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Showing 6051 - 6100Noninvasive Measurement of Interstitial Fluid Pressure as Marker of Tumor Aggressiveness
Increased interstitial fluid pressure in tumors can cause metastatic dissemination and treatment resistance. Study of interstitial fluid pressure has been challenging due to a lack of noninvasive imaging strategies. In a recent study, Hompland and colleagues from the Institute of Cancer Research at ...
Phase II Study Suggests Advantage of Irreversible Pan-HER Inhibition in Advanced NSCLC
Dacomitinib is a new tyrosine kinase inhibitor that forms irreversible covalent bonds with the ATP domain of each of the three kinase-active members of the HER family—EGFR/HER1, HER2, and HER4. Agents such as erlotinib (Tarceva) and gefitinib (Iressa), which are of proven benefit in advanced...
Impaired Plasmacytoid Dendritic Cell IFN-α Production May Contribute to Breast Cancer Progression
Infiltration and dysfunction of immune cells has been observed in numerous cancers. After finding that plasmacytoid dendritic cells (pDC) in primary breast tumors correlated with unfavorable prognosis, Sisirak and colleagues from INSERM (Institut National de la Santé et de la Recherche Médicale)...
Mutational Activation of PI3K-AKT Pathway and Change in HER2 Expression in Trastuzumab-resistant Breast Cancer
Insensitivity of HER2-amplified breast cancer to trastuzumab (Herceptin) has been associated with both changes in HER2 expression and activation of the PI3K-AKT pathway in laboratory studies. Chandarlapaty and colleagues from Memorial- Sloan Kettering Cancer Center in New York and Fox Chase Cancer...
HIV Protease Inhibitor Nelfinavir Selectively Inhibits HER2-positive Breast Cancer Cells
Shim and colleagues from Johns Hopkins School of Medicine in Baltimore, the National Cancer Institute in Bethesda, and Emory University School of Medicine in Atlanta have recently shown that the HIV protease inhibitor nelfinavir (Viracept) is a selective inhibitor of HER2-positive breast cancer...
Effects of LKB1 Mutation and mTOR Inhibition on IGFR1 Pathway in NSCLC
LKB1 is a serine/threonine kinase that has been found to be mutated in approximately 20% to 30% of patients with non–small cell lung cancer (NSCLC). LKB1 acts as a tumor suppressor by activating AMPK, and loss of LKB1 by point mutation or deletion suppresses AMPK, leading to increased mTOR...
PD-1 Blockade Increases Transferred T-cell Migration to Tumors
One reason that adoptive cell transfer has met with limited clinical success is that approaches based on this strategy have not fully taken into account the role of the tumor microenvironment as a limiting factor in immunotherapy. Recently reported studies by Peng and colleagues1 from The...
Ruxolitinib: Novel Drug for Myelofibrosis
In the Clinic provides overviews of novel oncology agents, addressing indications, mechanisms, administration recommendations, safety profiles, and other essential information needed for the appropriate clinical use of these drugs. Indication In November 2011, ruxolitinib (Jakafi) was approved for...
Intermittent Androgen Suppression in Prostate Cancer Noninferior to Continuous Suppression, Associated with Some QOL Benefit
A recently reported National Cancer Institute of Canada (NCIC) Clinical Trials Group study, reported by Crook and colleagues in The New England Journal of Medicine, showed that intermittent androgen suppression was associated with noninferior overall survival when compared with continuous...
Albumin-bound Paclitaxel in First-line Treatment of Advanced NSCLC
In the Clinic provides overviews of novel oncology agents, addressing indications, mechanisms, administration recommendations, safety profiles, and other essential information needed for the appropriate clinical use of these drugs. Indication On October 11, 2012, paclitaxel protein-bound particles...
Nab-paclitaxel vs Solvent-based Paclitaxel in First-line Treatment of Advanced Non–Small Cell Lung Cancer: Final Results
Nanoparticle albumin-bound (nab)-paclitaxel (Abraxane) is a solvent-free paclitaxel formulation intended to reduce solvent-related adverse reactions and improve tumor penetration via the physiologic transport properties of albumin. The final results of a phase III trial comparing nab-paclitaxel and ...
Adjuvant Chemotherapy for Breast Cancer Predicted by Disease, Age, and Insurance Type, but Not by Race
Breast cancer mortality has been found to be higher among black and Hispanic women than among white women, with the differences in outcome being attributed in part to more advanced disease stage and greater frequency of unfavorable tumor biology among black and Hispanic women. Studies to date have...
