Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0016632 (Fox)
 1,461 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The inherent or acquired (induced) resistance of certain tumours to cytotoxic drug therapy is a major clinical problem. There are many categories of cytotoxic agent: the antimetabolites, e.g. methotrexate (MTX), N-phosphonacetyl-L-aspartate (PALA), 5-fluorouracil (5-FU), 6-mercaptopurine (6-TG), hydroxyurea (HU) and 1-beta-D-arabinofuranosylcytosine (AraC); the alkylating agents, e.g. the nitrogen mustards and nitrosoureas; the antibiotics, e.g. doxorubicin and mitomycin C; the plant alkaloids, e.g. vincristine and vinblastine; and miscellaneous compounds, such as cisplatin. There are also many mechanisms of drug resistance elucidated principally from in vitro studies. These include mutation of target genes, amplification of target and mutated genes, differences in repair capacity, altered drug transport and differences in nucleoside and nucleobase salvage pathways (Fox et al, 1991). The aim of the present review is to evaluate in detail the mechanisms of response of both normal and tumour cells to three chemotherapeutic antimetabolites, MTX, PALA and 5-FU, which are routinely used in the clinic either alone or in combination to treat some of the commonest solid tumours, e.g. breast, colon, gastric and head and neck. The normal and tumour cell response to these agents will be discussed in relation to the operation of the known alternative 'salvage pathways' of DNA synthesis and current theories of DNA damage response.
Br J Cancer 1997
PMID:Resistance to chemotherapeutic antimetabolites: a function of salvage pathway involvement and cellular response to DNA damage. 908 27

There is a need for additional data in the literature regarding elective nodal irradiation in the treatment of T2N0 squamous cell carcinoma of the glottic larynx. We examined the experience at the Fox Chase Cancer Center and performed a literature review in order to define a treatment policy. Sixteen patients with T2 squamous cell carcinoma of the glottic larynx were treated with radiation therapy. Ten patients were irradiated to the larynx alone and six to the larynx and regional nodes. None of the patients in our series experienced a nodal recurrence regardless of whether the neck was electively irradiated. A literature review of 413 patients revealed that 2.6% of patients who did not have their nodes electively irradiated and had their primary tumor controlled experienced a nodal failure compared to 3.7% if the primary and regional nodes were irradiated (P = 0.88). Similarly, there was no significant difference in the rate of nodal failure for patients who experienced a recurrence at the primary site regardless of whether they received elective nodal irradiation (P = 0.36). We recommend treatment to the larynx alone since our policy is to treat the regional nodes only when the incidence of occult lymphadenopathy in the neck exceeds 15%.
 ...
PMID:Neck failure in T2N0 squamous cell carcinoma of the true vocal cords: the Fox Chase experience and review of the literature. 912 90

