnosis, when coping with a cancer diagnosis is acute. Parents/guardians who had current concerns about their children more often reported an interest in family support, and patients felt that a location other than the cancer center would be most comfortable for their children. Conclusions: Effective treatments to help children and adolescents cope with the impact of parental cancer are critical, particularly those targeting low-income AA populations. The provider focus group and patient needs assessment identified recruitment barriers in anticipation of a randomized control trial designed to address family distress after parental cancer diagnosis. This approach has the potential to impact the nature of treatment support options available to a group that is overrepresented and underserved by existing interventions.
Zygomycosis in allogeneic hematopoietic stem cell transplant recipients receiving prophylactic voriconazole
Authors: M. De Magalhaes-Silverman, T. Carter, R. Gingrich
Journal: Journal of Clinical Oncology (2004)

6644 Background: Invasive fungal infections remain a major cause of morbidity and mortality in recipients of allogeneic hematopoietic stem cell transplants. Fluconazole has been highly effective in reducing the frequency of and mortality associated with Candida infections in that population. However, mortality due to mold infections remain very high. Voriconazole is a triazole with broad-spectrum antifungal acitivity which is active against several molds including Aspergillus. Methods: Records for 30 patients who underwent allogeneic hematopoietic stem cell transplantation and received prophylactic voriconazole at our institutuion were reviewed for evidence of mold infections. Voriconazole was administerd at a dose of 200 mg bid for the first three months after transplant or longer if patients were felt to be at high risk for mold infections. Voriconazole was adminstered orally unless patients had severe mucositis or diarrhea. Results: Amongst the 30 patients five cases of mold infections were identified: 1 case of Aspergillus pneumonia in a 56 year old man who had undergone a sibling matched T cell depleted bone marrow transplant for refractory CLL. This patient received voriconazole only for 3 days due to severe side effects. He was diagnosed with Aspergillus pneumonia 48 days after transplant and died inspite of therapy. Four cases of Zygomycosis were identified. The median age of these 4 patients was 47 years ( range 29–56). All cases were diagnosed at autopsy. The diagnosis of zygomycosis was made at median of 99 days ( range 25–196) after transplantation. Voriconazole had been prescribed to these 4 patients for a median of 46 days ( range 13–81). All had undergone matched unrelated transplants with T cell depletion ( in vitro Alemtuzumab in 1, in vitro OKT3 in 3). All had received high dose steroids (>2mg/Kg) and had ongoing graft versus host disease. Conclusions: Although Voriconazole has broad-spectrum anti fungal activity it is not active against Zygomycetes. Our findings suggest that the use of prophylactic voriconazole may lead to the emergency of other mold infections namely Zygomycetes. No significant financial relationships to disclose.
A randomized phase II trial of a drug eluting bead in the treatment of hepatocellular carcinoma by transcatheter arterial chemoembolization
Authors: R. Lencioni, K. Malagari, T. Vogl, F. Pilleul, A. Denys, A. Watkinson, J. Lammer
Journal: Journal of Clinical Oncology (2009)

4523 Background: Transcatheter arterial chemoembolization (TACE) has been shown to offer a survival benefit for patients with intermediate-stage hepatocellular carcinoma (HCC). A widely accepted TACE regimen includes the administration of a doxorubicin-in-oil emulsion followed by gelatine sponge particles. Recently, a drug-eluting bead (DEB) has been developed to enhance drug delivery to the tumor and reduce its systemic availability. Purpose of this randomized trial was to compare conventional TACE with DEB-TACE for the treatment of intermediate-stage HCC in patients with cirrhosis. Methods: Two hundred and twelve patients (185 males and 27 females; mean age, 67 years) with Child-Pugh A or B liver cirrhosis and large and/or multinodular, unresectable HCC were randomized to receive DEB-TACE (DC Bead; Biocompatibles, UK) uploaded with doxorubicin or conventional TACE with doxorubicin, lipiodol, and gelatin sponge particles. Randomization was stratified according to Child Pugh status (A or B), performance status (ECOG 0 or 1), bilobar disease (yes or no) and prior curative treatment (yes or no). Tumor response at 6 months was the primary study endpoint. An independent, blinded review of magnetic resonance imaging studies was conducted to assess tumor response according to amended RECIST criteria. Results: DEB-TACE with doxorubicin showed a higher rate of complete response, objective response and disease control compared with conventional TACE (27% vs 22%; 52% vs 44%; and 63% vs 52%, respectively; p&gt;0.05). Patients with Child Pugh B, ECOG 1, bilobar disease and recurrence following curative treatment showed a significant increase in objective response (p=0.038) compared to the control. There was a marked reduction in serious liver toxicity in patients treated with DEB-TACE. The rate of doxorubicin related side effects was significantly lower (p=0.0001) in the DEB-TACE group compared with the conventional TACE group. Conclusions: DEB-TACE with doxorubicin is safe and effective in the treatment of intermediate-stage HCC and may offer benefit to patients with more advanced disease. No significant financial relationships to disclose.