Regorafenib, Multikinase Inhibitor, for Previously Treated Metastatic Colorectal Cancer
In the Clinic provides overviews of novel oncology agents, addressing indications, mechanisms, administration recommendations, safety profiles, and other essential information needed for the appropriate clinical use of these drugs. Indication On September 27, 2012, regorafenib (Stivarga) was...
Trastuzumab Emtansine Improves Survival vs Capecitabine plus Lapatinib in Second-line HER2-positive Breast Cancer
Trastuzumab emtansine (T-DM1) is an antibody-drug conjugate composed of trastuzumab bound to the cytotoxic microtubule inhibitor emtansine (DM1, derivative of maytansine) by a stable linker. Trastuzumab targets the conjugate to HER2 receptors, and the linker releases the cytotoxic agent when the...
No Survival Benefit for Oxaliplatin Added to Adjuvant Therapy in Stage II or Elderly Patients with Colon Cancer
Oxaliplatin plus fluorouracil (5-FU)/leucovorin or capecitabine (Xeloda) is a standard of care in adjuvant therapy for stage III colorectal cancer. There is ongoing debate about whether any adjuvant therapy is of benefit in patients with stage II disease, and it is not routinely recommended in this ...
Role of Glutamate and Effect of Its Blockade in Prostate Cancer
Glutamate plays a role in oncogenic metabolic and signaling pathways. In a recently reported study, Koochekpour and colleagues from the Roswell Park Cancer Institute in Buffalo, NY, investigated potential correlations of glutamate levels with prostate cancer in patients with primary or...
Significant Reduction in Cancer Risk Seen with Daily Multivitamin Use in Middle-aged and Older Men
Large-scale trials over the past several years have shown a general lack of effect of single vitamins or small numbers of vitamins given at high doses in preventing cancer. However, as recently reported in JAMA by Gaziano and colleagues, the Physicians’ Health Study II has found a modest but...
Revised Everolimus Dosing and New Safety/Efficacy Data for Approval in Subependymal Giant Cell Astrocytoma
On August 29, 2012, everolimus in a tablet for oral suspension form (Afinitor Disperz) was given accelerated approval for the treatment of pediatric and adult patients with tuberous sclerosis complex who have subependymal giant cell astrocytoma (SEGA) that requires therapeutic intervention but...
SIDEBAR: REPORT ADVERSE EVENTS
Health-care professionals should report all serious adverse events suspected to be associated with the use of any medicine or device to FDA’s MedWatch Reporting System by completing a form online at http://www.fda.gov/medwatch/report.htm, by faxing (1-800-FDA-0178), by mailing the postage-paid...
Liposomal Vincristine for Adult Patients with Relapsed/Refractory Acute Lymphoblastic Leukemia
In the Clinic provides overviews of novel oncology agents, addressing indications, mechanisms, administration recommendations, safety profiles, and other essential information needed for the appropriate clinical use of these drugs. Indication In August 2012, vinCRIStine sulfate LIPOSOME injection...
Effects of LKB1 Mutation and mTOR Inhibition on IGFR1 Pathway in Non-small Cell Lung Cancer
LKB1 is a serine/threonine kinase that has been found to be mutated in approximately 20% to 30% of patients with non–small cell lung cancer (NSCLC). LKB1 acts as a tumor suppressor by activating AMPK, and loss of LKB1 by point mutation or deletion suppresses AMPK, leading to increased mTOR...
Statin Use Associated with Reduced Cancer-related Mortality in Danish Study
Cancer-related mortality among patients in the Danish population receiving a diagnosis of cancer at age ≥ 40 years between 1995 and 2007 was significantly reduced in those who were receiving statin therapy at the time of diagnosis, according to an analysis reported by Nielsen and colleagues in The...
Gene Profiling Directs Site-specific Therapy for Carcinoma of Unknown Primary Site
Patients with carcinoma of unknown primary site usually receive empiric therapy (eg, with taxane/platinum or gemcitabine/platinum regimens), resulting in a median overall survival of approximately 9 months. As reported recently in Journal of Clinical Oncology, Hainsworth and colleagues have shown...
Faster Rituximab Infusion for Previously Untreated Follicular Non-Hodgkin and Diffuse Large B-cell Lymphomas
On October 19, 2012, FDA approved a 90-minute infusion for rituximab (Rituxan) starting at cycle 2 for patients with previously untreated follicular non-Hodgkin or diffuse large B-cell lymphoma who do not experience a grade 3 or 4 infusion-related reaction during cycle 1.1 Patients with clinically...
Omacetaxine for Chronic or Accelerated Phase CML Patients with Resistance/Intolerance to Tyrosine Kinase Inhibitors
In the Clinic provides overviews of novel oncology agents, addressing indications, mechanisms, administration recommendations, safety profiles, and other essential information needed for the appropriate clinical use of these drugs. Indication On October 26, 2012, the FDA granted accelerated...
