Abstract:
:Experimental and clinical observations of the proliferation of cancer cells and their responses to cytotoxic drugs already have had an impact on the design of anticancer therapies and it is possible that further understanding of the natural history of tumors will enable better treatments to be developed. This review addresses several approaches to improving the prognosis for patients with breast cancer in which our understanding of tumor dynamics plays an important role. Increasing dose intensity can be achieved by dose escalation (increasing the amount of drug) or increasing dose density (reducing the time between treatments). The Gompertzian model of tumor growth, which is concordant with many experimental and clinical observations, can offer an explanation why, although dose escalation improves the number of clinical responses, cure is still uncommon. In the Gompertzian model, smaller tumors grow faster, so tumor regrowth between treatment cycles is more rapid when cell kill is greatest. Reducing the time available for tumor regrowth (increasing dose density), which is now possible through the use of colony-stimulating factors to hasten hematopoietic recovery, may have a greater impact on clinical outcome than dose escalation. Sequential schedules allow optimal doses to be used in dose-dense cycles. Several cycles of the optimal dose of agent A, followed by several cycles of the optimal dose of agent B, may be more effective than the simultaneous combination of suboptimal doses of A and B. In this context, agents A and B may be single agents or established combinations. This tactic allows new agents, such as the taxoids, to be used in conjunction with established therapies, such as doxorubicin plus cyclophosphamide, at optimal doses in dose-intensive regimens. Although such regimens may maximize cytoreduction, this may not be sufficient to improve significantly the long-term outcome for patients with breast cancer. A recent trial using high-dose consolidation chemotherapy with autologous bone marrow support has thrown doubt on the assertion, implicit in Gompertzian cytodynamics, that optimal cytotoxic therapy can kill all tumor cells. The results of this trial suggest that a consistent number of tumor cells remain whether high-dose chemotherapy with autologous bone marrow support is used in patients in complete pathologic remission or in patients with overt relapse. If there is a lower limit to cytoreduction, other approaches must be developed to control or prevent the regrowth of residual tumor cells. This will require a better understanding of the molecular biology of breast cancer and the ability to predict and assess the sensitivity of individual patient's tumors to particular therapies. Factors such as HER2 overexpression are already being linked to sensitivity to particular agents and the products of oncogenes such as HER2 may be targeted by biologic therapies such as monoclonal antibodies. Furthering our understanding of the biology and behavior of tumor cells may lead to significant improvements in the long-term prognosis for patients with early and advanced breast cancer.
journal_name
Semin Oncoljournal_title
Seminars in oncologyauthors
Norton Lsubject
Has Abstractpub_date
1997-08-01 00:00:00pages
S10-3-S10-10issue
4 Suppl 10eissn
0093-7754issn
1532-8708journal_volume
24pub_type
杂志文章,评审abstract::In patients with recurrent, previously irradiated head and neck cancer, the traditional therapy of palliative single- or multi-agent chemotherapy yields a 30% to 40% response rate with median survival durations of 8 to 10 months. However, long-term survival is rarely observed. Reirradiation with or without concurrent ...
journal_title:Seminars in oncology
pub_type: 杂志文章,评审
doi:10.1053/j.seminoncol.2004.09.003
更新日期:2004-12-01 00:00:00
abstract::The effectiveness of current chemotherapeutic approaches for the treatment of solid tumors has reached a near plateau, suggesting we are nearing the limit of cytoreduction. It is hypothesized that this may be due to "subset effect," and that drugs administered according to responses predicted for particular subgroups ...
journal_title:Seminars in oncology
pub_type: 杂志文章
doi:10.1016/s0093-7754(01)90123-x
更新日期:2001-06-01 00:00:00
abstract::Transitional cell carcinoma of the urothelium is a highly chemosensitive tumor. Combination chemotherapy can provide both palliation and a modest survival advantage in patients with advanced disease. As shown in a recent phase III trial, the new gold standard should be considered gemcitabine/cisplatin, although toxici...
journal_title:Seminars in oncology
pub_type: 杂志文章,评审
doi:10.1053/sonc.2001.22537
更新日期:2001-06-01 00:00:00
abstract::Phase I trials of the intraperitoneal (IP) administration of cisplatin have demonstrated that the drug can be safely delivered by this route with a major increase in exposure (approximately tenfold to 15-fold) of the cavity to the cytotoxic agent compared with that of the systemic circulation. Phase I trials of IP cis...
journal_title:Seminars in oncology
pub_type: 杂志文章,评审
doi:
更新日期:1989-08-01 00:00:00
abstract::This paper is designed to provide an introduction to music therapy in the continuum of cancer care. The value and use of music therapy during diagnosis and treatment, palliation, hospice, actively dying, and bereavement have been well documented. The music therapy process will be identified, research will be shared, a...