Clinical evaluation of a rapid and sensitive detection system for epidermal growth factor receptor (EGFR) mutations named PNA-LNA PCR clamp
Authors: K. Udagawa, Y. Nagai, T. Akaishi, H. Miyazawa, A. Yokote, M. Kanazawa, K. Hagiwara, M. Shimizu, K. Kaneko, K. Kobayashi
Journal: Journal of Clinical Oncology (2005)

3072 Background: Gefitinib, an inhibitor of the tyrosine kinase activity of EGFR,was introduced in the treatment of advanced non-small lung cancers (NSCLC). The responsiveness to gefitinib has been reported to closely link to the presence of EGFR mutations. Clinical samples contain many normal cells in addition to cancer cells. Direct DNA sequencing and single strand conformational polymorphism (SSCP) can only detect one mutant cell in at most 5 normal cell background, and are not sufficiently sensitive to apply to clinical specimens. Therefore, a method capable of detecting EGFR mutations in a large background of wild type EGFR genes could provide a superior clinical test. Methods: We have developed a rapid and sensitive detection system for EGFR mutations named PNA-LNA PCR clamp that can detect 11 different EGFR mutations (submitting). The study was designed to evaluate the sensitivity and the specificity of the PNA-LNA PCR clamp, and its utility in the clinical practice. Results: Forty four clinical samples (sputum:5, pleural effusion:10; pericardial effusion:2; bronchial fluid:2; fine needle aspiration:1; paraffin tissue:23; raw tissue:1) were obtained from 30 Japanese patients (adenocarcinoma:25 pts; other NSCLC:5) who had been previously untreated by gefitinib. PNA-LNA PCR clamp detected 17 pts (57%) of the 30 patients had EGFR mutations (3 mutations:2 pts; 2 mutations:6 pts; 1 mutation:9 pts). The PNA-LNA PCR clamp products were sequenced, which confirmed the PNA-LNA PCR clamp accurately detected the mutant sequences in every sample. Control experiments using mutant EGFR sequences as internal controls detected EGFR mutants in the presence of 100 to 1000-fold background of wild type EGFR. Conclusions: PNA-LNA PCR clamp could reliably detect EGFR mutations in the presence of 100 to 1000-fold background of wild type EGFR from the normal cells or tissue, indicating the method is useful to detect EGFR mutations in clinical specimens. We are now collecting data about response to gefitinib for the NSCLC patients with EGFR mutations detected by PNA-LNA PCR clamp. No significant financial relationships to disclose.
Oncology labels with clinical outcomes data since the final PRO guidance.
