摘要:

Breast cancer remains a major cause of morbidity and early death for women. Despite aggressive Implementation of preventive measures including screening and adjuvant therapy, this disease will likely continue to have a significant impact unless better treatments are found. A number of new agents have recently been developed that show promising results in the setting of metastatic disease including losoxantrone, vinorelbine, edatrexate, paclitaxel and docetaxel. Some have shown exciting activity where tumor progression has occurred following anthra-cycline therapy. Appropriate evaluation of new chemotherapeutic agents requires a clear description of the population studied as well as standardized assessments of outcomes. Evaluations are more relevant and more quickly done in multicenter trials. Because of the heterogeneity of metastatic breast cancer and differences in outcome measurement, randomized trials continue to be essential in defining which agents are the most appropriate candidates for further study.

ISSN:0959-4973    

出版商:OVID    

年代:1994

数据来源: OVID

摘要:

Since 5-fluorouracil (5-FU) was synthesized in the late 1950s it has become an important component of many anticancer treatment regimens. The increasing volume of literature accumulating about this drug is evidence that the optimal administration schedule and its combination with modulators has yet to be determined. Much of the investigation of 5-FU, particularly in the clinical setting, has been in the development of administration schedules based on plasma pharmacokinetic data. Particularly with the development of modulators of 5-FU, investigators are looking more closely at its intracellular tissue pharmacology and metabolism. To study the tissue metabolism of 5-FU (and other drugs), patients often have to be willing to undergo invasive procedures, sometimes with significant discomfort, usually with little direct benefit to their management. The ability to conduct an investigation of the cellular effects of a drug in both tumor and normal tissue non-invasively will not only be more acceptable to patients, resulting in better compliance to protocols, but will give information about thein situtissue which is not subject to the problems of invasive sampling techniques. Magnetic resonance spectroscopy is a non-invasive technique that has recently started to show potential in the area of investigating 5-FU metabolism and its impact on tumor and patient outcome. Further development of this method may ultimately have an impact on the investigation of any new anticancer agent.

ISSN:0959-4973    

出版商:OVID    

年代:1994

数据来源: OVID

摘要:

Treatment of human breast (MCF-7) and lung (A549) adenocarcinoma cell lines with 10 μg/ml cycloheximide provided substantial protection from paclitaxel-induced cytotoxicity. Addition of cycloheximide to cells at 0, 6, 12 or 18 h into a 24 h exposure to paclitaxel resulted in cytotoxicity similar to that found in cells treated with paclitaxel alone for only 0, 6, 12 or 18 h, respectively. DNA flow cytometry showed that paclitaxel blocked cells In G2/M. Mitotic index studies demonstrated that paclitaxel arrested cells in mitosis and that prolonged exposure to paclitaxel resulted in the development of multiple micronuclei. Concurrent Incubation of cells in cycloheximide prevented the development of a G2/M block, mitotic arrest and micronuclei formation. The addition of cycloheximide to cells at 6 or 12 h into a 24 h exposure to paclitaxel reduced the degree of G2/M block to that produced by incubation of cells in paclitaxel alone for only 6 or 12 h. Mitotic index studies confirmed that cells treated with cycloheximide during paclitaxel exposure had a marked reduction in the percentage of cells in mitosis. However, the percentage of paclitaxel-treated cells which had multiple micronuclei was increased in cells treated with cycloheximide. These results indicate that entry in to mitosis is a prerequisite for paclitaxel-induced cytotoxicity and that cycloheximide reduces cytotoxicity due to paclitaxel by preventing cells from entering mitosis. However, once cells have entered mitosis in the presence of paclitaxel, protein synthesis is not required for the development of multiple micronuclei and cytotoxicity.

ISSN:0959-4973    

出版商:OVID    

年代:1994

数据来源: OVID

摘要:

For a number of cytotoxics, a relationship between efficacy and plasma concentrations has recently been demonstrated. Lean body mass has been demonstrated to be a useful parameter for predicting drug clearance for a number of non-cytotoxic drugs. However, the role of lean body mass in predicting drug clearance for any cytotoxic drug has not been previously reported. Our purpose was to investigate lean body mass as a predictor of epirubicin clearance. Pharmacokinetic studies were performed In 10 patients receiving single agent epirubicin. Although preliminary, this study suggests that lean body should be further evaluated and tested in dose optimization studies.

ISSN:0959-4973    

出版商:OVID    

年代:1994

数据来源: OVID

摘要:

Forty patients with invasive bladder tumors were consecutively treated and followed between June 1986 and February 1993. The treatment included systemic chemotherapy combining cyclophosphamide, epirubicin and cisplatin (CEP) or methotrexate, vinblastine, epirubicin and cisplatin (M-VEP) along with intravesically applied BCG vaccine. The treatment was well tolerated by the patients. No relevant toxic effects requiring hospitalization or fatalities due to the treatment were observed. Toxic manifestations of a hematologic nature were considerably less frequent than usual, nausea and vomiting being among the most frequently observed toxic signs on the second day of application of cisplatin. The side effects resulting from intravesically applied BCG vaccine showed no significant difference in terms of severity and variety from those due to its application in superficial tumors. A median follow-up of 50.3 months (range 6–80 months) showed an objective response to the treatment as follows: complete and partial response in 27 out of 40 (67.5%) and a complete clinical response in eight out of 40 (20%). Ten patients with partial response and stabilization had complete surgical response after operative treatment. The recurrence rate in patients with a complete response and a complete surgical response was 33% (six out of 18). The survival rate was 78% at 1 year, 70% at 2 years and 68% at 4 years. A complete response to the treatment of concomitant carcinomain situwas observed in three patients. The lack of comparative and randomized studies and insufficient clinical experience did not allow an overall assessment of the therapeutic opportunities that our combined immunochemotherapy offers. The anti-tumor activity, moderate recurrence rate and comparatively good tolerance to this treatment indicate possibilities for multivariate immunochemotherapy in the treatment of invasive bladder tumors.

