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prostate cancer

Pretreatment Tumor Hypoxia Predicts Biochemical Failure after Radiotherapy for Prostate Cancer

Hypoxia often occurs early in solid tumor development as a result of imbalances between oxygen supply and consumption and may lead to genetic and molecular signaling that influences the biology and clinical behavior of tumors and response to treatment. Milosevic and colleagues from Princess...

What You Need to Know About Glucarpidase Injection for Toxic Methotrexate Levels in Renal Impairment

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 January 2012, glucarpidase injection (Voraxaze) was...

lymphoma

Newest Indication for Rituximab as Maintenance Treatment in Non‑Hodgkin Lymphoma

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 The CD20-directed monoclonal antibody rituximab...

Everolimus: New Indication in Renal Angiomyolipoma Associated with Tuberous Sclerosis Complex

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 April 2012, the kinase inhibitor everolimus...

lymphoma

Multicenter Phase II Trial Supporting Approval of Brentuximab Vedotin in Anaplastic Large-cell Lymphoma

Systemic anaplastic large-cell lymphoma (ALCL) is an aggressive T-cell lymphoma subtype characterized by uniform expression of CD30. Apart from low- to intermediate-risk patients with ALK-positive disease, patients with ALCL have a poor prognosis when treated with conventional, anthracycline-based...

prostate cancer

Pretreatment Tumor Hypoxia Predicts Biochemical Failure after Radiotherapy for Prostate Cancer

Hypoxia often occurs early in solid tumor development as a result of imbalances between oxygen supply and consumption and may lead to genetic and molecular signaling that influences the biology and clinical behavior of tumors and response to treatment. Milosevic and colleagues from Princess...

sarcoma

Pazopanib: New Drug for Advanced Soft-tissue Sarcoma

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 April 2012, pazopanib (Votrient) was approved for the ...

solid tumors

Identification of Novel Mechanism for Suppression of Antitumor Immunity

The efficacy of cancer immunotherapy has been limited, likely reflecting in large part the incomplete understanding of the complex interactions between tumors and the immune microenvironment. A study presented at the 2012 ASCO Annual Meeting helps clarify some of these interactions. Changes in...

supportive care
pain management
palliative care

Early Access to Palliative/Supportive Care vs Usual Care Improves Pain Management

Many cancer patients remain undertreated for pain despite availability of guidelines and educational efforts to improve pain treatment. In a recent Annals of Oncology article, Bandieri and colleagues from the Italian Epidemiologia Clinico-Assistenziale del Dolore in Ospedale (ECAD-O) group report a ...

solid tumors

p53 Mutation in Advanced Solid Tumors Linked to Aggressive Course

Mutations in the tumor-suppressor protein p53, among the most common mutations in cancers, affect apoptosis, genomic stability, and angiogenesis. To determine the effect of p53 mutation on clinical characteristics and disease and treatment outcomes, Rabih Said, MD, MPH, and colleagues from The...

breast cancer

NK Cell Signature Associated with Favorable Prognosis in Breast Cancer

Tumor cell recognition by natural killer (NK) cells is mediated by the interaction of activating and inhibitory NK cell receptors with ligands expressed on the tumor cells. NK cells also express adhesion molecules that facilitate formation of the immune synapse with tumor targets. Maria Libera...

solid tumors
colorectal cancer

Single Nucleotide Polymorphisms Predict Severe Toxicity of Adjuvant Therapy in Colorectal Cancer

Oxaliplatin/fluoropyrimidine–based adjuvant therapy is of benefit in patients with resected stage II/III colon cancer, but the ability to predict risk of toxicity could improve care by permitting individualization of treatment. Ana Custodio, MD, and colleagues from GEMCAD (Grupo Español...

solid tumors

Two Single Nucleotide Polymorphisms Associated with Risk for Paclitaxel-related Peripheral Neuropathy

Peripheral neuropathy is the most common severe toxicity in patients receiving paclitaxel, and mutations in genes affecting drug metabolism, distribution, and elimination are likely to modulate risk for such neurotoxicity. In a recent study, Daniel Hertz, PharmD, and colleagues from the University...

solid tumors

Alterations in PTEN Insufficient to Predict Sensitivity to Drugs Targeting PI3K/mTOR Pathway

PTEN acts as a tumor-suppressor gene through the action of its phosphatase protein product, which participates in regulation of the cell cycle to prevent too-rapid cell growth and division. Loss of PTEN function has been shown to increase PI3K/mTOR signaling, and preclinical data suggest that PTEN...

