摘要:

Recombinant human granulocyte macrophage colony-stimulating factor (rhGM-CSF) was one of the first of the myeloid growth factors to become available for clinical trials. Phase I studies have demonstrated that the optimal administration is by continuous intravenous infusion or subcutaneous injections at doses of 4–5 μg/kg/day. Phase II trials in patients with a variety of malignancies who receive rhGM-CSF after standard doses of chemotherapy have demonstrated significant reductions of the duration of leucocytopenia. Use of rhGM-CSF after high-dose chemotherapy (with or without bone marrow rescue) suggest that this agent decreases the time to recovery of a normal blood count and reduces infective complications. Results in myelodysplasia and aplastic anemia have been less encouraging. The potential value of rhGM-CSF in the treatment of a variety of other conditions including AIDS and the leukemias is being tested and the early results are discussed.

ISSN:0959-4973    

出版商:OVID    

年代:1991

数据来源: OVID

摘要:

Since the number of patients seen in a pediatric oncology center is relatively small, it is difficult to perform single drug phase two studies, even on a national base. This also probably explains the lack of information on ifosfamide, despite the fact that it has now been used for more than 10 years in pediatrics. As long as chemotherapy plays such an important role in childhood cancer it remains of the utmost importance to determine the role of ifosfamide in the treatment of young cancer patients.

ISSN:0959-4973    

出版商:OVID    

年代:1991

数据来源: OVID

摘要:

In recent years a new class of agents, the serotonin type 3 receptor antagonists, has been identified. This article reviews the preclinical, pharmacological and clinical data of ondansetron, granisetron and tropisetron, the first representatives of this group. Preclinical work showed that the drugs interfere with a variety of physiological processes, and hold promise for clinical utility in a wide range of areas. To date, these agents have proven, both in early clinical and comparative studies, to be potent antiemetic agents in patients receiving cisplatin and non-cisplatin chemotherapy as well as radiotherapy. In comparative studies the antiemetic efficacy mostly has been superior to conventional antiemetic drugs with regard to the acute chemotherapy-related symptoms; whereas their role in delayed emesis needs further investigation. This also applies for their role as an antiemetic in other types of nausea and vomiting (post-operative). Toxic effects have been modest, no extrapyramidal reactions have been reported. Potential clinical use in psychiatric disorders has been suggested, and the results of clinical trials are awaited.

ISSN:0959-4973    

出版商:OVID    

年代:1991

数据来源: OVID

摘要:

The arylmethylaminopropanediols (AMAPs) are a new class of ONA intercalators. 773U82.HCI is the second of these compounds to enter clinical trial. Significant antitumor activity for 773U82.HCI was documented in a variety of murine and human tumor models. This phase I study examined a 1-, 2− and 6-hour infusion given every 28 days. Thirty-six patients received 58 courses of drug at doses ranging from 15 mg/m2to 980 mg/m2.The dose-limiting toxicity of 773U82 HCI was hemolysis noted at 980 mg/m2. Change in color of the plasma and decreases in haptoglobin were correlated with drug concentrations of the infusate ≥3 mg/ml. Clinically significant changes in hemoglobin levels requiring blood transfusions did not occur. Neurologic toxicity occurred at 720 mg/m2with the most severe neurologic toxicity occurring in a patient with the highest peak plasma concentration (4.1 μg/ml). With an increase in duration of the infusion and amount of fluid administered, the neurologic toxicity resolved. Other toxicities included mild nausea and vomiting and a dose-related phlebitis. Pharmacokinetic studies were completed in 22 patients. The mean terminalt1/2β was 4.4 h with a mean apparent volume of distribution at steady state (Vdss) of 314 l/m2. The mean total body clearance was 72 l/h/m2. Peak plasma levels ranged from 0.04 to 4.14 μg/ml. Further studies with 773U82.HCI on this schedule at the doses studied are not recommended. Hematologic monitoring for evidence of intravascular hemolysis should be included in future studies with 773U82.HCI.

ISSN:0959-4973    

出版商:OVID    

年代:1991

数据来源: OVID

摘要:

A new dosage form (ACR-CH), a suspension of small activated carbon particles adsorbing aclarubicin, was studied for its toxicity and histopathological effects on organs in mice. The 50% lethal subcutaneous dose of ACR-CH was 83.5 mg/kg, a value 2.42 times that (34.5 mg/kg) of the aclarubicin aqueous solution. The duration of the toxic effects of ACR-CH was prolonged compared with that of the aclarubicin aqueous solution. On autopsy there was no remarkable difference in macroscopic and microscopic examinations between the two dosage forms.

ISSN:0959-4973    

出版商:OVID    

年代:1991

数据来源: OVID

摘要:

We evaluated the efficacy of epirubicin in a phase II trial in breast cancer, as well as its cardiac toxicity. The study was carried out on 40 female patients with advanced, metastatic, or recurrent breast cancer. The patients were grouped into two groups: group I received 30 mg/m2epirubicin weekly, and group II 90 mg/m2epirubicin every 3 weeks. Cardiac monitoring was by ECG, röntgenography, echocardiography and endomyocardial biopsies. Clinical results were 35.3% overall response in group I, and 50% overall response in group II. No untoward cardiac toxicities were encountered. We conclude that epirubicin is an effective agent in breast cancer with relatively little cardiac toxicity.

