Abstract：
:Robust pharmacodynamic assay results are valuable for informing go/no-go decisions about continued development of new anti-cancer agents and for identifying combinations of targeted agents, but often pharmacodynamic results are too incomplete or variable to fulfill this role. Our experience suggests that variable reagent and specimen quality are two major contributors to this problem. Minimizing all potential sources of variability in procedures for specimen collection, processing, and assay measurements is essential for meaningful comparison of pharmacodynamic biomarkers across sample time points. This is especially true in the evaluation of pre- and post-dose tumor biopsies, which suffer from high levels of tumor insufficiency due to variations in biopsy collection techniques and significant specimen heterogeneity within and across patients. Developing methods to assess heterogeneous biopsies is necessary in order to evaluate a majority of tumor biopsies collected for pharmacodynamic biomarker studies. Improved collection devices and standardization of methods are being sought in order to improve the tumor content and quality of tumor biopsies. In terms of reagent variability, we have found that stringent initial reagent qualification and quality control of R&D-grade reagents is critical to minimize lot-to-lot variability and prevent assay failures, especially for clinical pharmacodynamic questions, which often demand assay performance that meets or exceeds clinical diagnostic assay standards. Rigorous reagent specifications and use of appropriate assay quality control methodologies help to ensure consistency between assay runs, laboratories and trials to provide much needed pharmacodynamic insights into the activity of investigational agents.
journal_name
Semin Oncoljournal_title
Seminars in oncologyauthors
Ferry-Galow KV,Makhlouf HR,Wilsker DF,Lawrence SM,Pfister TD,Marrero AM,Bigelow KM,Yutzy WH,Ji JJ,Butcher DO,Gouker BA,Kummar S,Chen AP,Kinders RJ,Parchment RE,Doroshow JHdoi
10.1053/j.seminoncol.2016.06.006subject
Has Abstractpub_date
2016-08-01 00:00:00pages
484-91issue
4eissn
0093-7754issn
1532-8708pii
S0093-7754(16)30036-7journal_volume
43pub_type
杂志文章,评审abstract：:Evidence is reviewed separating unusual variants of melanoma from the large group of superficial spreading and nodular (SSM/NOD) histogenetic types. These include (1) the relationship of moles to melanoma of the SSM/ NOD types not found in melanoma arising in lentigo maligna (LMM), desmoplastic neurotrophic melanoma (...
journal_title：Seminars in oncology
pub_type： 杂志文章
doi：
更新日期：1996-12-01 00:00:00
abstract：:The current study was conducted to determine the risk of adverse outcomes among patients with monoclonal gammopathy of undetermined significance (MGUS) of the IgM class. Two hundred thirteen patients with IgM MGUS were identified in southeastern Minnesota from 1960 to 1994. The primary end point was progression to lym...
journal_title：Seminars in oncology
pub_type： 杂志文章
doi：10.1053/sonc.2003.50062
更新日期：2003-04-01 00:00:00
abstract：:Many cytotoxic therapies are available for patients with metastatic breast cancer, but response rates are low and acquired or de novo resistance is virtually universal. Among the agents that are used in the treatment of pretreated metastatic breast cancer are vinorelbine, gemcitabine, nab-paclitaxel, pemetrexed, plati...
journal_title：Seminars in oncology
pub_type： 杂志文章,评审
doi：10.1053/j.seminoncol.2011.04.005
更新日期：2011-06-01 00:00:00
abstract：:Adrenocortical cancer (ACC) is a rare, challenging disease with a broad range of clinical presentations. Often presenting in an advanced stage with a large, locally invasive primary tumor or with Cushing's syndrome, it requires a multidisciplinary approach to treatment. We discuss controversies in the evaluation and m...
journal_title：Seminars in oncology
pub_type： 杂志文章,评审
doi：10.1053/j.seminoncol.2010.10.011
更新日期：2010-12-01 00:00:00
abstract：:Lung cancer is the number one cause of cancer-related death in both men and women in the United States. Non-small cell lung cancer accounts for approximately 85% of these cases. Despite complete resection, long-term survival for patients with operable disease remains poor. Studies exploring postoperative chemotherapy ...
journal_title：Seminars in oncology
pub_type： 杂志文章,评审
doi：10.1016/s0093-7754(01)90056-9
更新日期：2001-08-01 00:00:00
abstract：:The side effects of cisplatin (75 mg/m2) in combination with paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ) (175 mg/m2 over 3 hours) are expected to be more severe and frequent than those of carboplatin (area under the concentration-time curve of 5) in combination with the same dose of paclitaxel, but...
journal_title：Seminars in oncology
pub_type： 临床试验,杂志文章,随机对照试验
doi：
更新日期：1997-10-01 00:00:00
abstract：:The recommended weekly dose and the maximum tolerated weekly dose of docetaxel (Taxotere; Rhône-Poulenc Rorer, Antony, France) have yet to be determined. We report that a weekly dose of up to 40 mg/m2 docetaxel for 6 weeks is active in pretreated patients with metastatic breast cancer. From a preliminary study, this d...