SIDEBAR: Key Findings

When asked to comment on implications of this study, lead author Frank A. Greco, MD, remarked, “The use of this gene-expression profile assay (CancerTYPE ID, bioTheranostics, Inc) on the biopsy material of patients with carcinoma of unknown primary provides a single tissue of origin diagnosis in...

issues in oncology

Gene Profiling–guided Therapy May Improve Survival in Patients with Carcinoma of Unknown Primary

Molecular gene-expression profiling is an emerging technique to determine tissue of origin in patients with carcinoma of unknown primary, although the value of predictions from such profiling in improving treatment outcomes is unclear. In a prospective trial using tumor profiling results to direct...

leukemia

Prognostic Value of Integrated Cytogenetic and Mutational Risk Classification in Acute Myeloid Leukemia

Jay P. Patel, BS, and colleagues from Memorial Sloan-Kettering Cancer Center in New York recently performed mutational analysis of 18 genes in a subgroup of newly diagnosed acute myeloid leukemia (AML) patients who had been randomized to receive cytarabine plus high-dose or standard-dose...

colorectal cancer

Increased Adjuvant Therapy Use and Improved Survival in Dutch Elderly Patients with Stage III Colon Cancer: A Direct Correlation?

A survival benefit of adjuvant chemotherapy has been reported for select elderly patients with stage III colon cancer, but many elderly patients are not candidates for or are not given adjuvant therapy due to comorbidities and fear of toxicity. In a recent Annals of Oncology article, van...

breast cancer

Pertuzumab: New Drug for HER2-positive Metastatic Breast 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 In June 2012, pertuzumab (Perjeta) was approved for use...

lung cancer

No Improvement in Overall Survival, Worse Toxicity with Motesanib Added to Chemotherapy in Non–Small Cell Lung Cancer

Two trials (E4599 and AVAiL) have suggested a benefit to adding the anti–vascular endothelial growth factor (VEGF) monoclonal antibody bevacizumab (Avastin) to chemotherapy in patients with advanced nonsquamous non–small cell lung cancer (NSCLC). Bevacizumab acts by binding directly to circulating...

solid tumors
prostate cancer

Radiotracer Targeting of Free Prostate-specific Antigen

Serum levels of prostate-specific antigen (PSA) are widely used as a biomarker for prostate cancer, although they often do not distinguish between normal tissue and cancer and do not always accurately reflect clinical outcome. In order to overcome the fact that the small proportion of...

Expert Point of View: James O. Armitage, MD

In an accompanying editorial entitled “Who Benefits From Surveillance Imaging?” James O. Armitage, MD, University of Nebraska Medical Center, Omaha, noted that data on surveillance imaging (CT or PET/CT) indicate a general absence of survival benefit in adults with lymphomas, while pointing out...

lymphoma

Study Shows Routine CT Surveillance Overused in Pediatric Hodgkin Lymphoma

The value of routine CT surveillance monitoring of pediatric patients for recurrence of Hodgkin lymphoma has been unclear. A study of CT surveillance recently reported by Stephan D. Voss, MD, PhD, and colleagues from the Children’s Oncology Group (COG) in the Journal of Clinical Oncology showed...

multiple myeloma

Carfilzomib: New Drug with Accelerated Approval for 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 In July 2012, carfilzomib (Kyprolis) was granted...

breast cancer

No Advantage to Longer Adjuvant Chemotherapy in Women with Early Breast Cancer: CALGB 40101 Trial

The ideal duration of adjuvant therapy for women with lower-risk primary breast cancer remains unknown. The National Surgical Adjuvant Breast and Bowel Project (NSABP) B-15 trial, reported more than 20 years ago, found no difference in outcomes between six cycles of cyclophosphamide, methotrexate,...

Ziv-aflibercept with FOLFIRI in Metastatic Colorectal Cancer

In August 2012, the antiangiogenic agent ziv-aflibercept (Zaltrap) was approved for use in combination with FOLFIRI (fluorouracil, leucovorin, irinotecan) for the treatment of metastatic colorectal cancer resistant to or progressing after an oxaliplatin-containing regimen.1,2 Approval was based on...

colorectal cancer

New Indication for Cetuximab plus FOLFIRI to Treat EGFR-positive, Wild-type KRAS 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 In July 2012, cetuximab (Erbitux) was approved for use...

TRIM27 as Target in Cancer Development

The tripartite motif family protein 27 (TRIM27) is a transcriptional repressor that reduces induction of cell senescence by retinoblastoma-associated protein (RB1). High levels of TRIM27 expression occur in several human cancers and have been associated with poor prognosis in breast and endometrial ...

