EPEG, a new antineoplastic epipodophyllotoxin

Creaven, Patrick J.; Allen, Larry M.

doi:10.1002/cpt1975182221

Cited by 59 publications

(14 citation statements)

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“…Penetration of etoposide into brain tumours may be partially due to a direct effect on the blood brain barrier, which is independent of the solvent system (Spigelman et al 1984). Low concentrations of etoposide and teniposide have been reported in 'third spaces' such as pleural and ascitic fluids (Canal et al 1985;Creaven & Allen 1975a;Hande et al 1984). Etoposide and its hydroxy metabolite have been detected in liver, spleen and renal tissues (Ho et al 1983;Stewart et al 1984b) and in myometrium, lung and subcutaneous tissues (D'Incalci 1985b).…”

Section: Distributionmentioning

confidence: 93%

Pharmacokinetics of Anticancer Drugs in Children

Crom

Glynn-Barnhart

Rodman

et al. 1987

Clinical Pharmacokinetics

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Interpatient pharmacokinetic variability normally observed in adults is often of even greater magnitude in paediatric patients because of age-related maturation of physiological processes responsible for drug disposition. Several antineoplastic agents have shown age-related changes, including alterations in volume of distribution, hepatic (doxorubicin, cyclophosphamide), and renal (bleomycin, methotrexate) clearances. These differences in pharmacokinetics as a function of age alter systemic exposure to chemotherapy, and may alter the efficacy and toxicity profile for standard doses of antineoplastic drugs. The relationship of systemic exposure to toxicity has been most clearly defined for methotrexate. Clinical monitoring of methotrexate serum concentrations, and adjustment of folinic acid dosages and duration of rescue based on methotrexate disposition is now routine. More recently, pharmacodynamic data have been published for high-dose methotrexate, epipodophyllotoxins, cisplatin, and cytarabine (cytosine arabinoside), indicating a relation between drug disposition and toxicity or efficacy. Collectively, these data suggest that the pharmacokinetics of many anticancer drugs in children is different from adults, and that variability in drug disposition may have an important influence on toxicity or efficacy.

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Section: Distributionmentioning

confidence: 93%

Pharmacokinetics of Anticancer Drugs in Children

Crom

Glynn-Barnhart

Rodman

et al. 1987

Clinical Pharmacokinetics

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“…Their metabolism is very complex, and still there is a great effort to clarify the qualitative and quantitative aspects related to the role of No. 6 PHARMACOKINETIC STUDIES IN LUNG CANCER -Piazza et al Total CTX is measured by gaschromatography (GC) after prior extraction and deri~atization.~*+~~ The bioavailability of CTX after oral administration is estimated at 74% to 98%,34 and the AUC is greater after an oral dose than after an equal IV dose. 35 The GC determined CTX half-life calculated with a two-compartment pharmacokinetic model is 3.9 to 8.8 hours in the a d~l t .~~,~~ CTX excretion occurs mainly in the urine, and CTXrelated hemorrhagic cystitis is probably due to its metabolite a~r o l e i n .~~ Recent research has shown that sulphydryl compounds, such as N-acetylcysteine or sodium ?LT x 103 / m 2…”

Section: Cyclophosphamide and Ifosfamidementioning

confidence: 99%

“…Their metabolism is very complex, and still there is a great effort to clarify the qualitative and quantitative aspects related to the role of No. 6 PHARMACOKINETIC STUDIES IN LUNG CANCER -Piazza et al 1189 the many metabolites. The issue is further complicated by the fact that CTX possibly induces its own metabolism and interferes with the metabolization of other drugs.3o33' Total CTX is measured by gaschromatography (GC) after prior extraction and deri~atization.~*+~~ The bioavailability of CTX after oral administration is estimated at 74% to 98%,34 and the AUC is greater after an oral dose than after an equal IV dose.…”

Section: Cyclophosphamide and Ifosfamidementioning

confidence: 99%

Pharmacokinetic studies in lung cancer patients

Piazza¹,

Cattaneo²,

Varini³

1984

Cancer

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Pharmacokinetic measurements to monitor and design cytotoxic treatments in cancer patients are being used more and more in order to optimize dosage and administration schedules. Ideally, information on drug concentrations over time should help reveal dose—response correlations. The cytotoxic drugs carmustine, etoposide, cyclophosphamide, iphosphamide, cis‐diammineplatinum, Adriamycin (doxorubicin), and 4′‐epi‐Adriamycin have been monitored on different treatment programs of patients with advanced lung cancers. The collected experience emphasizes the many individual variables encountered in clinical practice complicating the effort of correlating pharmacokinetic data with clinical results. The examples, presented on the basis of the authors' experiences, pertain to drug instability, gastrointestinal absorption, enzymatic induction in the liver, drug interaction, and drug tissue concentrations.

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“…According to Chabner (12) peak plasma levels of 14#g/ml might be achieved; Creaven (14) described lower plasma levels of 0.5-1 #g/ml. Therefore, we have investigated sensitivity at 0.4 Izg/ml and tested in a range of 0.08 20/~g/ml; 12 evaluable tumors displayed relatively flat dose-response curves (Figure 2, B).…”

Section: B Vm 26mentioning

confidence: 99%

Chemosensitivity of malignant human brain tumors

Bogdahn

1983

J Neuro-Oncol

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Tumor cell proliferation and morphological changes in tumor cells under the influence of different cytostatic agents were measured in an in vitro assay to determine chemosensitivity of human malignant brain tumors. Aliquots of 2 to 5 x 10(4) cells of a tumor cell suspension (prepared from biopsy specimen by mechanical and enzymatic disintegration) were incubated for 72 hr in the presence of different cytostatic agents. After another nine days of incubation in fresh medium, cell proliferation was calculated by incorporation of 14C-leucine and 3H-uridine and measurement in a liquid scintillation counter. Morphological changes in tumor cells were evaluated in Labtek tissue culture slides cultured under identical conditions. All drugs were tested in pharmacologically achievable concentrations. In vitro BCNU-sensitivity of 7/17 patients correlated with a postoperative recurrence free interval of 15.1 months, in vitro BCNU-resistance of 10/17 patients correlated with a postoperative recurrence free interval of 6.38 months (p less than 0.001). Tumors of lower grades of malignancy (astrocytoma III, malignant ependymoma, medulloblastoma) in our series have a statistically significant higher median BCNU-sensitivity (63.5%, p less than 0.05) and are sensitive to more drugs (3.6 drugs, median out of six selected drugs, p less than 0.01) than tumors of higher grades of malignancy (astrocytoma IV, glioblastoma multiforme; 29.54% BCNU-sensitivity, 1.4 effective drugs). In our series differences of BCNU-tumor sensitivity and number of effective drugs were not statistically significant if related to age and sex of tumor bearing patients. We think this assay provides the opportunity to test a large number of drugs in a very short period of time. Results may indicate alternative drug regimen for those patients resistant to conventional chemotherapy.

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EPEG, a new antineoplastic epipodophyllotoxin

Cited by 59 publications

References 0 publications

Pharmacokinetics of Anticancer Drugs in Children

Pharmacokinetics of Anticancer Drugs in Children

Pharmacokinetic studies in lung cancer patients

Chemosensitivity of malignant human brain tumors

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