Authors: Kathleen A. Foley, Oren I Meyers
Journal: Journal of Clinical Oncology (2013)

88 Background: FDA released draft Guidance on Patient-Reported Outcomes (PROs) in 2006 and finalized it in 2009. The Guidance applies equally to clinician and observer outcomes (ClinROs, ObsROs; collectively, clinical outcome assessments - COAs), and defines regulatory expectations for COA instruments in pivotal clinical trials and the inclusion of COA data in approved labeling. The purpose of this review was to survey labels for oncologic drugs approved in the three years since the “PRO Guidance” was finalized and to characterize any COAs in these labels. Methods: CenterWatch maintains a list of FDA approved drugs following definitions established by the Tufts Center for the Study of Drug Development, including only drugs or NMEs newly approved by the FDA Center for Drug Evaluation and Research. From 2010 through 2013, 45 oncologic drugs were approved by the FDA. The labels and other information from the Drugs@FDA website were reviewed. Results: Few of the approved labels included any reference to COAs or data collected using PROs, ClinROs, or ObsROs. Several (e.g., carfilzomib) had clear statements indicating approval for the product was based on a predefined response rate rather than “improvement in survival or symptoms.” The exceptions are fentanyl tablets and spray, and abiraterone, all with PRO data on pain. The number of PROs in the labels reviewed was low, but the trend suggests that products reviewed by Divisions outside the Office of Hematology and Oncology Products were more likely to have a PRO. Abiraterone was an exception as it was reviewed by Oncology Products I and included patient reported pain. Conclusions: There are several explanations for the low rate of COAs in oncology labels, e.g., oncology trials tend to be unblinded. The FDA has stated that open label designs cannot support PRO claims. Yet there is still a heavy reliance on outcomes such as progression free and overall survival. Three labels were identified with PRO data on pain, two of which were specifically indicated for pain rather than tumor control. This review suggests there are opportunities for sponsors and the FDA to increase the degree to which the patient’s voice is heard during the regulatory decision process, particularly, in programs reviewed by the oncology divisions.
Docetaxel (T) and mitomycin C (M) as second-line treatment in advanced non-small-cell lung cancer (NSCLC). Results of a phase II study of the ONCOPAZ Cooperative Group
Authors: J. Feliú, G. Martín, Á. Rodríguez Jaraiz, M. Lomas, C. Madroñal, A. Galán, L. M. Antón, M. González Barón
Journal: Journal of Clinical Oncology (2005)

7337 Background: Single-agent T represents the standard treatment in NSCLC patients recurring after first-line chemotherapy. The aim was to evaluate whether T in combination with M would lead to an improved outcome with similar toxicity and increased efficacy compared to T monotherapy as second-line chemotherapy in NSCLC. Methods: Patients (pts), aged ≥18 years, with histopathological diagnosis of NSCLC with progression after first-line chemotherapy, measurable disease, ECOG < 2 and adequate bone marrow, renal and hepatic functions were included in this study. T was administered iv at 75 mg/m2 followed by M at 8 mg/m2 both on day 1, every 21 days. Results: A total of 49 pts: male/female, 41/8; median age 57 years (36–74), ECOG PS 0/1: 31%/69%. Tumor sites were lung (n=42) and mediastinum (n=7). Median number of metastatic sites was 1 located in nodes (39%), bone (29%) and adrenal (22%). Tumor histology included adenocarcinoma (43%), squamous cell (33%) and large cell (25%). A total of 230 cycles have been administered (median 5, range 2–6). Median relative dose intensity was 97% for T and 95% for M. Pts were evaluated for hematologic toxicity (1 was treated with G-CSF since cycle 1 and therefore has been excluded). The most common grade 3/4 toxicity per patient included neutropenia (13%), asthenia (10%), mucositis (6%), nauseas (6%), diarrhea (6%), dyspnea (6%), anorexia (4%), skin (4%), nail (4%) and fever (4%). Febrile neutropenia was observed in 4 pts (8%). On an intent-to-treat analysis, 1 pt achieved CR, 3 PR, 17 SD, 25 PD and 3 NE due to protocol deviation (n=1) and no measurable disease (n=2), resulting in an overall response rate of 9% (95% CI: 1–17). Median TTP was 3.6 months (95% CI: 2.6–4.7) and median OS was 10.4 months (95% CI: 7.8–12.9). Conclusions: Efficacy results obtained with T plus M are not as satisfactory as expected compared to T monotherapy, so further studies should be performed in order to find active combinations for advanced NSCLC treatment. No significant financial relationships to disclose.