Tumor Grade Is Associated with Risk for Venous Thromboembolism
Recent data suggest that risk for venous thromboembolism is associated with biologic aggressiveness of cancer. Findings in the Vienna Cancer and Thrombosis Study, recently reported by Ahlbrecht and colleagues in Journal of Clinical Oncology, indicate that patients with higher-grade tumors are at...
Most Patients Do Not Report that Cure Is Highly Unlikely with Chemotherapy for Advanced Cancer
Chemotherapy for metastatic lung or colorectal cancer can provide palliation and modestly prolong life, but is not curative. In a study recently reported in The New England Journal of Medicine, Jane C. Weeks, MD, of Dana-Farber Cancer Insitute, and colleagues found that the majority of patients...
SIDEBAR: REPORT ADVERSE EVENTS
Health-care professionals should report all serious adverse events suspected to be associated with the use of any medicine or device to FDA’s MedWatch Reporting System by completing a form online at http://www.fda.gov/medwatch/report.htm, by faxing (1-800-FDA-0178), by mailing the postage-paid...
Cabozantinib in Metastatic Medullary Thyroid Cancer
In the Clinic provides overviews of novel oncology agents, addressing indications, mechanisms, administration recommendations, safety profiles, and other essential information needed for the appropriate clinical use of these drugs. Indication On November 29, 2012, cabozantinib (Cometriq) was...
Patient Expectations of Benefit in Early-phase Trials: Ethics Issues in Informed Consent
It has been found that many patients in early-phase oncology trials believe their chance of benefit to be much higher than estimates derived from historical data.1-3 In a recently reported study in Journal of Clinical Oncology, Kevin P. Weinfurt, PhD, of Duke Clinical Research Institute, and...
Ponatinib in Chronic Myeloid Leukemia and Philadelphia Chromosome–positive Acute Lymphoblastic Leukemia
In the Clinic provides overviews of novel oncology agents, addressing indications, mechanisms, administration recommendations, safety profiles, and other essential information needed for the appropriate clinical use of these drugs. Indication On December 14, 2012, ponatinib (Iclusig) was granted...
Subcutaneous Trastuzumab a Potential Alternative to Intravenous Administration in Breast Cancer
Subcutaneous administration of trastuzumab might offer improvements in patient convenience and resource use compared with conventional intravenous administration (Herceptin). A new subcutaneous trastuzumab formulation containing a fixed dose of 600 mg and recombinant human hyaluronidase PH-20...
Abiraterone in Patients with Metastatic Castration-resistant Prostate Cancer and No Prior Chemotherapy
In the Clinic provides overviews of novel oncology agents, addressing indications, mechanisms, administration recommendations, safety profiles, and other essential information needed for the appropriate clinical use of these drugs. Indication On December 10, 2012, abiraterone acetate (Zytiga)...
Abiraterone Benefits Patients with Metastatic Prostate Cancer Who Have Had No Previous Chemotherapy
The androgen biosynthesis inhibitor abiraterone acetate (Zytiga) has been shown to increase radiographic progression-free survival and delay clinical decline and initiation of chemotherapy in a clinical trial in castration-resistant patients with metastatic prostate cancer who have had no prior...
Expert Point of View: Sarah B. Goldberg, MD, MPH
In a commentary accompanying reporting of the phase II study of the MEK inhibitor selumetinib by Dr. Pasi A. Jänne, MD, PhD, and colleagues, Sarah B. Goldberg, MD, MPH, Assistant Professor of Medicine, and colleagues at Yale Cancer Center, New Haven, Connecticut, noted that KRAS, a member of the...
Selumetinib/Docetaxel Shows Promising Activity in Previously Treated KRAS-mutant Non-Small Cell Lung Cancer
Currently, there are no approved therapies for KRAS-mutant non–small cell lung cancer (NSCLC), and few clinical trials have been performed specifically in this setting. In a recent article in Lancet Oncology, Pasi A. Jänne, MD, PhD, Scientific Director, Belfer Institute for Applied Cancer Science,...
Bevacizumab plus Chemotherapy after Progression of Metastatic Colorectal Cancer on First-line Therapy Including Bevacizumab
In the Clinic provides overviews of novel oncology agents, addressing indications, mechanisms, administration recommendations, safety profiles, and other essential information needed for the appropriate clinical use of these drugs. Indication On January 23, 2013, bevacizumab (Avastin) was approved...
Use of Beta-blockers Associated with Improved Survival in Patients with NSCLC Receiving Definitive Radiation Therapy
As reported recently in Annals of Oncology, a retrospective study by Wang and colleagues showed that use of beta-adrenergic receptor antagonists (beta-blockers), typically used in treatment of hypertension and heart disease, was associated with significantly improved distant metastasis–free...