journal_title：Seminars in oncology
pub_type： 杂志文章
doi：
更新日期：1998-10-01 00:00:00
abstract：:Oxaliplatin, which was recently approved by the US Food and Drug Administration for the treatment of advanced colorectal cancer, is often administered to patients with altered liver function caused by hepatic metastases. Because of the absence of data on the clearance of oxaliplatin in patients with liver dysfunction,...
journal_title：Seminars in oncology
pub_type： 临床试验,杂志文章,多中心研究
doi：10.1016/s0093-7754(03)00400-7
更新日期：2003-08-01 00:00:00
abstract：:Cancer vaccines offer a low-toxicity approach to induce anticancer immune responses. They have shown promise for clinical benefit with one cancer vaccine approved in the United States for advanced prostate cancer. As other immune therapies are now clearly effective for treatment of advanced cancers of many histologies...
journal_title：Seminars in oncology
pub_type： 杂志文章,评审
doi：10.1053/j.seminoncol.2015.05.006
更新日期：2015-08-01 00:00:00
abstract：:Adjuvant chemotherapy in breast cancer has clearly been shown to reduce mortality. The benefits extend to pre- and postmenopausal women and those with node-negative, node-positive, estrogen receptor (ER)-positive, and ER-negative disease. Updated data regarding chemoendocrine therapy in postmenopausal women and anthra...
journal_title：Seminars in oncology
pub_type： 杂志文章,评审
doi：10.1016/s0093-7754(01)90130-7
更新日期：2001-08-01 00:00:00
abstract：:Clinical research in the treatment of epithelial ovarian cancer has entered a new phase. A pivotal Gynecologic Oncology Group study demonstrated that paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ) plus cisplatin was superior to the previous standard therapy of cyclophosphamide plus cisplatin. Confirma...
journal_title：Seminars in oncology
pub_type： 杂志文章,评审
doi：
更新日期：1997-10-01 00:00:00
abstract：:Many novel antifolate compounds with unique pharmacologic properties are currently in clinical development. These newer antifolates differ from methotrexate, the most widely used and studied drug in this class, in terms of their lipid solubility and cellular transport affinity, their level of polyglutamation, and thei...
journal_title：Seminars in oncology
pub_type： 杂志文章,评审
doi：
更新日期：1997-10-01 00:00:00
abstract：:Session V of the Colloquium was chaired by Professors Teresa López-Fernández of Spain and Grzegorz Opolski of Poland. The 3 speakers addressed cardio-oncology issues as they relate to both clinical studies and real life situations. Professor Susan Dent discussed cardio-oncology networks for patients, emphasizing the i...
journal_title：Seminars in oncology
pub_type：
doi：10.1053/j.seminoncol.2019.01.004
更新日期：2019-12-01 00:00:00
abstract：:Recent advances in the biology of multiple myeloma cell growth and survival have suggested new avenues for treatment and potential cure of this disease. Adhesion molecules on the myeloma cell surface mediate their localization in the bone marrow via binding to extracellular matrix proteins and stromal cells. Stromal c...
journal_title：Seminars in oncology
pub_type： 杂志文章,评审
doi：
更新日期：1999-10-01 00:00:00
abstract：:Ten years of interferon (IFN) therapy have followed the approval of this agent by the US Food and Drug Administration on June 5, 1986. As the first biotherapeutic approved, IFN-alpha paved the way for the many new biotherapeutics. Regardless of this long history, however, we have just touched the surface of understand...
journal_title：Seminars in oncology
pub_type： 杂志文章,评审
doi：
更新日期：1997-06-01 00:00:00
abstract：:Sentinel nodes (SNs) are the first set of nodes to receive drainage and cancer cells from a primary tumor. While there may be a single SN, frequently there are one to three or more SNs. The development of sentinel node surgery over the last decade has led to dramatic changes in the surgical approach to regional nodes ...
journal_title：Seminars in oncology
pub_type： 杂志文章,评审
doi：10.1053/sonc.2002.32894
更新日期：2002-06-01 00:00:00
abstract：:Blast crisis terminates the life of the majority (approximately 80%) of patients with CML. The time of its onset appears to be a random phenomenon, varying from a probable coincidence occurrence with the onset of CML to more than a decade after onset of the chronic phase. In most patients the diagnosis is obvious as v...
journal_title：Seminars in oncology
pub_type： 杂志文章
doi：
更新日期：1976-09-01 00:00:00
abstract：:Recent changes to the staging of melanoma, coupled with advances in surgical and medical treatment, have resulted in new methods for diagnostic evaluation and reporting of melanocytic lesions by pathologists. This review provides an update on recent changes in evaluation and reporting of primary melanoma, evaluation o...
journal_title：Seminars in oncology
pub_type： 杂志文章,评审
doi：10.1053/j.seminoncol.2012.01.005
更新日期：2012-04-01 00:00:00
abstract：:The targeting of molecular abnormalities in neoplasms may provide an opportunity to improve the selectivity of cancer therapy. Ras mutations are a common genetic event in human cancers. Other genetic changes in tumors can signal through ras-dependent pathways as well. The targeting of ras through the inhibition of Ras...
