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  • 1
    Digitale Medien
    Digitale Medien
    Small cell carcinoma of the anus in a human HIV carrier: Report of a case (1993)
    Springer
    Surgery today 23 (1993), S. 85-88 
    Details
    ISSN: 1436-2813
    Schlagwort(e): small cell carcinoma ; anorectal tumor ; human immunodeficiency virus (HIV) ; acquired immunodeficiency syndrome (AIDS)
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract We report herein a rare case of metastatic anal small cell neuroendocrine carcinoma in a human immunodeficiency virus (HIV) carrier. This is only the third case of an HIV infection associated with the rare anorectal small cell carcinoma to be reported in the world literature. Although radiation and abdominoperineal resection cannot provide a cure, systemic chemotherapy consisting of cisplatin and etoposide (VP-16) achieved complete resolution of all the indicator lesions. The values of the T-helper:T-suppressor (OKT4:OKT8) ratio and β2-microglobulin showed that the state of immunodeficiency caused by the HIV did not become worse during either major surgery or systemic chemotherapy.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00309007
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  • 2
    Digitale Medien
    Digitale Medien
    Prediction of the antitumor activity of new platinum analogs based on their ex vivo pharmacodynamics as determined by bioassay (1991)
    Springer
    Cancer chemotherapy and pharmacology 27 (1991), S. 263-270 
    Details
    ISSN: 1432-0843
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Summary We report the predictive model for the clinical response of new platinum analogs against lung cancer by a bioassay using human lung-cancer cell lines including small-cell (SCLC) and non-small-cell lung cancer (NSCLC). Exponentially growing cells of six different SCLC and sic NSCLC lines were exposed to different concentrations of the three platinum compounds, cisplatin, carboplatin, and 254-S in a double-agar colony-forming cell assay. The concentrations inhibiting 50% of colony formation (IC50 value) for cisplatin, carboplatin and 254-S in SCLC cell lines were significantly lower than those in NSCLC cell lines. A total of 15 patients entered the pharmacological study. In all, 80 mg/m2 cisplatin, 450 mg/m2 carboplatin, and 100 mg/m2 254-S were each given to five patients by intravenous drip infusion. Bioassay as well as chemical assay was achieved by clonogenic techniques using NCI-H-69 (SCLC cell line) and PC-9 (NSCLC cell line) as target cells. Biological comparison of antitumor activity was performed on the basis of the antitumor activity of patients' plasma using the antitumor index (ATI), which was defined as the area under the percentage of colony suppression versus time curve obtained by bioassay and calculated by the trapezoidal rule. When NCI-H-69 and PC-9 were used as target cells for bioassay, colony-inhibitory activity was revealed by the ATIs. The ATIs obtained by bioassay showed better correlation than the AUCs obtained by chemical assay with the clinical response for cisplatin and carboplatin against SCLC and NSCLC, according to the following equation: [Reported Response (%)]=11.5668+0.0014×[ATI] (r=0.97). The response rates for 254-S against SCLC and NSCLC were predicted by this formula to be 40%–65% and 14%–16%, respectively. 254-S is prospectively suspected of having the same, if not more, activity then carboplatin against SCLC and of having almost the same activity as cisplatin against NSCLC.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00685110
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  • 3
    Digitale Medien
    Digitale Medien
    A prognostic-factor risk index in advanced non-small-cell lung cancer treated with cisplatin-containing combination chemotherapy (1992)
    Springer
    Cancer chemotherapy and pharmacology 30 (1992), S. 1-6 
    Details
    ISSN: 1432-0843
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Summary Prognostic factors for response and survival were retrospectively evaluated in 192 previously untreated patients with advanced non-small-cell lung cancer (NSCLC) who had received either vindesine plus cisplatin or mitomycin plus vindesine plus cisplatin as initial treatment. Univariate analysis demonstrated that squamous-cell histology, early stage, and a small number of metastatic sites were favorable prognostic factors for response to chemotherapy. Multivariate analysis using Cox's proportional hazard model indicated that the number of metastatic sites was the only significant pretreatment factor for response (P=0.0005). Multivariate regression analysis revealed that the number of metastatic sites (P=0.0002), sex (P=0.0009), serum albumen levels (P=0.0018), performance status (P=0.0026) and lactic dehydrogenase values (P=0.0026) contributed independently to survival. On the basis of these five prognostic factors, a prognostic index for survival was used to define three prognostic groupings (good, intermediate, and poor) for survival (median survival, 16.5 vs 9.4 vs 4.6 months;P=0.0001). This particular regression model should aid in the design and analysis of new treatment strategies and may be useful for indirect comparisons of different studies carried out in similar patient populations.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00686477
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  • 4
    Digitale Medien
    Digitale Medien
    Pharmacokinetics of (glycolato-0,0′)-diammine platinum (II), a new platinum derivative, in comparison with cisplatin and carboplatin (1989)