We previously reported a 62% response rate and 54% 1-year survival rate for paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ) administered by 24-hour infusion in combination with fixed-dose carboplatin to treat patients with advanced non-small cell lung cancer (NSCLC). Myelosuppression proved dose limiting, but was substantially reduced by the routine use of granulocyte colony-stimulating factor during the second and subsequent cycles. Activity for paclitaxel 135 mg/m2 and 200 mg/m2 by 1-hour infusion every 3 weeks in patients with NSCLC, with minimal myelosuppression and the suggestion of a dose-response relationship, has been reported. In November 1994, we initiated a phase II trial in patients with advanced, measurable, chemotherapy-naive NSCLC using paclitaxel 175 mg/m2 given in 1 hour, and carboplatin dosed to a fixed target area under the concentration-time curve of 7.5 every 3 weeks. In the absence of grade 4 myelosuppression, paclitaxel was escalated on an intrapatient basis by 35 mg/m2 per cycle to a maximum dose of 280 mg/m2 by cycle 4. Granulocyte colony-stimulating factor was not routinely used. Of the 57 patients accrued, 44 (81%) are Eastern Cooperative Oncology Group performance status 1. The median patient age is 64 years. To date, 54 patients are fully evaluable for toxicity. In the first 20 evaluable patients accrued (cohort A), myelosuppression was tolerable, but cumulative peripheral sensory neuropathy proved dose limiting: grade > or = 1 in 15 (75%) patients and grade 3 in six (30%), generally occurring at paclitaxel doses > or = 215 mg/m2 and obligating at least three patients to be removed from study despite absence of disease progression. The protocol was consequently revised. The starting dose of paclitaxel was reduced to 135 mg/m2 with intrapatient dose escalations of 40 mg/m2 per cycle, to a maximum paclitaxel dose of 215 mg/m2, recapitulating the original dosing schema used in Fox Chase Cancer Center study 93-024. For the 35 patients enrolled in the second cohort (cohort B), treatment has been better tolerated. Of 21 evaluable patients, 13 (62%) have experienced peripheral sensory neuropathy, grade 3 in only one (5%) patient. Myelosuppression also has been less pronounced, with 44% grade 4 granulocytopenia and 38% grade > or =3 thrombocytopenia in cohort B compared with 70% and 50%, respectively, in cohort A. Of the first 22 patients accrued to cohort A, 12 (55%) had major objective responses. Median event-free survival is 24 weeks and median survival is 47 weeks. Of the 35 evaluable patients in cohort B, nine (26%) have had major objective responses. Median event-free survival is 22 weeks. It is too early to report median survival. Paclitaxel given by 1-hour infusion in combination with carboplatin at a fixed target area under the concentration-time curve of 7.5, although active in advanced NSCLC, is associated with problems that compromise its efficacy. Higher dose levels yield intolerable toxicity, evidenced by the incidence of neurotoxicity (rather than myelosuppression) that was dose and protocol limiting at paclitaxel doses exceeding 215 mg/m2. Lower doses, while more tolerable, appear to be associated with lower response rates.
 ...
PMID:Paclitaxel (1-hour) and carboplatin (area under the concentration-time curve 7.5) in advanced non-small cell lung cancer: a phase II study of the Fox Chase Cancer Center and its network. 933 Nov 28

Severe hypersensitivity reactions to paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ) were reported during early phase I trials. A premedication regimen consisting of oral steroids 12 and 6 hours before treatment with paclitaxel as well as immediate infusion of diphenhydramine and cimetidine (or ranitidine) before paclitaxel markedly decreased the incidence of hypersensitivity reactions. Subsequently, investigators at the Fox Chase Cancer Center used intravenous dexamethasone, diphenhydramine, and cimetidine immediately before paclitaxel in an effort to obviate the inconvenience of oral steroid administration. Two prospective clinical trials that use carboplatin and paclitaxel were performed in patients with ovarian cancer and in patients with non-small cell lung cancer. In both these trials, all premedication for hypersensitivity reactions was administered intravenously immediately before paclitaxel. No significant hypersensitivity reactions were reported in these two trials, and, subsequently, a large retrospective search of a computerized pharmacy database concluded that a single-dose regimen of intravenous dexamethasone, diphenhydramine, and cimetidine is a safe and convenient alternative for prevention of hypersensitivity reactions associated with outpatient paclitaxel administration.
 ...
PMID:Intravenous prophylaxis for paclitaxel-related hypersensitivity reactions. 942 58

Gemcitabine has demonstrated single-agent activity in advanced, incurable non-small cell lung cancer, yielding response rates of > or =20%, and, in combination with cisplatin, response rates of 30% to 60%. Carboplatin causes much less nonhematologic toxicity than cisplatin, and initial therapy with carboplatin yields equivalent survival in advanced non-small cell lung cancer compared with cisplatin combinations and other cisplatin analogs, despite a lower response rate. Carmichael and colleagues have identified a maximum tolerated dose of carboplatin of area under the curve 5.2 mg/mL/min administered monthly in combination with gemcitabine 1,000 mg/m2 on days 1, 8, and 15. This combination produced a response rate of 31% and a median survival of 45 weeks in 13 evaluable patients. A subsequent phase I evaluation reversing the carboplatin and gemcitabine sequence (gemcitabine --> carboplatin day 1) demonstrated no difference in toxicities, pharmacodynamics, or maximum tolerated dose. At Fox Chase Cancer Center and elsewhere, similar phase I trials will determine the maximum tolerated doses of each agent in combination using a compressed schedule with carboplatin administered every 3 weeks and gemcitabine given on days 1 and 8 only.
 ...
PMID:Gemcitabine and carboplatin in combination: phase I and phase II studies. 972 85

