PubMed Health⌕ Search

Biomedical subjects

R Kleinschmidt

Publications and source records attributed to R Kleinschmidt.

At least 19 recordsLinked to original sources
PubMed2006

Efficacy of a toxicity-adjusted topotecan therapy in recurrent small cell lung cancer.

The present prospective multicentre trial investigated whether topotecan, given at a starting dose of 1.25 mg.m(-2) with individual dose adjustment, can improve safety in patients with relapsed/refractory small cell lung cancer without loss of efficacy. Patients received topotecan intravenously on days 1-5, every 21 days, for up to six courses. In the absence of relevant haematotoxicities, topotecan was increased to 1.5 mg.m(-2) and reduced to 1.0 mg.m(-2) in case of severe haematotoxicities. Of 170 recruited patients, 73.2% had stage IV disease and 63.4% had platinum-containing pre-treatment. Patients received a total of 521 courses. In 72.6% of those courses, the dose remained at 1.25 mg.m(-2); in 9.1% it was reduced and in 18.3% it increased. Overall response rate was 14.1% including one complete response; 28.8% had stable disease. Median duration of response was 13.6 weeks and median survival was 23.4 weeks. Clinical benefit was obvious for sensitive as well as for refractory patients. Haematotoxicity of grade 3 or 4 was clearly lower compared with the standard dose of 1.5 mg.m(-2). In conclusion, topotecan at a dose of 1.25 mg.m(-2) appears to be as effective as the dose of 1.5 mg.m(-2), but with reduced toxicity. Since patients with recurrent small cell lung cancer have a poor prognosis, they benefit especially from good tolerability.

Aged↗
PubMed2003

Weekly docetaxel in patients with pretreated metastatic breast cancer: a phase II trial.

Docetaxel has consistently demonstrated its high activity as an antineoplastic agent in the treatment of metastatic breast cancer. However, 90% of patients receiving the recommended dose of 100 mg/m2 every 3 weeks will develop grade 3 or 4 neutropenia. Recent data suggest that the safety profile of a weekly docetaxel regimen compared favorably with the standard 3-week schedule. Thus, we initiated a phase II study to assess the efficacy and toxicity of weekly docetaxel in pretreated patients with metastatic breast cancer. Twenty patients with advanced, anthra-cycline-refractory breast cancer were included in this phase II trial. Docetaxel was administered at a starting dose of 40 mg/m2, repeated once a week for 3 consecutive weeks followed by a 1-week rest period (1 cycle). Patients were evaluated for tumor response every 8 weeks (after every other cycle). Therapy was continued for a maximum of six courses in patients showing tumor response or stable disease. Twenty patients received a total of 204 weekly infusions of docetaxel. The mean number of treatments was 10.2 (range 1-18). Eighteen patients were assessable for response. Five patients achieved a partial response and six patients showed either stable disease or a minor response. Seven patients had disease progression. The median survival was 7.8 months. Grade 3/4 leukopenia occurred in two patients. No other grade 3 or 4 hematologic toxicities were observed. The following grade 3/4 non-hematologic toxicities were seen: nausea/vomiting (one patient), infection (one patient), mucositis (two patients) and diarrhea (one patient). Three patients withdrew from the study due to dose-limiting toxicities (one due to severe neutropenia and two due to mucositis). We conclude that administration of docetaxel at a dose of 40 mg/m2 was effective and well tolerated even in heavily pretreated patients with metastatic breast cancer. This regimen is associated with only mild myelosuppression.

Adult↗
PubMed2002

Acute transient encephalopathy after paclitaxel infusion: report of three cases.

Paclitaxel (Taxol) is a diterpene plant product and antineoplastic agent that promotes the assembly of microtubules as well as stabilizing their formation by preventing depolymerization. Myelosuppression was found to be dose-limiting, but peripheral neurotoxicity is also a well known side-effect. Central nervous system toxicity is rare, probably because paclitaxel does not cross the blood-brain barrier. We observed three patients who presented with acute encephalopathy within 6 h after infusion of paclitaxel at normal doses. All patients had received prior whole brain irradiation (WBI) and one patient had prior brain metastasectomy. Computer tomography and magnetic resonance imaging showed no evidence of cerebral metastases. An effect from other organ toxicities was excluded in all patients. All recovered spontaneously within 4-6 h. From this we can conclude that paclitaxel can cause severe acute transient encephalopathy, which may occur more frequently after prior WBI and/or surgery due to alteration of small vessel function.

Aged↗
PubMed2001

Combined systemic and intraventricular chemotherapy in primary CNS lymphoma: a pilot study.