    Springer
    Cancer chemotherapy and pharmacology 23 (1989), S. 243-246 
    Details
    ISSN: 1432-0843
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Summary The pharmacokinetics of (glycolato-0,0′)-diammine platinum (II) (254-S; NSC 375101D), one of the new platinum analogues, was examined in a phase I study of this drug and compared with that of cisplatin and carboplatin. All drugs were given in short-term (30-min) i.v. drip infusions; the doses of 254-S, cisplatin, and carboplatin were 100, 80, and 450 mg/m2, respectively. Platinum concentrations in whole plasma, plasma ultrafiltrate, and urine were determined by atomic absorption spectrometry. After the infusion, the plasma concentration of total platinum for the three agents decayed biphasically. Ultrafilterable platinum in plasma decreased in a biexponential mode after infusions of 254-S and carboplatin, whereas the free platinum of cisplatin showed a monoexponential disappearance. The peak plasma concentrations and AUC for free platinum were 5.31 μg/ml and 959 μg/min per ml for 254-S, 3.09 μg/ml and 208 μg/min per ml for cisplatin, and 19.90 μg/ml and 3446 μg/min per ml for carboplatin, respectively. The mean ratio of plasma ultrafilterable platinum to total platinum were calculated, and the results showed that the protein-binding abilities of 254-S and carboplatin were almost identical. More than 50% of the 254-S was excreted in the urine within the first 480 min after its administration. Thrombocytopenia was reported as a dose-limiting toxicity for both 254-S and carboplatin. This similarity in side effects may mainly be due to the comparable pharmacokinetic behavior of these two platinum compounds.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00451649
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  • 5
    Digitale Medien
    Digitale Medien
    7-Ethyl-10-[4-(1-piperidino)-1-piperidino] carbonyloxy camptothecin: mechanism of resistance and clinical trials (1994)
    Springer
    Cancer chemotherapy and pharmacology 34 (1994), S. S112 
    Details
    ISSN: 1432-0843
    Schlagwort(e): CPT-11 ; Topoisomerase I ; Dose-limiting toxicity ; Resistance
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract The camptothecin derivative 7-ethyl-10-[4-(1-piperidino)-1-piperidino]-carbonyloxy camptothecin (CPT-11) has attracted the attention of clinicians because of its high antitumor activity against refractory solid cancers. We established two CPT-11-resistant cell lines, a non-small-cell lung-cancer cell line (PC-7/CPT-11) from the parental PC-7 line and an ovarian cancer cell line (HAC-2/CPT-11) from the parental HAC-2 line. The mechanisms of resistance to CPT-11 in PC-7/CPT-11 cells were reduced conversion of CPT-11 to its active metabolite SN-38 and point mutation of topoisomerase I. Those in HAC-2/CPT-11 cells were reduction of topoisomerase I activity and decreased sensitivity of topoisomerase to topoisomerase I inhibitors. No point mutation of the topoisomerase was observed in HAC-2/CPT-11 cells. We conducted two phase I trials using CPT-11 in combination with other anticancer agents. One was a phase I trial of CPT-11 and cisplatin given with a fixed dose of vindesine to patients with advanced non-small-cell lung-cancer and the other was a phase I study on a topoisomerase-targeting combination of CPT-11 and etoposide (VP-16) in patients with various malignant solid tumors. The results of the first trial indicated that the recommended dose of CPT-11 for phase II studies was 80 mg/m2 combined with 3 mg/m2 vindesine on days 1 and 8 and 60 mg/m2 cisplatin on day 1. In the second trial, the recommended dose of CPT-11/VP-16 given with recombinant granulocyte colony-stimulating factor (on days 4–17) was found to be 60/60 mg/m2 In both trials, diarrhea and granulocytopenia were considered to be dose-limiting toxicities.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00684874
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  • 6
    Digitale Medien
    Digitale Medien
    The influence of ageing on cisplatin pharmacokinetics in lung cancer patients with normal organ function (1995)
    Springer
    Cancer chemotherapy and pharmacology 36 (1995), S. 102-106 
    Details
    ISSN: 1432-0843
    Schlagwort(e): Cisplatin ; Ageing ; Pharmacokinetics
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract This study was performed to identify any relationship between age and cisplatin (CDDP) pharmacokinetics in lung cancer patients. CDDP was given at a dose of 80 mg/m2 by 1-h intravenous infusion to 23 lung cancer patients. All patients had normal renal, hepatic, and bone marrow functions. We measured ultrafilterable platinum (U-Pt) and total plasma platinum (T-Pt) using atomic absorption spectrometry. There was significant correlation between the age of the patients and U-Pt pharmacokinetic parameters such as the area under the plasma concentration versus time curve (AUC), total clearance (Cl), and peak plasma concentration (Cmax) as well as the AUC of T-Pt (P〈0.05). We performed univariate regression analysis to examine the influence of factors aside from age on the AUC of U-Pt and T-Pt. Creatinine and GPT levels were significantly related to the AUC of U-Pt, and creatinine clearance and creatinine concentrations were significantly related to the AUC of T-Pt. Therefore, stepwise multiple-regression models for the AUC of U-Pt and T-Pt were developed to assess an age effect. Age was consistently an independent and significant predictor of the AUC of U-Pt and T-Pt.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00689192
