摘要:

Fostriecin is a novel antitumor antibiotic.In vitrostudies showed that fostriecin inhibits DNA topoisomerase II (Topo II) catalytic activity, protein phosphatases involved with cell-cycle control and histone phosphatases. The relative contribution of these mechanisms to the antitumor activity has not been elucidated, but Topo II inhibition seems to be the major mechanism of action atIn vitrocytotoxic fostriecin levels. Tumor cell lines with decreased Topo II content showed similar or increased sensitivity to fostriecin, compared to the parent cell lines. The reduced-folate carrier is probably responsible for the cellular uptake of fostriecin. The possible clinical consequences of theseIn vitroobservations are discussed.

ISSN:0959-4973    

出版商:OVID    

年代:1997

数据来源: OVID

摘要:

During the last decade, the oxazaphosphorine trofosfamide was underestimated partly due to its unsuitability for i.v. use. Oral dally doses of 150 mg were tolerated well and showed appreciable response rates in the treatment of lymphoma. Furthermore, activity in sarcoma and cancers sensitive to oxazaphosphorines in general seems probable, because ifosfamide is the main metabolite of trofosfamide. Due to its oral mode of application and good tolerance, trofosfamide will be an important option in view of the increasing demand for treatment regimens suited for an outpatient basis. Results of the majorin vitro, in vivoand clinical studies are reported for evaluation of its significance in chemotherapy today.

ISSN:0959-4973    

出版商:OVID    

年代:1997

数据来源: OVID

摘要:

A total of 34 patients with advanced ovarian cancer, who relapsed 1–72 months after at least one first-line cisplatin-based chemotherapy protocol, were treated with carboplatin, 350mg/m2q 4 weeks, with the adjunct of primary prophylactic granulocyte colony stimulating factor (G-CSF; filgrastim), 300 or 480 μg daily, days 5–9. Over 90% of the anticipated dose of carboplatin could be administered. Partial response, defined as a decline in CA-125 of 50% or more on two consecutive samples, occurred in 42%, while 15% of patients achieved a complete response (no clinical signs of disease with normalization of CA-125). Survival from start of carboplatin treatment was 23 months. Myelo-suppression was the most important toxicity with 35% of patients experiencing grade 4 thrombocytopenia of short duration. Grade 4 leucopenia occurred in only one patient. It is concluded that single-agent carboplatin, with the adjunct of prophylactic G-CSF, can be administered with adequate dose intensity, and is an effective and acceptable palliative treatment for patients with relapse after first-line cisplatin-based chemotherapy.

ISSN:0959-4973    

出版商:OVID    

年代:1997

数据来源: OVID

摘要:

Itasetron hydrochloride is a new 5-hydroxytryptamine3(5-HT3) antagonist. Experimental Investigations show that orally it is rapidly absorbed (about 90 min), is highly bioavailable (greater than 90%), has a long half-life (about 12 h) and is more potent (about 10 times) in animal models than ondansetron, currently standard therapy for the prophylactic control of chemotherapy induced nausea and vomiting. This paper describes the results of a study designed to assess the efficacy and tolerability of five (0.5, 1, 2, 4 and 8 mg) twice-daily doses of itasetron hydrochloride, in comparison with 8 mg b.i.d. ondansetron. Assessments were made in patients (n= 104) with histologically confirmed cancer (excluding head and neck tumors) and about to receive their first course of moderately emetogenic chemotherapy. Itasetron hydrochloride demonstrated comparable efficacy to ondansetron; no statistically significant between-group differences were observed in the primary (complete response rate) or secondary (nausea and delayed emesis) efficacy criteria. Adverse events were similar in type and incidence across all treatment groups, and were those expected for this therapeutic class. The tolerability of itasetron hydrochloride was assessed as ‘very good’ or ‘rather good’ by 81% of patients and 89% of physicians. In conclusion, itasetron hydrochloride is effective and well tolerated in patients receiving moderately emetogenic chemotherapy. Oral doses of 1 mg b.l.d. or above will be used in further clinical studies.

