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  • 1
    Electronic Resource
    Electronic Resource
    Pharmacokinetics and pharmacodynamics of prolonged oral etoposide in women with metastatic breast cancer (1995)
    Springer
    Cancer chemotherapy and pharmacology 37 (1995), S. 161-167 
    Details
    ISSN: 1432-0843
    Keywords: Etoposide ; Pharmacology ; Breast cancer
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The pharmacokinetics and pharmacodynamics of prolonged oral etoposide chemotherapy were investigated in 15 women with metastatic breast cancer who received oral etoposide 100 mg as a single daily dose for up to 15 days. There was considerable interpatient variability in the day 1 pharmacokinetic parameters: area under the plasma concentration time curve (AUC) (0–24 h) 1.95±0.87 mg/ml per min (mean ± SD), apparent oral clearance 60.9±21.7 ml/min per 1.73 m2, peak plasma concentration 5.6±2.5 μg/ml, time to peak concentration 73±35 min and half-life 220±83 min. However, intrapatient variability in systemic exposure to etoposide was much less with repeated doses. The intrapatient coefficient of variation (CV) of AUC for day 8 relative to day 1 was 20% and for day 15 relative to day 1 was 15%, compared to the day 1 interpatient CV of 45%. Neutropenia was the principal toxicity. Day 1 pharmacokinetic parameters were related to the percentage decrease in absolute neutrophil count using the sigmoidal Emax equation. A good fit was found between day 1 AUC and neutrophil toxicity (R 2=0.77). All patients who had a day 1 AUC〉2.0 mg/ml per min had WHO grade III or IV neutropenia. The predictive performance of the models for neutrophil toxicity was better for AUC (percentage mean predictive error 5%, percentage root mean square error 18.1%) than apparent oral clearance, peak plasma concentration, or daily dose (mg/m2). A limited sampling strategy was developed to predict AUC using a linear regression model incorporating a patient effect. Data sets were divided into training and test sets. The AUC could be estimated using a model utilizing plasma etoposide concentration at only two time points, 4 h and 6 h after oral dosing (R 2=98.9%). The equation AUCpr=−0.376+0.631×C4h+0.336×C6h was validated on the test set with a relative mean predictive error of −0.88% and relative root mean square error of 6.4%. These results suggest monitoring of AUC to predict subsequent myelosuppression as a strategy for future trials with oral etoposide.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00685644
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    Paper (German National Licenses)
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  • 2
    Electronic Resource
    Electronic Resource
    Radioenhancement by cisplatin with accelerated fractionated radiotherapy in a human tumour xenograft (1997)
    Springer
    Cancer chemotherapy and pharmacology 40 (1997), S. 534-539 
    Details
    ISSN: 1432-0843
    Keywords: Key words Cisplatin ; Radiation enhancement ; Tumour growth delay ; Xenograft ; Squamous carcinoma
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The aim of the present study was to investigate whether cisplatin would enhance the radioresponse of a human tumour xenograft when given in different schedules combined with accelerated fractionated radiation therapy. A human squamous carcinoma of the hypopharynx, FaDu, was grown in the thigh of athymic nude mice. Tumours were exposed to twice-daily 2-Gy fractions, applied 6 h apart over 2 weeks, 5 days a week, alone or combined with cisplatin given at maximally tolerated doses in three different schedules: (1) i.p. as a single bolus (SB) or (2) i.p. as a daily bolus at 30 min before the first daily radiation fraction or (3) s.c. as a continuous infusion through a mini-osmotic pump over 13 days, commencing 24 h prior to the first daily radiation fraction. The end point for the study was tumour growth delay (TGD), calculated as the difference between the delay in regrowth to 200% of the initial tumour size in treated versus control mice. SB cisplatin plus radiation showed only an additive effect on TGD, whereas daily-bolus and continuous-infusion cisplatin demonstrated a greater than additive effect when combined with accelerated fractionated radiation in this human tumour model. Cisplatin appears to be especially beneficial as a radiation enhancer when given throughout the course of radiation.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s002800050699
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    Paper (German National Licenses)
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  • 3
    Electronic Resource
    Electronic Resource
    Etoposide, carboplatin, cyclophosphamide and vincristine in previously untreated patients with small-cell lung cancer (1990)
    Springer
    Cancer chemotherapy and pharmacology 25 (1990), S. 367-370 
    Details
    ISSN: 1432-0843
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The efficacy and toxicity of 120 mg/m2 etoposide and 100 mg/m2 carboplatin given i.v. daily x 3 together with 750 mg/m2 cyclophosphamide and 14 mg/m2 vincristine given i.v. on day 1 (ECCO) in a regimen given every 28 days for 6 courses was assessed in 90 (40 limited stage, 50 extensive stage) previously untreated patients with small-cell lung cancer. Mediastinal irradiation using 50 Gy in 25 fractions was given to limitedstage patients without progression after 3 courses of chemotherapy. Cranial irradiation with 30 Gy in 10 fractions was given to all patients attaining a complete response (CR). Objective responses were seen in 83% [CR, 60%; partial response (PR), 23%] of patients with limited and 76% (CR, 22%; PR, 54%) of those with extensive disease. The median relapse-free survival for objective responders with limited disease was 13.4 months, with a median of 8.0 months for extensive-stage patients. The median relapse-free survival for patients achieving a CR was 13.4 months, with a median of 7.8 months for those undergoing a PR. The median survival was 13.3 months for patients with limited disease, with a median of 9.6 months for those with extensive disease. The median survival following a CR was 18.2 months, with a median survival of 9.9 months for those showing a PR. The combination was well tolerated, with either no nausea or nausea only (WHO grade 0 or 1) in 56% of patients and minimal mucositis, renal toxicity, neurotoxicity or ototoxicity. Neutropenia measuring 〈1.0×109 WBC/l (WHO grade 3 or 4) was seen in 74% of patients, with two deaths due to infection occurring during neutropenia. Thrombocytopenia of 〈50×109 platelets/l (WHO grade 3 or 4) occurred in 24% of patients. ECCO is a new, active, welltolerated program for previously untreated patients with small-cell lung cancer.