journal_title:Seminars in oncology
pub_type: 杂志文章
doi:10.1053/j.seminoncol.2011.03.010
更新日期:2011-06-01 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::Imaging prostate cancer continues to represent a clinical challenge for both primary and recurrent disease. In the evaluation of the persistent/recurrent/metastatic prostate cancer, knowledge of cancer location (local v distant), size, and extent are essential in order to design a treatment, tailored to each patient's...
journal_title:Seminars in oncology
pub_type: 杂志文章,评审
doi:10.1016/s0093-7754(03)00359-2
更新日期:2003-10-01 00:00:00
abstract::The EORTC Lung Cancer Working Party investigated the effects of combination therapy with VP-16 (Ve-Pesid) and cisplatin in the treatment of non-small-cell lung cancer (NSCLC). Neither agent alone is recognized as being associated with a high rate of response in NSCLC, but the combination proved beneficial in our hands...
journal_title:Seminars in oncology
pub_type: 杂志文章
doi:
更新日期:1985-03-01 00:00:00
abstract::Chronic lymphocytic leukemia (CLL) is the most common adult leukemia but is currently incurable by conventional therapeutic interventions. Rituximab has proven efficacy and tolerability in non-Hodgkin's lymphoma, achieving response rates of 73% and 48% in previously untreated or relapsed/refractory indolent non-Hodgki...
journal_title:Seminars in oncology
pub_type: 杂志文章
doi:10.1053/sonc.2003.50033
更新日期:2003-02-01 00:00:00
abstract::Breast cancer patients undergoing therapeutic regimens of high-dose chemotherapy (HDCT) with circulating progenitor cell support often develop anemia. As a general consideration in the transplantation setting, red blood cell transfusions are normally required in patients who have passed the myeloablative phase after H...
journal_title:Seminars in oncology
pub_type: 杂志文章,评审
doi:10.1053/sonc.2002.33529
更新日期:2002-06-01 00:00:00
abstract::We report an open, three-armed, multicenter study being carried out to assess the optimum treatment for acute and delayed emesis and nausea in patients undergoing highly emetogenic chemotherapy. Eighty-seven patients were randomized to receive tropisetron (Navoban; Sandoz Pharma Ltd, Basel, Switzerland), tropisetron p...
journal_title:Seminars in oncology
pub_type: 临床试验,杂志文章,多中心研究,随机对照试验
doi:
更新日期:1994-10-01 00:00:00
abstract::Kaposi's sarcoma (KS) is the major neoplastic complication of the acquired immune deficiency syndrome (AIDS). Although most patients succumb to infectious complications of AIDS rather than as a direct consequence of the tumor, KS may, in some cases, pursue an aggressive clinical course resulting in considerable morbid...
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::Optimal management of cancer today requires a thorough and up-to-date understanding of cancer cell kinetics and biochemistry. This report reviews the history and current standards in these fields and how they affect the contemporary approach to breast cancer management. Also outlined are recommended avenues for future...
journal_title:Seminars in oncology
pub_type: 杂志文章,评审
doi:
更新日期:1999-02-01 00:00:00
abstract::The sequencing of targeted therapy is well established in metastatic renal cancer. Switching between different vascular endothelial growth factor (VEGF)-targeted therapies or VEGF-targeted therapies and mammalian target of rapamycin (mTOR) inhibitors are both of proven benefit. The optimal sequence remains unclear. Un...
journal_title:Seminars in oncology
pub_type: 杂志文章,评审
doi:10.1053/j.seminoncol.2013.05.002
更新日期:2013-08-01 00:00:00
abstract::Gene therapy has now become a standard experimental approach for treating cancers that have failed conventional therapies. As the understanding of the molecular nature of carcinogenesis develops, new approaches are being taken to directly target tumor cells, thus bypassing the difficulties of killing cells that are re...
journal_title:Seminars in oncology
pub_type: 杂志文章,评审
doi:
更新日期:1996-02-01 00:00:00
abstract::32P orthophosphate administered in a wide range of activity reduces or relieves the pain from osteoblastic metastases in approximately 80% of patients treated. The efficacy of this agent is equal to that of newer agents and of wide field radiotherapy, as documented in a literature review of 28 series reporting the use...
journal_title:Seminars in oncology
pub_type: 杂志文章,评审
doi:
更新日期:1993-06-01 00:00:00
abstract::For any tumor to become cancerous, various genetic mutations and biologic alterations must occur in the cell that in combination render it a malignant neoplasm. Small cell lung cancer (SCLC) is a neoplasm associated with several molecular and cellular abnormalities. SCLC is associated with early and frequent metastasi...
journal_title:Seminars in oncology
pub_type: 杂志文章,评审
doi:10.1053/sonc.2003.50019
更新日期:2003-02-01 00:00:00
abstract::This phase I dose-escalation study was undertaken to determine the maximum tolerated doses of paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ) and ifosfamide that could be administered without growth factors to previously untreated patients with non-small cell lung cancer. Forty patients with advanced n...