The data monitoring regulatory procedures, and administrative tasks associated with protocol management have become increasingly complex. Relational database technology and Internet-based connectivity offer resources to improve the quality and efficiency of protocol operations. At Fox Chase Cancer Center, we have developed a suite of database applications for protocol management and tracking of patient accrual. All data transactions and reporting occur through a graphical web browser interface using standard Internet technology. Security and confidentiality have been addressed through encryption, user authentication, address restriction, and database authority. Database management has been tightly integrated with protocol operations to avoid duplication of resources and effort. Data query functions also extend to other institutional resources, such as tumor registry and the hospital clinical laboratory, to further reduce the need for redundant data storage. Newer components, such as chemotherapy orders and toxicity reporting, have been incorporated in a modular fashion. Although custom software development can be expensive and time-consuming, it offers the best opportunity for successful integration with existing resources, staff, and procedures, as well as collaboration with other institutions.
 ...
PMID:Web-based resources for clinical protocol management. 1002 16

CD-ROM database products are in widespread use and offer potential cost savings over online products. Many libraries would find a cost-benefit analysis useful. Libraries often do not have sufficient funding simply to underwrite all costs related to CD-ROM workstations. Inexpensive menuing software permits usage tracking for data analysis and cost recovery of CD-ROM subscription, start-up, and operating costs. This article will explore the approach taken at the Fox Chase Cancer Center in Philadelphia to recover CD-ROM related expenses through user fees.
 ...
PMID:Cost recovery and usage tracking of CD-ROM databases with menuing software. 1011 82

Prostate cancer is the most common form of cancer (except skin cancer) in men. Several factors have been associated with an increased risk for prostate cancer, including age, ethnicity, family history, lifestyle, and environmental exposures. Recognition of the importance of the interaction of these factors in prostate cancer has led to an interest in their evaluation as a model both for studying genetic susceptibility patterns and for studying and providing educational tools and preventive interventions. One such model has been developed at Fox Chase Cancer Center. Critical to the implementation of the model has been the establishment of the Prostate Cancer Risk Registry (PCRR) and Prostate Cancer Risk Assessment Program (PRAP). Together, they serve as a unique resource for investigating the interaction between environmental factors and genetic susceptibility patterns; exploring the early, premalignant biological markers of prostate cancer; and prospectively assessing the quality of life (QOL) of men at risk. In addition, PRAP facilitates the evaluation of models for prostate cancer risk counseling and screening in the community. This paper describes this model for early detection and risk reduction, along with preliminary data from its first two study aims. The program is particularly relevant in view of the wealth of genetic information emerging from the Human Genome Project.
 ...
PMID:Prostate cancer risk assessment program. A model for the early detection of prostate cancer. 1020 54

Evidence suggests that locally advanced non-small cell lung cancer may be more effectively treated with induction chemotherapy followed by radiation or concurrent chemoradiation compared with radiation alone. The majority of combined modality regimens evaluated in mature clinical trials incorporated cisplatin-based combinations, but none has incorporated newer active systemic agents or fully examined the potential role of induction chemotherapy followed by concurrent chemoradiation. The Fox Chase Cancer Center and its affiliate network have evaluated induction chemotherapy with paclitaxel plus carboplatin with or without granulocyte colony-stimulating factor priming followed by concurrent systemic chemotherapy and radiation therapy in patients with locally advanced non-small cell lung cancer. The regimen has been well-tolerated and paclitaxel dose escalation continues. The major response to combined therapy was 55% in the first 38 evaluable patients, and the 1-year survival rate is 72%. Median survival is 15 months. The primary toxicity following induction therapy has been myelotoxicity, which has been mild in severity. During concurrent therapy, the major toxicity has been esophagitis; only limited nonhematologic toxicity has been observed. Other studies evaluating different chemoradiation regimens have reported varying results. Paclitaxel/carboplatin-based combinations, administered cyclically at or near full systemic dose in combination with radiation, are feasible. Randomized studies are needed to determine the proper sequencing, potential survival benefits, and relative safety profiles of these combined modality regimens.
 ...
PMID:Concurrent chemoradiation using paclitaxel and carboplatin in locally advanced non-small cell lung cancer. 1021 May 49

Fox Chase Cancer Center has adopted the "cluster concept" of networking to avoid redundancy and loss of computing time. In this manner, transfer of clinical and research data is easily accomplished.
 ...
PMID:Effective computing with clusters. 1028 40


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>