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L Plasswilm

Publications and source records attributed to L Plasswilm.

27 records · Page 2Linked to original sources
PubMed1996

Concurrent Taxol and split-course accelerated radiotherapy for advanced head and neck cancer.

AIM: The aim of this study was to investigate feasibility and toxicity of fractionated paclitaxel administration concurrently with accelerated radiotherapy in the treatment of advanced head and neck cancer. PATIENTS AND METHODS: Patients with a proven histology of inoperable head and neck carcinoma were eligible for this study. Between July 1994 and August 1995, 12 patients with stage IV (UICC) tumors were treated. Patients were required to have normal end-organ function. Exclusion criteria included: age > 70 years, metastatic disease, performance status (Karnofsky < 70), major intercurrent medical disorders, and previous chemotherapy. External radiation was delivered twice a day at 1.5 Gy per fraction, specified to the reference point (ICRU 50), with a minimum interfraction interval of 6 hours. The accelerated scheme was split into 2 courses by a rest period of 9 days (including weekends) after administration of 30 Gy within 2 weeks. After 39 days a total dose of 72 Gy was reached. Paclitaxel (30 mg/m2/d) was administered as a continuous intravenous infusion over a period of 3 hours on days 1 to 5 and 29 to 33 of radiation therapy. All patients received premedication to avoid allergic reactions and circulatory monitoring was used routinely. RESULTS: Radiochemotherapy was completed in 10 patients with 8 complete and 2 partial remissions. Most important toxicity was a short period of neutropenia, which occurred 3 to 6 days after chemotherapy and was associated with fever in 9 cases. During paclitaxel infusion there was a significant but clinically not relevant increase in blood pressure and a decrease in heart rate. No acute cardiac effects occurred and no hypersensitivity reaction was seen. CONCLUSIONS: This regimen demonstrates a high activity in locally advanced head and neck cancer. Neutropenia associated with fever was the major dose limiting toxicity.

Aged↗
PubMed1995

[Simultaneous radiochemotherapy in recurrent and metastatic breast neoplasm. Clinical experience].

BACKGROUND: To improve the quality of life for patients with recurrent and metastatic breast cancer, palliation of pain, skin and soft tissue metastases and complicating lymph node relapses are mandatory. Toxicity and efficacy of 2 simultaneous radiochemotherapy regimens was tested in this study. PATIENTS AND METHODS: From October 1989 to March 1993, 48 patients with locoregional relapse of breast carcinoma after primary mastectomy and no option for curative resection were entered in the study. Seventeen patients had additional distant metastases. Two different radiochemotherapy regimens were applied: Group A (28 patients) received a "split course" radiotherapy within 10 weeks (1.8 to 2 Gy single dose) on day 1 to 12, 29 to 40 and 57 to 68 up to a total dose of 54 Gy. Chemotherapy with 5-FU, methotrexate and cyclophosphamide was applied simultaneously with radiation. After the second and fourth week the treatment was interrupted for 2 weeks. Group B (20 patients) received "conventional" radiotherapy over 6 weeks with 1.8 to 2 Gy single and 54 Gy total dose. 5-FU and mitomycin C was applied in the first and fifth week of radiotherapy. Treatment toxicity was analyzed in 48 patients, while treatment efficacy was assessed in 44 patients with a minimum follow-up of at least 1 year. RESULTS: Overall treatment response (CR+PR) was 82% in group A (CR 21%). Five of 28 patients developed toxicities of grade 3 to 4 (EORTC/RTOG/WHO). The overall response rate in group B was 87% (CR 19%). In this group 6 of 20 patients experienced toxicities of grade 3 to 4. In both groups, the local response rate was remarkably reduced in patients with additional visceral metastases. CONCLUSIONS: Both treatment concepts achieved similar response rates. Group B patients experienced a higher toxicity rate, but treatment duration was considerably shorter. The local response rate correlated well with the extent of systemic metastatic disease.

Antibiotics, Antineoplastic↗
PubMed1994

[Supportive therapy during radiochemotherapy--prevention and therapy of infections].