Clinical significance of HuR expression, an mRNA-binding protein in non-small cell lung cancer (NSCLC)
Authors: F. Tanaka, E. Ogawa, H. Wada, M. Shanker, A. E. Garcia-Soto, C. D. Branch, I. Wistuba, J. A. Roth, R. Ramesh
Journal: Journal of Clinical Oncology (2006)

10098 Background: HuR is a nucleo-cytoplasmic shuttling protein that specifically binds to mRNA that has AU rich (ARE) sites at the 3’end and transports the RNA to the cytoplasm for protein translation. In addition to mRNA transportation, HuR plays a role in mRNA stabilization and protein translation. Preclinical studies have shown mRNA’s of several growth factors, cell-cycle regulators, and transcription-regulating proteins have ARE’s at the 3’end and bound by HuR. However, there has been reported no clinical data on HuR expression in NSCLC. Thus, in the present study, we assessed clinical significance of HuR expression in NSCLC. Patients and Methods: A total of 236 patients with completely resected p-stage I-IIIA, NSCLC, were reviewed, and HuR expression was evaluated immunohistochemically. Results (Table): HuR expression was seen in the nucleus and cytoplasm of tumor cells. Cytoplasmic HuR expression was positively correlated with tumor progression (p-stage, P&lt;0.01), especially nodal metastasis, microvessel density (MVD), and COX-2 expression. Enhanced nuclear HuR expression was also correlated with tumor progression and COX-2 expression, but not with MVD. Positive cytoplasmic HuR expression was a significant factor to predict a poor prognosis in all patients (5-year survival rates: 85% for HuR-negative and 43% for HuR-positive patients; P&lt;0.01) and in any p-stage/histology subset patients. Nuclear HuR expression status was also a significant prognostic factor in all patients, but not in all subsets. A multivariate analysis confirmed that cytoplasmic HuR status was an independent prognostic factor (hazard ratio [95% CI], 4.261 [2.109–8.609]; P&lt;0.001). Conclusions: Cytoplasmic HuR expression was correlated with tumor progression, and was a significant and independent prognostic factor in correlation with enhanced COX-2 expression and increased tumor angiogenesis. [Table: see text] No significant financial relationships to disclose.
Gastrointestinal hemorrhage in advanced non-small cell lung cancer (NSCLC) patients treated with erlotinib and celecoxib
Authors: M. J. Fidler, A. Argiris, J. D. Patel, D. H. Johnson, A. Sandler, V. Villaflor, J. Coon, L. Buckingham, P. Bonomi
Journal: Journal of Clinical Oncology (2006)

7172 Background: Erlotinib (E) was associated with superior survival in a phase III trial of previously treated advanced NSCLC patients (pts). Celecoxib (C) has been shown to potentiate the apoptotic and growth inhibitory effects of E in pre-clinical models. Methods: This was a phase II trial of E plus C in advanced NSCLC pts that failed one prior chemotherapy regimen. Primary endpoint: efficacy; secondary endpoint: toxicity. Pts received C (400mg b.i.d.) and E (150mg daily) until disease progression. Planned accrual: 40 pts. Results: 26 pts with stage IIIB/IV NSCLC were enrolled. Patient (pt) characteristics: male 65%; median age 66; ECOG performance status 0/1- 96%. Eighteen pts had tissue available for FISH and EGFR mutation analysis: 50% had chromosome 7 polysomy (&gt; 4 copies per cell); none had EGFR gains (&gt;2 EGFR/chromosome 7). Two pts had an EGFR gene mutation (1 exon 19, 1 exon 21). Response results: partial response- 2 pts (1 with exon 19 mutation), stable disease- 8 pts, and progressive disease- 16 