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  • 7
    Digitale Medien
    Digitale Medien
    The influence of ageing on cisplatin pharmacokinetics in lung cancer patients with normal organ function (1995)
    Springer
    Cancer chemotherapy and pharmacology 36 (1995), S. 102-106 
    Details
    ISSN: 1432-0843
    Schlagwort(e): Key words: Cisplatin ; Ageing ; Pharmacokinetics
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract  This study was performed to identify any relationship between age and cisplatin (CDDP) pharmacokinetics in lung cancer patients. CDDP was given at a dose of 80 mg/m2 by 1-h intravenous infusion to 23 lung cancer patients. All patients had normal renal, hepatic, and bone marrow functions. We measured ultrafilterable platinum (U-Pt) and total plasma platinum (T-Pt) using atomic absorption spectrometry. There was significant correlation between the age of the patients and U-Pt pharmacokinetic parameters such as the area under the plasma concentration versus time curve (AUC), total clearance (Cl), and peak plasma concentration (Cmax) as well as the AUC of T-Pt (P〈0.05). We performed univariate regression analysis to examine the influence of factors aside from age on the AUC of U-Pt and T-Pt. Creatinine and GPT levels were significantly related to the AUC of U-Pt, and creatinine clearance and creatinine concentrations were significantly related to the AUC of T-Pt. Therefore, stepwise multiple-regression models for the AUC of U-Pt and T-Pt were developed to assess an age effect. Age was consistently an independent and significant predictor of the AUC of U-Pt and T-Pt.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00689192
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  • 8
    Digitale Medien
    Digitale Medien
    Progress in preclinical and clinical studies for the development of new anticancer drugs in Japan, with emphasis on taxanes (1996)
    Springer
    Cancer chemotherapy and pharmacology 38 (1996), S. S11 
    Details
    ISSN: 1432-0843
    Schlagwort(e): Key words Taxane ; Anticancer drugs
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/s002800051030
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  • 9
    Digitale Medien
    Digitale Medien
    Cytogenetic effect of carboplatin on human lymphocytes (1988)
    Springer
    Cancer chemotherapy and pharmacology 21 (1988), S. 203-207 
    Details
    ISSN: 1432-0843
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Summary Carboplatin, a second generation cisplatin analogue, was tested for induction of sister chromatid exchange (SCE) as well as chromosomal aberrations in human lymphocytes in vitro and in vivo. A dose-dependent effect was observed for increased frequency of metaphases with SCE (r=0.984, P(0.001) as well as chromosomal aberrations (r=0.994, P(0.001), primarily chromatid gap or break, in vitro. SCE induction by carboplatin was less than that by cisplatin at the same concentration. When patients were treated with a single dose of carboplatin at a dose of 450 mg/m2, the frequency of SCE and chromatid type aberrations increased significantly. However, even when considering dose and peak plasma concentration in patients receiving carboplatin, it appears that the ability of carboplatin to induce SCE and chromosomal aberrations is weaker than that of cisplatin. SCE frequencies induced by carboplatin decreased with time going by, and in one patient who was tested 5 weeks after treatment, SCE frequency showed a decrease to the pretreatment level. It thus appears that carboplatin has an improved therapeutic index over the parent compound, cisplatin, because of its less mutagenic or carcinogenic hazard, in addition to the largely reduced incidence of untoward effects.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF00262770
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  • 10
    Digitale Medien
    Digitale Medien
    Y/6 chromosome translocation in a male with triple primary cancers involving the breast (1991)
    Springer
    Journal of cancer research and clinical oncology 117 (1991), S. 479-483 
    Details
    ISSN: 1432-1335
    Schlagwort(e): Constitutional chromosome translocation ; Y/6 translocation ; Triple primary cancers ; Male breast cancer
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Summary Cytogenetic studies were performed in a 72-year-old male patient with triple primary cancers including breast, skin and lung. Left breast cancer was diagnosed at the age of 46 and he received mastectomy and thoracic irradiation. Squamous cell carcinoma and Bowen's disease were diagnosed from two separated parts of a skin lesion at the age of 70. Small-cell lung cancer was diagnosed 1 year later, and he received chemotherapy and radiotherapy. Chromosome analysis was carried out on both peripheral lymphocyte and skin fibroblast cultures at the age of 72. Out of 30 fibroblast cells karyotyped at the second passage, 7 cells (23%) consistently showed a reciprocal translocation t(Y;6)(q12;p21). The same translocation was found in one of 200 cells from lymphocyte cultures. The findings suggest that the translocation t(Y;6) might be inherent in nature, and that the patient was a mosaic of 46,XY/ 46,X,t(Y;6)(q12;p21). These results highlight the constitutional chromosomal abnormality as one of the possible high-risk factors for multiple primary cancers.
    Materialart: Digitale Medien
    URL: http://dx.doi.org/10.1007/BF01612770
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