The objective was to evaluate response rate, response duration, and toxicity after systemic and intraventricular chemotherapy in primary CNS lymphoma (PCNSL). From September 1995 to September 1998, 20 consecutive patients with PCNSL (median age 64, range 27 to 71 years) were enrolled in a pilot study evaluating chemotherapy without radiotherapy. A high dose methotrexate (MTX) (cycles 1, 2, 4, 5) and cytarabine (ara-C) (cycles 3, 6) based systemic therapy (including dexamethasone, vinca alkaloids, ifosfamide, and cyclophosphamide) was combined with intraventricular MTX, prednisolone, and ara-C. Complete response was achieved in 11 and partial remission in two patients; in one response could not be determined. Four patients showed progressive disease and two (70, 71 years) died from treatment related complications. Observation time was 2 to 59 months (median 31.5 months). Kaplan-Meier estimate for median time to treatment failure (TTF) was 20.5 months, and for median survival 54 months. Systemic toxicity was mainly hematological. Ommaya reservoir infection occurred in four patients and acute transient MTX induced encephalopathy in two (subacute in another). Cognitive dysfunction possibly due to treatment was seen in only one patient after relapse and after a total of 12 cycles (six at relapse). In conclusion, primary chemotherapy based on high dose MTX and ara-C is highly efficient in PCNSL. Toxicity is manageable in patients younger than 70 years.

Adult↗
PubMed2000

Primary central nervous system lymphoma: a clinicopathological study of 28 cases.

A group of 28 consecutive patients (mean age 59 years) with primary central nervous system lymphoma (PCNSL) was treated with different regimens, including steroids only, radiotherapy (RT), chemotherapy or combinations of all. Lymphoma was classified as high grade malignant B-cell non-Hodgkin's lymphoma of the diffuse large cell type in each of these cases. RT alone led to tumour remission in more than 70 per cent, survival could be prolonged with additional chemotherapy. Thirteen patients were treated with chemotherapy alone; nine of them received a novel combined intraventricular and systemic polychemotherapy protocol based on high dose methotrexate (MTX) and high dose cytarabine (ara-C). The response rate was 90 per cent with 80 per cent complete responses. Neurotoxicity, i.e. white matter lesions associated with severe cognitive dysfunction affected both patients surviving RT more than a year and patients treated with combination RT/chemotherapy. Confluent white matter hyperintense lesions were detectable on MRI in three out of 13 patients treated with chemotherapy alone, however, cognitive dysfunction has not been detected in these patients.

Adult↗
PubMed2000

[Therapy-refractory thrombocytopenia in chronic hepatitis C].

HISTORY AND CLINICAL FINDINGS: A 74-year-old man known to be suffering from a chronic hepatitis C infection was hospitalized because of intestinal hemorrhage, multiple petechiae and suggillations. The patient had received oral anticoagulant medication after replacement of the mitral valve. The intake of oral vitamin K antagonist had been discontinued eight days before admission. EXAMINATION FINDINGS: On admission, the platelet count was 3 G/l, the Quick's test 72%. Colonoscopy revealed diffuse mucosal bleeding in the proximal colon. Bone marrow examination showed moderate hyperplasia of erythropoiesis, as well as a marked increase in megakaryocytes. DIAGNOSIS, THERAPY AND COURSE: The diagnosis was hepatitis C-associated idiopathic thrombocytopenic purpura. The administration of both immunoglobulins and prednisone failed to increase platelets sufficiently. There was also no improvement after administration of Danazol. However, six days after a single application of cyclophosphamide (2,000 mg on day 1), a continuous increase of platelets to 100 G/l was obtained, a level which has remained stable for the last 18 months. CONCLUSION: The differential diagnosis of a hepatitis C-associated autoimmune thrombocytopenia must be considered in patients with chronic hepatitis C infection and severe thrombocytopenia. In cases of refractory disease, treatment with cyclophosphamide may be successful. This is particularly appropriate if, in the case of an insufficient increase in thrombocytes following administration of immunoglobulins, the success of a splenectomy is improbable, or when a splenectomy must be excluded because of relative or absolute contraindications.

Aged↗
PubMed1999

Enhancement of antibody dependent cellular cytotoxicity (ADCC) by combination of cytokines.

Monoclonal antibodies (MAb) specific for tumor-associated antigens (TAA) can induce an immunological cellular attack of tumor cells by a process termed antibody dependent cellular cytotoxicity (ADCC). Cytokines may augment ADCC by direct activation of immune cells or by enhancement of TAA on tumor cells. Thus, we investigated whether ADCC by MAb 17-1A and BR55-2, which recognize TAA on colorectal tumor cells, can be augmented by 3-day incubation with different concentrations of IL-2, IL-4, IL-6, IL-12, IFN-alpha, IFN-gamma, GM-CSF, M-CSF, and TNF-alpha. ADCC was assessed by a new flowcytometric cytotoxicity assay (Flieger et al. Immunol Methods 1995; 180:1-13) using PKH-2 labeled HT29 cells as targets and PKH-26 labeled peripheral blood mononuclear cells from three healthy volunteers as effector cells. We found three reaction patterns with the cytokines tested: (a) cytokines, which increase ADCC (IL-2, IL-12, IFN-alpha, and IFN-gamma, which represent Thl cytokines); (b) cytokines with no effect (GM-CSF, M-CSF, and TNF-alpha); and (c) cytokines, which decrease ADCC (IL-4 and IL-6, which represent Th2 cytokines). Then, we tested cytokines that increase ADCC in combination with the other cytokines. We found that the combinations IL-2/IFN-alpha, IL-2/IFN-gamma, IL-2/IL-12, and IL-12/IFN-alpha potentiated ADCC. By contrast, IL-4 reduced the IL-2, IL-12, and IFN-alpha-induced ADCC. Since the Thl response, cooperation of monocytes and CD4 cells is involved, we plan to elucidate by magnetic cell sorting (MACS) separation techniques, which cells are involved in cytokine-induced ADCC. Our results may be useful for finding combinations of cytokines and MAb for the locoregional treatment of colorectal cancer.