pts (1 with exon 21 mutation). Median progression free survival (PFS) and overall survival (OS): 1.9 and 10.2 months, respectively. Grade 3/4 upper gastrointestinal bleeding (GIB) occurred in 4 pts prompting study closure. One pt was on therapeutic dalteparin and two pts receiving warfarin developed marked INR prolongation (INR &gt;10). The fourth pt had a history of peptic ulcer disease. Platelet counts at time of GIB: 142 - 559. Three pts had endoscopy and gastric or duodenal ulcers were found in all three cases. No pts were taking anti-acid medication at the time of GIB. No other pts were on therapeutic anticoagulation. Three pts without upper GIB were taking low-dose aspirin. Other toxicities: 85% grade 1/2 rash; 65% grade 1/2 diarrhea, 30% grade 1/2 nausea, 30% grade 1/2 fatigue (one grade 3 fatigue); one grade 3 pneumonitis, one grade 3 esophageal stricture. Conclusions: These observations suggest that C plus E may be associated with increased incidence of gastrointestinal ulceration and GIB and that the regimen should not be given to pts with a previous history of peptic ulcer disease or to pts requiring therapeutic anticoagulation. Based on response rate, PFS, and OS in this group of pts, it appears that results with E and C are similar to those reported for E alone. [Table: see text]
Clinical and pathological response to taxanes (T) and anthracycline (AC) based neoadjuvant chemotherapy (NAC) in locally advanced breast cancer (LABC): A retrospective analysis from a single institution in North India
Authors: S. Gupta, A. K. Vaid, N. Prakash, V. Talwar, D. C. Doval, P. Prakash, K. D. Patole, A. K. Dewan, H. K. Chaturvedi, K. Kumar, J. B. Sharma
Journal: Journal of Clinical Oncology (2007)

11107 Background: In India LABC remains a common presentation of breast cancer (BC). Pathological complete response (pCR) achievement is crucial for increasing survival in LABC. Taxanes and anthracyclines are amongst agents with highest activity in BC. We retrospectively evaluated clinical and pathological responses in LABC patients (pts) treated with T and AC based chemotherapy. Methods: 32 LABC pts with clinical stage IIB, IIIA, IIIB, IIIC who had received T &amp; AC based NAC between October 2002 and October 2006 were evaluated. Patients received doxorubicin 60mg/m2 (21 pts) or epirubicin 75 mg/m2 (11 pts) and docetaxel 75 mg/m2 (all pts) 3 weekly for 3–4 cycles followed by surgery. Most pts received same chemotherapy as adjuvant and also radiation therapy and hormonal treatment depending upon ER, PgR status. Results: Baseline characteristics of 32 pts: median age 50 years (range 26–65); all female; performance status 0–1; clinical stage IIB (3 pts), IIIA (9 pts), IIIB (16 pts), IIIC (4 pts); node positive (25 pts), hormone receptor positive (17 pts), unknown (1 pt); 29 pts received 3 cycles of NAC, 3 pts received 4 cycles of NAC. Growth factor was used in all patients. 31 pts underwent MRM; 5 pts had clinically complete response (16%), 22 pts had partial response (69%), 4 pts had stable disease (12%), 1 pt had progressive disease (3%); pathological complete response was seen in 4 pts (12 %). There were 2 events of febrile neutropenia; grade 3 or 4 neutropenia was seen in 26 pts (81%). There was no significant thrombocytopenia, cardiovascular event and hypersensitivity reaction. Conclusions: Our analysis indicates that T and AC based chemotherapy is well tolerated and effective in Indian pts with LABC with response rates similar to international studies. No significant financial relationships to disclose.