ISSN:0959-4973    

出版商:OVID    

年代:1994

数据来源: OVID

摘要:

Peritoneal effusion is a common complication in disseminated cancer. Intracavitary instillation of various agents has achieved control rates of 30–60% with no rational preference for one agent or another. However, serious side effects have also been observed and deaths due, for instance, to bleomycin have been reported. Mitoxantrone has recently been tested to treat effusions, and preliminary results suggest the high efficacy of this drug in the treatment of peritoneal, pericardial and pleural effusions. Nevertheless, some results have been conflicting. In the present study, 41 patients with peritoneal effusions were treated with intracavitary bleomycin or intracavitary mitoxantrone. The median duration of control of effusion was 5 months (range 1 week to 14 months) with mitoxantrone and 4 months (range 1 week to 12 months) with bleomycin. We conclude that, taking into account their limitations, both agents can be used successfully in the treatment of peritoneal effusions.

ISSN:0959-4973    

出版商:OVID    

年代:1994

数据来源: OVID

摘要:

Using dosages and a route of administration which resembled those used clinically in humans, the effects of vincristine on developing hamster embryos were evaluated. The results showed that the drug exerted a highly toxic effect in a dose-dependent manner; however, it exhibited only a sporadic teratogenic (gross malformation) effect. The data on DNA synthesis indicated involvement of internal organs and structures, which needs to be verified. Overall, the teratogenicity of the drug was more pronounced during pre-organogenesis than during the organogenesis period. It was suggested that, in contrast to the data reported in the literature, the different biological response to vincristine in hamster may relate to the use of the dose–route combination, and is potentially relevant to developmental and transplacental carcinogenesis studies.

ISSN:0959-4973    

出版商:OVID    

年代:1994

数据来源: OVID

摘要:

Tumor cells whose multidrug resistance is caused by the P-glycoprotein (Pgp) mediated anti-cancer drug (ACD) efflux can be chemosensitized by cyclosporins, whose derivatives were found to display a whole range of resistance-modulating activities. Similarly, derivatives of the non-immunosuppressive natural fungus cyclic peptolide SDZ 90–215 were recently shown to display a broad range of chemosensitizing activities. With highly resistant cells expressing high levels of Pgp, one such compound (SDZ 280–125) was shown here to restore both a normal sensitivity to the growth-inhibitory effects of ACD and a normal retention of an anthracycline antibiotic. With both read-outs, SDZ 280–125 activity was about 3-fold that of cyclosporin A (CsA). SDZ 280–125 also displayed the same profile of chemosensitization as CsA for different ACD classes.

ISSN:0959-4973    

出版商:OVID    

年代:1994

数据来源: OVID

摘要:

Mechanisms of cisplatin resistance have been studied in two independently-selected sublines expressing clinically-relevant levels of resistance (3-fold) and established from a primary testicular teratoma obtained from previously untreated patients. Resistance was not associated with any significant modification in cellular uptake of cisplatin, in total glutathione levels or associated enzyme activities. However, immunochemical quantitation of specific platinum–DNA adduct formation and removal revealed that both resistant sublines were more proficient in repairing certain adducts than their generally repair deficient respective parental lines. SUSA/CP*cells were more efficient in removing the intrastrand adducts in the sequence Pt–AG and the bifunctional Pt–(GMP)2lesions, as well as DNA-DNA inter-strand cross-links, whilst H12.1/DDP cells were highly proficient in removing the major Pt–GG intrastrand adducts.

ISSN:0959-4973    

出版商:OVID    

年代:1994

数据来源: OVID

摘要:

Ether phospholipids are new anti-neoplastic drugs that have been found active against a variety of tumor cell lines, including drug-resistant sublines. We have characterized the antiproliferative activity of three ether phospholipids, i.e. ET-18-OCH3(Edelfosine), BM 41.440 (Ilmofosine) and a new aza-derivative (BN 52205), on three leukemic cell lines, i.e. K562 (chronic myeloid leukemia, blast crisis), HL60 (promyelocytic acute leukemia) and CEM (T cell leukemia), and their respective drug-resistant sublines, i.e. K562-ADR (adryamicin resistant), HL60-DNR [daunorubicin (DNR) resistant] and CEM-VLB (vinblastin resistant). These resistant sublines have been found to express the multidrug-resistant phenotype, revealed by the presence of the P-glycoprotein (PgP) using different monoclonal antibodies. Increased cellular accumulation of the fluorescent anthracycline has been found in both sensitive and resistant cell lines after different ether phospholipid treatment times. In resistant cells, the ether phospholipid effect on DNR accumulation has also been found after blocking the PgP function by verapamil and cyclosporin A. These results confirm that the ether phospholipid action is closely linked with the membrane biochemical composition and that these new anti-tumor drugs are able to change the dynamic structural organization of the tumor cell membrane.

ISSN:0959-4973    

出版商:OVID    

年代:1994

数据来源: OVID