VEGF Pathway Biomarker for Outcome with Bevacizumab

No biomarkers are available to guide patient selection for treatment with the anti-VEGF monoclonal antibody bevacizumab (Avastin). Lambrechts and colleagues from VIB and KULeuven and University Hospital Gasthuisberg, Belgium, and F. Hoffmann-La Roche in Basel, Switzerland, have identified a locus...

Evolutionary Pathways in BRCA1-associated Breast Tumors

BRCA1 germline mutations are associated with elevated risk of breast and ovarian cancers, and somatic loss of the wild-type BRCA1 allele has been thought to be a rate-limiting initiating step in tumor development. BRCA1-associated breast tumors acquire additional somatic alterations during...

Metastasis Promoted by Cleaving and Inhibiting Proapoptotic Effect of von Willebrand Factor

Mochizuki and colleagues from Keio University in Tokyo, the Chemo-Sero-Therapeutic Research Institute in Kumamoto, and RIKEN in Saitama have shown that von Willebrand factor has proapoptotic effects and that a disintegrin and metalloproteinase 28 (ADAM28) promotes metastasis by cleaving and...

Predictive Markers for Outcome with Pazopanib in Metastatic Renal Cell Cancer

Several targeted drugs are approved for treatment of metastatic renal cell cancer, but no validated biomarkers are available for prediction of clinical outcome of treatment with these agents. In a recent study, Tran and colleagues from The University of Texas MD Anderson Cancer Center in Houston,...

Anticancer Effect of Diabetes Drug Metformin

Retrospective analyses have indicated that the antidiabetic agent metformin may be associated with a quite substantial reduction in risk of cancers. There is evidence that the anticancer effects of metformin are related to inhibition of the growth of certain cancers via activation of AMP kinase...

prostate cancer
issues in oncology

No Survival Benefit of Radical Prostatectomy vs Observation for Localized Prostate Cancer Detected by PSA Testing

The relative benefits of surgery or observation in men with prostate cancer detected by prostate-specific antigen (PSA) testing have not been defined. Randomized trials comparing radical prostatectomy with observation were conducted before widespread use of PSA testing and an observational study...

prostate cancer

Enzalutamide for Metastatic Castrate-resistant Prostate 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 In August 31, enzalutamide (Xtandi) was approved for the ...

prostate cancer

Hormonal Therapy with Enzalutamide Increases Survival in Castrate-resistant Prostate Cancer after Chemotherapy

The androgen receptor–signaling inhibitor enzalutamide (Xtandi) is reported to differ from conventional antiandrogen agents in that it inhibits androgen receptor nuclear translocation, DNA binding, and coactivator recruitment, has a greater affinity for the androgen receptor, and induces tumor...

leukemia

Bosutinib in Chronic Myelogenous Leukemia Patients with Resistance or Intolerance of Prior Therapy

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 September 4, 2012, bosutinib (Bosulif) was approved...

leukemia

Kinase Inhibitors Compared in First-line Treatment of CML

Bosutinib (Bosulif) is an oral dual Src/Abl kinase inhibitor that is active against many Bcr-Abl mutations associated with imatinib (Gleevec) resistance and that has reduced activity against nonspecific molecular targets associated with toxicities reported for other second-generation kinase...

Neuropathy Not Predictive of Outcomes with Adjuvant Taxane Therapy in Breast Cancer

Neuropathy is a common and potentially disabling adverse effect of taxane therapy, particularly weekly paclitaxel. A number of recent studies have identified single nucleotide polymorphisms that appear to increase risk of grade 2 to 4 neuropathy in patients with breast cancer who receive taxanes....

skin cancer

Vismodegib: Novel Agent for Treating Advanced Basal Cell Carcinoma

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 January 2012, vismodegib (Erivedge) was approved...

issues in oncology

Genome-wide Analysis Reveals Molecular Pathway Aberrations in Uterine Serous Cancer

The molecular pathogenesis of uterine serous carcinoma, the most aggressive form of uterine cancer, remains largely undefined. Kuhn and colleagues from Johns Hopkins Medical Institutions recently identified prominent genetic alterations in uterine serous carcinoma using whole-exome sequencing....

issues in oncology

Whole-blood RNA Expression Profiles as Prognostic Models for Castration-resistant Prostate Cancer

Survival among patients with castration-resistant prostate cancer is highly variable, and there is a scarcity of prognostic markers that could be used to stratify patients in clinical trials, improve treatment, and accelerate drug development. Two recent studies reported in Lancet Oncology have...

issues in oncology

Noninvasive 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 ...

lung cancer
issues in oncology

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)...

breast cancer

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...

breast 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...

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