BACKGROUND: In current radiooncology the consistent use of best supportive care during aggressive combined treatment protocols is indispensible. Presently the optimal management of fever in granulocytopenic patients is controversially discussed. MATERIAL AND METHODS: Based on own clinical experiences and a literature review we report about empiric antibiotic and antifungal therapy in febrile patients with granulocytopenia. Particular consideration is given to the new antifungal agent fluconazole (compared to amphotericin B) and the beta-lactamase inhibitor sulbactam. We also discuss the use of hematopoietic growth factors and selective gastrointestinal decontamination. RESULTS: In fever of unknown origin the use of a two drug antibiotic combination containing an ureidopenicillin (acyl-penicillin) and an aminoglycoside is recommended. After five days of persisting fever additional antimycotic therapy is initiated. Fluconazole shows a high response rate with only few side effects in the treatment of infections with candida albicans and cryptococcus neoformans. In the early empiric antifungal therapy it is more and more replacing amphotericin B. With encouraging results sulbactam can be combined with piperacillin or mezlocillin during radiochemotherapy. Concerning G-CSF there are no general recommendations allowed. We prefer a calculated prophylaxis for patients who receive a myelotoxic chemotherapy and have a high individual risk for severe neutropenia. During the second day of reverse isolation we start a selective decontamination of the digestive tract until white-blood-cell-count increases to more than 1000 to 1500 granulocytes/mm3. CONCLUSION: The radiooncologist should be able to completely manage prevention and treatment of infectious diseases to provide an optimal use of all new options in combined modality treatment in radiooncology.

Anti-Infective Agents↗
PubMed1992

Use of an oxygen multiwire surface electrode for the direct measurement of the distribution of alveolar PO2 at different inspired oxygen concentrations.

Experiments were performed in six anaesthetised, mechanically ventilated rabbits. After thoracotomy, a multiwire surface PO2 electrode was placed at the pleural surface by means of a special holder. The local distribution of PO2 was investigated at different values of inspired oxygen concentration (FIO2). The data were analysed in order to establish (a) whether the PO2 values measured at the lung surface reflect intra-alveolar PO2 and (b) that the distribution of these values represent real physiological differences between alveoli. The mean PO2 values were related to the calculated mean alveolar PO2 (PAO2) values (r = 0.97) indicating that it is possible to study PAO2 by local measurements. It can therefore be concluded that the technique used allows the study of the influence of different FIO2 values on the distribution of PAO2. Each local PAO2 value is the result of the corresponding local ventilation/perfusion ratio (VA/Q) therefore the distribution of PAO2 values represents the distribution of VA/Q. An increasing FIO2 causes an increasing heterogeneity of PAO2 and thus VA/Q leading to a concomitant increase in the alveolo-arterial oxygen difference. At the moment it is not possible to decide if this heterogeneity is primarily caused by heterogeneities in perfusion or ventilation. The results could throw fresh light on the effect of different ventilation procedures.

Animals↗
PubMedDate not supplied

Hypoxia-induced tumour cell migration in an in vivo chicken model.

To investigate the relationship between hypoxia, neovascularisation and tumour cell spread, experiments on the area vasculosa of the early chick embryo under different oxygen concentrations were performed in vivo. Human glioblastoma cells (U-138MG) were inoculated onto the area vasculosa and the fertilised eggs were incubated under conditions of normoxia or hypoxia. For evaluation, we performed in vivo video-microscopy of the area vasculosa and determination of microvessel density (MVD), as well as a histological examination of the fixed specimen. Under hypoxia, MVD was significantly increased compared to normoxic conditions. Only under hypoxic conditions was tumour cell spread found outside the main tumour mass and within the vessels, at times followed by the subsequent development of secondary tumour cell bulks on the area vasculosa. These data lead to the conclusion that hypoxia can stimulate tumour cell migration in this in vivo model.

Animals↗
PubMedDate not supplied

Micro-light guide spectrophotometric measurement of changes in local haemoglobin oxygenation and concentration in the rabbit lung induced by hypoxia and hyperoxia.

Due to the high flexibility of the micro-light guides used with the Erlangen micro-light guide spectrophotometer (EMPHO) the instrument can be coupled to the lung surface without interfering with the local lung mechanics. The local pressure exerted on the lung varies between 45 and 47 mg/cm2. This enables the continuous investigation of local haemoglobin oxygenation and relative local haemoglobin concentration. The effect of different inspired oxygen concentrations on local oxygen saturation of intravascular haemoglobin and relative local haemoglobin concentration was investigated in 6 rabbits. The animals were anaesthetized, intubated and artificially ventilated. After thoracotomy, a light guide was placed on the pleural lung surface and haemoglobin spectra were measured at a frequency of 5 Hz using the EMPHO. Two types of changes in the local haemoglobin concentration were observed; one was correlated with the respiratory cycle. During inspiration a decrease in relative local haemoglobin concentration was observed. Opposite changes occurred during expiration. These changes were observed with simultaneous changes in local haemoglobin oxygenation. The oxygenation increased during inspiration and decreased during expiration. The amplitude of the oxygenation changes depended on the fraction of inspired oxygen FiO2. A second type of reaction in local haemoglobin concentration was observed when the inspired oxygen concentration was decreased or increased by changing the FiO2. A decrease in the oxygen partial pressure in the inspired gas mixture (PiO2) was associated with an increase in relative local haemoglobin concentration, whereas an increase in PiO2 was accompanied by a decrease in relative local haemoglobin concentration.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMedDate not supplied

Microvessel density and endothelial cell proliferation after amifostine (Ethyol) administration in vivo.