journal_title：Seminars in oncology
pub_type： 杂志文章,评审
doi：10.1016/s0093-7754(01)90286-6
更新日期：2001-10-01 00:00:00
abstract：:Knowledge of the pharmacokinetics of a drug is essential to the optimal design of the dose and schedule of chemotherapy protocols. As an extension, an understanding of the mechanism of drug action is necessary to construct the optimal strategy for combination chemotherapy. Nucleoside antimetabolites such as fludarabin...
journal_title：Seminars in oncology
pub_type： 杂志文章,评审
doi：
更新日期：1993-10-01 00:00:00
abstract：:Developments in the treatment of extensive small cell lung cancer have proven effective in palliative management but have not yielded improvements in the cure rate for this disease. Strategies involving dose escalation of chemotherapy, including de novo and late intensification dose escalation and dose escalation with...
journal_title：Seminars in oncology
pub_type： 杂志文章,评审
doi：
更新日期：1992-12-01 00:00:00
abstract：:The clinical development of the recombinant alpha interferons has provided a prototype for the clinical development of biological compounds. With over 5,000 patients now treated with these compounds, some general principles have emerged that have wider implications for phase I-II strategies for testing other biologica...
journal_title：Seminars in oncology
pub_type： 临床试验,杂志文章,评审
doi：
更新日期：1987-06-01 00:00:00
abstract：:A new era involving the evaluation of recombinant vaccines for colon cancer has begun with the concurrent emergence of insights and technologies in the fields of molecular biology and immunology. These advances include (I) the identification and cloning of an array of genes associated with the neoplastic process, such...
journal_title：Seminars in oncology
pub_type： 杂志文章,评审
doi：
更新日期：1999-12-01 00:00:00
abstract：:The curative management of gastric adenocarcinoma depends on complete resection of the primary tumor. In patients with lymph node metastases in the resected specimen, the relapse and death rates from recurrent cancer are 70% to 80%. There is continued debate over whether more extensive lymph node dissection (D2) impro...
journal_title：Seminars in oncology
pub_type： 杂志文章,评审
doi：10.1016/s0093-7754(03)00298-7
更新日期：2003-08-01 00:00:00
abstract：:Etoposide has proven to be an active agent in the treatment of a variety of neoplasms, particularly germ cell cancers and small cell lung cancer. Yet despite its widespread use, the optimal dose and schedule for etoposide remain unknown. The fact that its efficacy appears to be schedule dependent, along with the recen...
journal_title：Seminars in oncology
pub_type： 杂志文章,评审
doi：
更新日期：1992-12-01 00:00:00
abstract：:Malignant biliary obstruction, duodenal, and gastric outlet obstruction, and tumor-related pain are the complications of unresectable pancreatic adenocarcinoma that most frequently require palliative intervention. Surgery involving biliary bypass with or without gastrojejunostomy was once the mainstay of treatment in ...
journal_title：Seminars in oncology
pub_type： 杂志文章,评审
doi：10.1053/j.seminoncol.2014.12.014
更新日期：2015-02-01 00:00:00
abstract：:Although originally developed as an antitumor agent in the 1970s, dexrazoxane (DEX) is currently used as a cardioprotective agent in combination with doxorubicin (DOX). Due to concerns about anthracycline-induced cardiotoxicity at higher cumulative doses, many investigators have chosen to administer DOX by prolonged i...
journal_title：Seminars in oncology
pub_type： 临床试验,杂志文章
doi：
更新日期：1998-08-01 00:00:00
abstract：:Single-agent docetaxel has been shown to produce a significant decrease in prostate-specific antigen (PSA) levels among patients with hormone-refractory prostate cancer (HRPC). A recent study also showed that exisulind, a sulfone metabolite of the nonsteroidal anti-inflammatory drug sulindac, lengthens the median PSA ...
journal_title：Seminars in oncology
pub_type： 临床试验,杂志文章
doi：10.1016/s0093-7754(01)90156-3
更新日期：2001-08-01 00:00:00
abstract：:Several new antimetabolites have been evaluated in clinical trials in recent years. Those with the most promising activity include the structurally related purine analogs fludarabine, 2-chlorodeoxyadenosine, and 2'-deoxycoformycin. These compounds have shown impressive activity against a broad spectrum of indolent lym...
journal_title：Seminars in oncology
pub_type： 杂志文章,评审
doi：
更新日期：1992-12-01 00:00:00
abstract：:In geographic areas where there is a high risk of esophageal cancer, analysis of cells obtained from the esophagus has been used effectively to detect early lesions. This has been demonstrated on a large scale in studies from China. Using abrasive balloon cytology techniques, 75% of the cancers detected were early les...
journal_title：Seminars in oncology
pub_type： 杂志文章
doi：
更新日期：1984-06-01 00:00:00