ISSN:0959-4973    

出版商:OVID    

年代:1997

数据来源: OVID

摘要:

Cladribine (2-chloro-2′-deoxyadenosine, CdA) is a purine nucleoside analog with activity against lymphoproliferative and autoimmune disorders. 2-Chloro-2′-arabino-fluoro-2′-deoxyadenoslne (CAFdA), a derivative of CdA with better acid stability, shows a similarin vitrospectrum of activity as CdA. 2-Chloroadenine (CAde) is the major catabolite of both CdA and CAFdA. We have developed a high performance liquid chromatography method to measure CdA, CAFdA and their metabolite CAde in plasma. This method employees an internal standard, chloroadenosine (CAdo), and a C8solid-phase extraction to isolate and concentrate the substances. Chromatographic separation was achieved using a C8reverse-phase column, with UV detection at 265 nm, which gives a limit of detection of 1 nmol/l for all substances. The method was reproducible with intra- and inter-assay coefficients of variations below 6% at 50 nmol/l and at 5 nmol/l below 23%. The average recoveries of CdA, CAde, CAFdA and the internal standard were higher than 70%. Stability studies of authentic patient samples show that samples containing CdA should be kept in a refrigerator or on ice to prevent degradation. Plasma containing CAde should not be kept at −20°C for longer than 10 weeks before analysis. CdA and CAFdA remain almost stable during storage at −20°C for 12 weeks.

ISSN:0959-4973    

出版商:OVID    

年代:1997

数据来源: OVID

摘要:

In this phase IB study, 24 patients with advanced colorectal cancer were treated with escalating doses of weekly chronomodulated 48 h infusions of 5-fluorouracil (5-FU) biochemically modulated by methotrexate 40 mg/m2and (6S)-leucovorin 8 × 45 mg orally. Two daily peak delivery periods (PDP), during which 65% of the daily dose was administered, were investigated: from 18.00 to 0.30 h and from 0.00 to 06.30 h. The maximal tolerated dose of 5-FU was 2800 mg/m2/48 h, with a PDP from 18.00 to 0.30 h.

ISSN:0959-4973    

出版商:OVID    

年代:1997

数据来源: OVID

摘要:

Anorexia and cachexia, major problems in patients with cancer, lead to decreased caloric intake and weight loss. Successful treatment of these conditions has a positive effect on patients' quality of life. Among the pharmacologic treatments, partial effects have been observed following administration of corticosteroids, anabolizing drugs and synthetic progestogens such as megestrol acetate and medroxyprogesterone acetate (MPA). The aim of the present study was to evaluate whether MPA is able to influence the quality of life of neoplastic patients undergoing different chemotherapeutic regimens and/or radiotherapy for different tumor types. A series of 279 cancer patients undergoing either chemotherapy and/or radiotherapy treatment for different tumor types was randomly allocated to receive either MPA or no treatment. We explored the effect of MPA oral suspension at the daily dose of 1000 mg for 12 weeks (group A) or no treatment (group B). Our data show an Increase of body weight in group A patients and improvement in performance status. The outcome of the present study strongly demonstrates that therapy with MPA plays a fundamental role in ameliorating the complex symptomatology of cancer patients in intermediate or advanced stage of the disease undergoing casual treatment with chemotherapy and/or radiotherapy.

ISSN:0959-4973    

出版商:OVID    

年代:1997

数据来源: OVID

ISSN:0959-4973    

出版商:OVID    

年代:1997

数据来源: OVID

ISSN:0959-4973    

出版商:OVID    

年代:1997

数据来源: OVID

摘要:

Pharmacologically safe compounds that can inhibit the proliferation of tumor cells have potential as anticancer agents. Curcumin, a diferuloylmethane, is a major active component of the food flavor turmeric (Curcuma longa) that exhibits anticarcinogenic propertiesin vivo. In vitro, it suppressedc-jun/Ap-1 and NF-κB activation and type 1 human immunodeficiency virus long-terminal repeat-directed gene expression. We examined the antiproliferative effects of curcumin against several breast tumor cell lines, including hormone-dependent and independent and multi-drug-resistant (MDR) lines. Cell growth inhibition was monitored by [3H]thymidine incorporation, Trypan blue exclusion, crystal violet dye uptake and flow cytometry. All the cell lines tested, including the MDR-positive ones, were highly sensitive to curcumin. The growth inhibitory effect of curcumin was time- and dose-dependent, and correlated with its inhibition of ornithine decarboxylase activity. Curcumin preferentially arrested cells in the G2/S phase of the cell cycle. Curcumin-induced cell death was neither due to apoptosis nor to any significant change in the expression of apoptosis-related genes, including Bcl-2, p53, cyclin B and transglutaminase. Overall our results suggest that curcumin is a potent antiproliferative agent for breast tumor cells and may have potential as an anticancer agent.

ISSN:0959-4973    

出版商:OVID    

年代:1997

数据来源: OVID