journal_title:Seminars in oncology
pub_type: 临床试验,杂志文章
doi:
更新日期:1996-12-01 00:00:00
abstract::The majority of patients with advanced prostatic cancer respond either to castration or estrogen therapy. In an attempt to identify an alternative hormonal therapy, 25 symptomatic stage D prostate cancer patients were treated with megestrol acetate as initial hormonal therapy. Thirty-three patients were evaluable for ...
journal_title:Seminars in oncology
pub_type: 杂志文章
doi:
更新日期:1985-03-01 00:00:00
abstract::Evidence published during several decades has shown that there is a group of epithelial ovarian tumors having histological and biological features between those of clearly benign and frankly malignant tumors. In 1963, FIGO accepted an intermediate group of ovarian carcinomas of low malignant potential. In 1973, WHO ad...
journal_title:Seminars in oncology
pub_type: 杂志文章,评审
doi:
更新日期:1998-06-01 00:00:00
abstract::Anemia is a multi-symptom syndrome involving both physical and emotional problems that can be evaluated for their impact on quality of life. Fatigue is the cardinal symptom of anemia, reported by three of four cancer patients using the general version of the Functional Assessment of Cancer Therapy (FACT-G) questionnai...
journal_title:Seminars in oncology
pub_type: 杂志文章
doi:
更新日期:1998-06-01 00:00:00
abstract::The application of molecular and genetic techniques to the study of body weight regulation have produced exciting new insights into the physiological systems governing energy expenditure, appetite, and metabolic signaling. A number of new peptides have been identified that play important roles in these regulatory syst...
journal_title:Seminars in oncology
pub_type: 杂志文章,评审
doi:
更新日期:1998-04-01 00:00:00
abstract::A primary goal of current clinical cancer research is the identification of prognostic tumor subtypes. It is increasingly clear that tumor growth depends on both internal tumor factors, and factors that are external to the tumor, such as microenvironment. We recently showed that parameter values alone are less importa...
journal_title:Seminars in oncology
pub_type: 杂志文章
doi:10.1053/j.seminoncol.2015.05.004
更新日期:2015-08-01 00:00:00
abstract::Over the last 60 years, success rates in treating childhood cancers have grown dramatically from 10% to greater than 85%. Negative effects of treatments, however, place survivors at risk for neurocognitive deficits that can make school challenging. Evidence shows that receiving special education services can benefit a...
journal_title:Seminars in oncology
pub_type: 杂志文章,meta分析,评审
doi:10.1053/j.seminoncol.2020.02.003
更新日期:2020-02-01 00:00:00
abstract::Inhibition of cellular DNA synthesis is the major action of gemcitabine. In cells, this drug is converted to its triphosphate (dFdCTP), which is incorporated into DNA and terminates DNA strand elongation. After incorporation of gemcitabine nucleotide into the DNA strand, one more deoxynucleotide is incorporated, and t...
journal_title:Seminars in oncology
pub_type: 杂志文章
doi:
更新日期:1995-08-01 00:00:00
abstract::This phase I trial was designed to determine the maximum tolerated dose of paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ) given as a 3-hour infusion in combination with carboplatin (400 mg/m2) as first-line chemotherapy for stage IIIC/IV ovarian adenocarcinoma. After premedication, paclitaxel was infu...
journal_title:Seminars in oncology
pub_type: 临床试验,杂志文章
doi:
更新日期:1996-10-01 00:00:00
abstract::Paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ) displays nonlinear pharmacokinetics in humans. Both peak plasma paclitaxel concentrations and areas under the curve (AUCs) of the concentration versus time profiles will change disproportionately to changes in dose. Models that accurately describe the pla...
journal_title:Seminars in oncology
pub_type: 杂志文章,评审
doi:
更新日期:1995-06-01 00:00:00
abstract::Over the past 5 years there has been a renewed interest in the use of monoclonal antibodies and immunoconjugates in the treatment of nonhematologic malignancies. This enthusiasm has stemmed from advances in recombinant technology allowing for the production of chimeric and humanized antibodies, from Food and Drug Admi...
journal_title:Seminars in oncology
pub_type: 杂志文章,评审
doi:
更新日期:2000-12-01 00:00:00
abstract::Dry mouth (xerostomia) is one of the most common complaints following radiation therapy (RT) for head and neck cancers. Notably, RT causes irreparable damage to salivary glands that increases the risk for severe and long-term oral and pharyngeal disorders. Several strategies in the treatment of head and neck cancers h...
journal_title:Seminars in oncology
pub_type: 杂志文章,评审
doi:10.1053/j.seminoncol.2004.12.009
更新日期:2004-12-01 00:00:00
abstract::The potential benefits of docetaxel (Taxotere; Aventis, Antony, France) to patients with previously-treated non-small cell lung cancer have been evaluated in two prospective randomized phase III trials. In one study, patients with stage IIIB/IV non-small cell lung cancer who had failed previous cisplatin-based chemoth...
journal_title:Seminars in oncology
pub_type: 杂志文章
doi:
更新日期:2001-02-01 00:00:00