Antibodies, Monoclonal↗
PubMed1999

I-131-Lipiodol therapy in liver neoplasms.

Twelve patients with liver neoplasms [10 HCC, 1 CCC, 1 multiple breast cancer metastases (BCM)] were treated by transarterial I-131-Lipiodol. Computed tomography (CT) and single photon emission CT (SPECT) showed pronounced I-131-Lipiodol accumulation in the tumor tissue in all cases. In three patients with HCC a reduction of tumor size was achieved after the first treatment. The remaining patients had big tumor masses; 5 of these (4 HCC, 1 CCC) had stable disease after the first treatment, and 2 HCC were progressive. One patient died immediately after therapy due to other reasons. The BCM proved significant reduction in number and size. Eighteen-FDG-PET (positron emission tomography with fluor-18-deoxy-glucose) and CT controls showed in part different results with pretherapeutic PET proving high interindividual variability in tumor activity. Side effects were tolerable. In summary, the therapy procedure with transarterial I-131-Lipiodol is safe and effective in tumors with moderate tumor mass.

Aged↗
PubMed1997

Oral idarubicin, dexamethasone and vincristine (VID) in the treatment of multiple myeloma.

In order to replace the central venous line necessary for continuous infusion of vincristine and doxorubicin with high-dose dexamethasone (VAD) and to avoid hospitalization, we evaluated the efficacy and toxicity of oral idarubicin, vincristine and dexamethasone (VID) in patients with multiple myeloma. Vincristine (1.6 mg/m2, max 2 mg) was given as a bolus injection on day 1. Idarubicin was given in capsules 10 mg/m2/day for days 1-4 with an intraindividual dose escalation, 40 mg dexamethasone were given on days 1-4, 9-12, 17-20. Treatment cycles were repeated every 28 days. At this interim analysis, 53 patients have been entered into the ongoing trial; 46 patients are evaluable for toxicity. The median age was 60 years (interquartile range, 52-65). 46% were primary or secondary refractory, 20% had previously been treated with VAD and 30% had previously untreated disease, 4% had two or more relapses. Four patients died within 2 months from entry and were considered as early deaths (8.7%). 45% of the 42 patients evaluable for efficacy achieved a partial remission and 26% a minor remission. The median reduction of the M-component was 43% (interquartile range, 25-64%). VID is an effective and convenient alternative to VAD even in relapsed or refractory patients.

Administration, Oral↗
PubMed1992

[Change in the etiology and sequelae of severe eye injuries. A comparison of 197 personal patient admissions with other reports from the literature].

The spectrum of severe eye-injuries has clearly changed. We have analysed the documents of 197 patients treated in our clinic from 1988-1990. Of 119 (60.4%) contusions and 78 (39.6%) perforating injuries only 25.3% were occupational accidents. A more detailed analysis showed above all an increase of sport- and leisure-injuries and a considerable decrease of traffic-injuries (4.6%). Shocking is in contrast the percentage (10.7%) of severe injuries by brutality. More details concerning the consequences of injuries are presented and compared with older statistics. From this conclusions are drawn for better prophylaxis.

Adolescent↗
PubMed1989

[The effectiveness of intratracheal antibiotic administration. Clinical, microbiologic and pharmacologic results].

In 199 artificially ventilated patients of an internal intensive care unit clinical, bacteriological and pharmacological effects of endotracheally administered gentamicin were investigated. The dose schedule was 2-4 x 40 mg gentamicin/day. The incidence of secondary achieved pneumonia was reduced from 70% to 18%. The endotracheal colonization of pathogenic microorganisms reached 29.6% concerning bacterial microorganisms and 61% concerning fungi, 51.8% of all specimen were sterile. During 4 years of investigation there were found 19 secondary resistances of different bacteria, 12 persisted. Serum concentrations of gentamicin under endotracheal administration of 40 mg in 6-h-intervals didn't reach therapeutic values. In case of renal disorder the dose interval should be prolonged to twelve hours.

Adult↗
PubMed1985

[Interpretation of electroretinographic findings in posterior uveitis].

The present paper deals with the electroretinographic findings in 30 patients with inflammatory or postinflammatory disturbances of the fundus. The alterations of the scotopic ERG depend on the localization and extent of the disease. The individual components of the ERG are affected differently. It is evident that in a high percentage of patients with unilateral disease the ERG of the fellow eye was affected as well. This might be due to an immunologic reaction. It is pointed out that further investigations are required in order to resolve the problems involved.

Chorioretinitis↗