BACKGROUND: As amifostine is rapidly metabolised by the membrane-bound and capillary alkaline phosphatase to the active metabolite WR-1065, microvessel density in normal and cancer tissue may influence the therapeutic potential of the pro-drug WR-2721. Thus, it is of interest how the administration of amifostine itself alters vascular density. MATERIALS AND METHOD: For this study fertilized eggs were used and 0.05 ml amifostine (25.7 micrograms) was injected into the area vasculosa. As controls untreated area vasculosa were examined as well as eggs treated with 0.05 ml NaCl 0.9%, 48 hr after injection the vascular density was determined by histometrical methods. Applying the LAB method we performed immunohistochemical analysis of the proliferating cell nuclear antigen of endothelial cells. RESULTS: There was a significant (p < 0.001) difference in vascular density with a mean microvessel count of 25.08 (+/- 8.45 SD) vascular intersections/mm2 in the untreated control, 30.40 (+/- 12.84 SD) in the NaCl control and 53.69 (+/- 24.56 SD) in the amifostine treated area. There was also a significant (p < 0.001) difference in endothelial cell proliferation (PCNA) between untreated controls with a mean PCNA positivity of 14.05 (+/- 5.28 SD) and amifostine treated area vasculosa with a mean PCNA positivity of 32.22 (+/- 18.14 SD). CONCLUSION: A single dose administration of 25.7 micrograms amifostine induces endothelial cell proliferation and subsequent neovascularisation in the area vasculosa of the fertilised egg.

Amifostine↗
PubMedDate not supplied

Cell line and schedule-dependent cytotoxicity of paclitaxel (Taxol): role of the solvent Cremophor EL/ethanol.

BACKGROUND: Paclitaxel's optimal dosage and scheduling is currently not determined. To compare paclitaxel (PTX) cytotoxicity in vitro, three cell lines were chosen for investigation by single versus fractionated exposure to Taxol and the diluent Cremophor EL/ethanol (CEL/eth). METHODS: An exponentially growing human lung-carcinoma (SK-LU-1), human glioblastoma (U-138 MG) and mammalian fibroblast cell line (HyB14FAF28) were used for colony forming assay examining cell survival, and flow cytometric DNA analysis by measuring cell cycle development. Tested concentrations varied from 2-50 microM and were incubated for 3 and 15 hours. Single (2-50 microM/d, especially 10 microM/d), versus fractionated (2 microM/d, day 1-5) exposure of Taxol and CEL/eth was investigated. As the control population, cells were exposed to a phosphate buffered solution (PBS). RESULTS: Control populations demonstrated an average survival of 90, 99 and 93% for SK-LU-1, U-138 MG, B14, respectively. Single Taxol exposure at 10 microM showed average survival of 54, 50 and 84% after 3 hours and 9, 48 and 82% after 15 hours for the above cell lines. Fractionated Taxol exposure with 2 microM/d, days 1-5 led to average survival of 55, 86 and 63%, respectively. Single CEL/eth exposure showed a cytotoxic effect with average survival of 94, 126 and 91% after 3 hours and 47, 63 and 88% after 15 hours respectively. Fractionated CEL/eth exposure showed an average survival of 67, 94 and 65% respectively. Flow cytometric analysis detected cell cycle shift concerning S- and G2/M-phase after Taxol exposure only in the two tumour cell lines, and not in the fibroblastic cells. CEL/eth was without significant effect on cell cycle distribution in all three cell lines. CONCLUSIONS: In the two human tumour cell lines cytotoxicity was more pronounced after prolonged Taxol exposure. The fibroblast cell line was not sensitive to single treatment, and was without cell cycle changes. Comparable to Taxol the diluent CEL/eth had a significant but less pronounced cytotoxic effect. Therefore, the cytotoxic mechanisms of paclitaxel's and CEL/eth's are worthy of further investigation.

Animals↗