More Brief Reports from ASH, Including New Data in Leukemia, Lymphoma, and Myelodysplastic Syndrome
At the 54th Annual Meeting of the American Society of Hematology (ASH), held in Atlanta, nearly 5,000 abstracts were presented in oral sessions and posters. As part of our ongoing comprehensive coverage from the meeting, here are several more studies of note. New Targets in Acute Myeloid Leukemia...
Study Shows Little Association of Multidisciplinary Tumor Boards with Measures of Care
A survey of Veterans Affairs (VA) medical centers recently reported by Nancy L. Keating, MD, MPH, and colleagues at Harvard Medical School in the Journal of the National Cancer Institute showed that the presence of multidisciplinary tumor boards had little association with rates of recommended...
Analysis Shows No 10-year Survival Advantage in Patients with Ovarian Cancer and BRCA1 or BRCA2 Mutations
Several studies have suggested that short-term overall survival for women with ovarian cancer and BRCA1 or BRCA2 mutations is better than that in patients without such mutations. Indeed, a recent report by Kelly L. Bolton, PhD, and colleagues indicated that 5-year overall survival was 36% for...
FOXP3 Expression Linked to Better Survival with Adjuvant Anthracycline Not Followed by Taxane in Breast Cancer
The French UNICANCER-PACS 01 trial compared six cycles of anthracycline-based adjuvant therapy with FEC (epirubicin, cyclophosphamide, fluorouracil; FEC6) vs three cycles of FEC followed by three cycles of docetaxel (FEC/docetaxel) in patients with node-positive primary breast cancer. After...
Expert Point of View: Nasser H. Hanna, MD
In an accompanying editorial, Nasser H. Hanna, MD, of Indiana University, Indianapolis, suggested that although the question of two chemotherapy drugs vs one in this setting made sense at the time GOIRC 02-2006 was initiated, advances in understanding of the heterogeneity of non–small cell lung...
No Benefit of Adding Carboplatin to Pemetrexed in Second-line Treatment of Patients With Advanced Non–Small Cell Lung Cancer
An Italian randomized phase II study (GOIRC 02-2006 study) recently reported in Journal of Clinical Oncology by Andrea Ardizzoni, MD, of Azienda Ospedaliero-Universitaria in Parma, Italy, and colleagues showed no progression-free survival benefit of adding carboplatin to pemetrexed (Alimta) in...
Patients Receiving Palliative Radiation Therapy for Metastatic Non–Small Cell Lung Cancer May Be Overtreated
Many patients receiving palliative radiation therapy to the bone or chest for metastatic non–small cell lung cancer (NSCLC) may be receiving a greater number of treatments and higher doses than are supported by current evidence, according to a Cancer Care and Outcomes Research and Surveillance...
Pomalidomide in Previously Treated Multiple Myeloma
In the Clinic provides overviews of novel oncology agents, addressing indications, mechanisms, administration recommendations, safety profiles, and other essential information needed for the appropriate clinical use of these drugs. Indication On February 8, 2013, the immunomodulatory agent...
Three-marker Assay for Early Detection of Renal Cancer
Early detection of renal cell carcinoma using biomarkers remains challenging. Kim and colleagues recently evaluated a three-marker assay consisting of nicotinamide N-methyltransferase (NNMT), L-plastin (LCP1), and nonmetastatic cells 1 protein (NM23A). After validation of the three-marker assay in...
Mixed-lineage Kinase 4 Interacts with Activated RAS Signaling in Colorectal Cancer
Colorectal cancer that is microsatellite stable but chromosomally unstable is characterized by poor prognosis and remains largely intractable at the metastatic stage. Mutational analysis has shown that the mixed lineage kinase 4 (MLK4) protein kinase is frequently mutated in microsatellite-stable...
Effects of siRNA Combining TGF-β1 Silencing and RIG-I Activation in Pancreas Cancer
Dysregulation of TGF-β signaling promotes tumor growth, invasion, metastasis, and a potent immunosuppressive network in pancreas cancer. A strategy for disrupting the tumor-promoting pathway is the silencing of TGF-β by use of small-interfering (si) RNA. Ellermeier and colleagues found that the...
p53 Inactivation in the Tumor Microenvironment Promotes Tumor Progression via Immunosuppressive Lymphoid-like Stromal Network
Inactivation of the tumor suppressor p53 through somatic mutations is observed in approximately half of cancers. The finding that p53 mutations sometimes occur in tumor-associated fibroblasts and are correlated with an increased rate of metastases and poor prognosis suggests that p53 dysfunction in ...