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00686239
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    Paper (German National Licenses)
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  • 4
    Electronic Resource
    Electronic Resource
    Pharmacokinetics and pharmacodynamics of prolonged oral etoposide in women with metastatic breast cancer (1995)
    Springer
    Cancer chemotherapy and pharmacology 37 (1995), S. 161-167 
    Details
    ISSN: 1432-0843
    Keywords: Key words Etoposide ; Pharmacology ; Breast cancer
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  The pharmacokinetics and pharmacodynamics of prolonged oral etoposide chemotherapy were investigated in 15 women with metastatic breast cancer who received oral etoposide 100 mg as a single daily dose for up to 15 days. There was considerable interpatient variability in the day 1 pharmacokinetic parameters: area under the plasma concentration time curve (AUC) (0–24 h) 1.95±0.87 mg/ml per min (mean±SD), apparent oral clearance 60.9±21.7 ml/min per 1.73 m2, peak plasma concentration 5.6± 2.5 μg/ml, time to peak concentration 73±35 min and half-life 220±83 min. However, intrapatient variability in systemic exposure to etoposide was much less with repeated doses. The intrapatient coefficient of variation (CV) of AUC for day 8 relative to day 1 was 20% and for day 15 relative to day 1 was 15%, compared to the day 1 interpatient CV of 45%. Neutropenia was the principal toxicity. Day 1 pharmacokinetic parameters were related to the percentage decrease in absolute neutrophil count using the sigmoidal Emax equation. A good fit was found between day 1 AUC and neutrophil toxicity (R 2=0.77). All patients who had a day 1 AUC 〉2.0 mg/ml per min had WHO grade III or IV neutropenia. The predictive performance of the models for neutrophil toxicity was better for AUC (percentage mean predictive error 5%, percentage root mean square error 18.1%) than apparent oral clearance, peak plasma concentration, or daily dose (mg/m2). A limited sampling strategy was developed to predict AUC using a linear regression model incorporating a patient effect. Data sets were divided into training and test sets. The AUC could be estimated using a model utilizing plasma etoposide concentration at only two time points, 4 h and 6 h after oral dosing (R 2=98.9%). The equation AUCpr=−0.376+ 0.631×C4h+0.336×C6h was validated on the test set with a relative mean predictive error of −0.88% and relative root mean square error of 6.4%. These results suggest monitoring of AUC to predict subsequent myelosuppression as a strategy for future trials with oral etoposide.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s002800050382
    Location Call Number Limitation Availability
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    Paper (German National Licenses)
    Fulltext
  • 5
    Electronic Resource
    Electronic Resource
    Primary liver tumours in children in Victoria: incidence and pathology (1988)
    Springer
    Pediatric surgery international 3 (1988), S. 382-395 
    Details
    ISSN: 1437-9813
    Keywords: Liver tumours ; Children ; Incidence ; Pathology
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract This paper reviews the incidence and pathology of liver tumours in children in the State of Victoria from 1955 to 1987. Seventy-four cases were found and are believed to represent all liver tumours in the State during that time. There were 29 benign and 45 malignant tumours. The benign tumours comprised 13 haemangiomas, 12 mesenchymal hamartomas, and 4 epithelial lesions. The malignant tumours were 30 hepatoblastomas, 8 embryonal sarcomas, 4 hepatocellular carcinomas, and 3 miscellaneous tumours. The haemangiomas were more commonly cavernous. Four were associated with skin lesions and 3 of these were capillary in type. Mesenchymal hamartomas varied from predominantly solid to predominantly cystic. All, however, contained hamartomatous collections of ducts and liver cells irregularly arranged in dense fibrous tissue. The commonest malignant tumour was hepatoblastoma, and there were 15 of predominantly epithelial type and 15 of mixed epithelial and mesenchymal type. The 8 undifferentiated sarcomas of embryonal pattern were characterised by pleomorphism of cells, bizarre giant cells, and extensive mucoid stromal change. Four examples of hepatocellular carcinoma were seen. All were multifocal and no further case has been seen for the last 15 years. The 3 miscellaneous tumours were gastrinoma, rhabdoid tumour, and myofibroblastic tumour of uncertain histogenesis. Incidence was calculated for the period of review. The rate for benign tumours was 0.81 per million children per year and for malignant tumours 1.33 per million children per year. Surgery for hepatobalstoma was shown to be the most important factor in improving survival.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00173452
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    Paper (German National Licenses)
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