ISSN:0959-4973    

出版商:OVID    

年代:1991

数据来源: OVID

摘要:

The potentiating effect of metoclopramide on the tumor growth inhibition of cisplatin has been studied on human squamous cell carcinomas xenografted to nude mice. In this system, the optimal time interval for intraperitoneal administration of metoclopramide was 8 h after intraperitoneal administration of cisplatin. The optimal single dose level of metoclopramide in this study was 2 mg/kg. Metoclopramide enhanced the cytotoxic effect of cisplatin at all cisplatin doses tested between 2.5 and 7.5 mg/kg body weight. Under experimental conditions that gave optimal sensitization of cisplatin-induced cytotoxicity, there was no potentiation of the cytotoxic effect with metoclopramide in combination with carboplatin. There is great similarity in the cytotoxic action of cisplatin and carboplatin, with the main difference being a much slower rate of formation of DNA crosslink formation following carboplatin exposure. Hence the data reported here support an important role for the kinetics of formation and repairability of DNA damage as part of the mechanism of metoclopramide sensitization of platinum-containing drugs.

ISSN:0959-4973    

出版商:OVID    

年代:1991

数据来源: OVID

摘要:

This study included 120 adult patients of intermediate and high-grade non-Hodgkin's lymphoma (NHL) in clinical stages II, III and IV. They were treated at Kasr El-Aini Center of Oncology and Nuclear Medicine (NEMROCK) during the period 1984–1987, inclusive. All patients were prospectively treated using four different chemotherapy regimens: MEVP (31 patients), COPP/M (23 patients), COPP/A-V (26 patients) and CHOP (40 patients). The clinical characteristics and prognostic factors in the four groups were comparable. Fifty percent (59 patients) of the whole study group attained complete remission (CR). The highest CR was achieved with the CHOP regimen (58%) and the lowest was with MEVP (39%); the difference was statistically insignificant (p> 0.05). One third of CR relapsed during the follow-up period and two thirds remained disease-free for a median of 5 years and a range of 2 to 6 years. Eleven possible risk factors were tested for their correlation with survival. Five factors were identified as affecting survival significantly. When these five factors were subjected to stepwise regression analysis, only the quality of initial response and performance status sustained their prognostic significance. These factors were used to classify patients into three risk groups (low, intermediate, and high); the 5-year survivals were 79%, 36%, 17% respectively. When the Ann-Arbor staging system was used, no significant difference in 5-year survival was detected between stages II, III, and IV. The significance of the Ann-Arbor staging system as a prognostic indicator is questioned in G2and G3NHL. A new staging system is proposed.

ISSN:0959-4973    

出版商:OVID    

年代:1991

数据来源: OVID

摘要:

A series of metal complexes and sodium salts of substituted boranes and hydroborates was shown to have cytotoxicity in murine and human tumor screens. Most of these agents were active against the growth of L-1210, Tmolt3and Hela-S3. Selected agents demonstrated activity against the growth of monolayer human cell lines derived from solid tumors. Interestingly, many of the compounds demonstrated even lower ED50values in the solid tumor than the L-1210 leukemic screen. Four compounds, Cu2(m-CH3)3NBH2CO2)42(CH3)NBH2COOH (I), [Fe3O((CH3)3NBH2CO26(CH3OH)3]NO3CH3CN (II), cis-[Co(en)2((CH3)3N BH2CO2)2]CI 2.5 H2O 0.5 CH3OH (V), and Na(CH3)3NBH2CO20.25 CH3OH (IX) were shown preferentially to inhibit DNA synthesis of L-1210 cells with only moderate inhibition of RNA and protein synthesis. In preliminary studies these agents effectively inhibited the activities of regulatory enzymes involved in the purine pathway and nucleoside kinases resulting in the suppression of d(NTP) pool levels. The boron derivatives also caused L-1210 DNA strand scission. These drugs may act together to inhibit DNA synthesis and induce cytotoxicity.

ISSN:0959-4973    

出版商:OVID    

年代:1991

数据来源: OVID

摘要:

Lonidamine (LND) is a new drug that interferes with mitochondrial functions, thereby inhibiting cellular oxygen consumption and energy metabolism in both normal and neoplastic cells. These metabolic actions of LND seem to increase the cytotoxic effect of antitumor agents such as doxorubicin (Dx). Dx is a widely used antitumor agent, but the specific cardiac toxicity which develops at a critical cumulative dose is the major limiting factor in its long term use. So far, nothing is known about a possible synergic action of LND and Dx on the metabolism of cardiac cells. The purpose of this study was to verify in an experimental modelin vivo, whether LND could increase the toxicity of Dx on rat heart. Groups each consisting of 10 female Wistar rats (weighing 100–150 g) were injected ip with a single dose of Dx (10mg/kg), LDN (50 mg/kg), or Dx plus LND and dimethylsulfoxide (DMSO) (ratio LND:DMSO = 1/10). After 24 h, oxygen uptake (QO2) and intracellular concentrations of ATP and GTP indices of cardiac metabolic impairment, were measured on heart slices in Warburg apparatus and by high-pressure liquid chroma-tography. Dx, significantly (p< 0.01), reduced QO2(34%) and intracellular concentration of ATP and GTP (32–57%). LND alone only partially reduced cardiac QO2(23%) and intracellular ATP-GTP concentration (16–31%). By contrast, the combination of the two agents did not enhance Dx-related metabolic cardiac toxicity.

ISSN:0959-4973    

出版商:OVID    

年代:1991

数据来源: OVID