Biomedical subjects

R Hájek

Publications and source records attributed to R Hájek.

At least 19 recordsLinked to original sources

PubMed1997

[A new purine analog in the treatment of hematologic malignancy. I. Fludarabine].

New purine analogues, fludarabine, 2-chlorodeoxyadenosine and 2-deoxycoformycin are remarkably active in generally incurable malignant lymphoproliferative disorders. The first part of the review summarises pharmacological properties, the mechanism of action, toxicity and clinical use of fludarabine. Major clinical experience with fludarabine has been obtained in patients with chronic lymphocytic leukaemia (CLL). In the studies in pretreated patients with CLL, the overall response rate was over 50%. In previously untreated patients with CLL response rate of 75-80% was recorded with a high ratio of complete responses. Fludarabine was found to be active agent in indolent lymphoma in phase I/II. Approximately 60% of patients with follicular lymphoma respond to fludarabine monotherapy. Combination of fludarabine with cytosine arabinoside (ara-C) is now successfully used in the treatment of acute myelogenous leukaemia (AML) and myelodysplastic syndrome (MDS). Other potential areas of use for fludarabine include hairy-cell leukaemia, Waldenström's macroglobulinaemia and mycosis fungoides. Myelosupression, especially leuko and lymphopenia is the major dose-limiting adverse effect of fludarabine. A long term reduction in CD4+ T cell count may be associated with an increased incidence of opportunistic infections. Other adverse effects such as nausea and vomiting or neurotoxicity are of mild to moderate severity when the recommended dosage is used.

Antineoplastic Agents↗

PubMed1996

[Paclitaxel (Taxol)].

The paclitaxel (TAXOL); Bristol-Myers Squibb Company) represents first agent from novel class of antineoplastic drugs--taxanes to enter routine clinical practice. Paclitaxel interferes with microtubular polymerization by promoting abnormal assembly of microtubules and inhibiting their subsequent disassembly. Pharmacokinetics of paclitaxel has been intensively studied. There are indications for nonlinear pharmacokinetics when paclitaxel is administered as a short infusion and at higher doses. Neurotoxicity, mucositis, and leukopenia correlate with some pharmacokinetic parameters. The clinical development of paclitaxel was initially hampered by hypersensitivity reactions. Current dosage regiments with premedication reduced the incidence of these events to 3%. The major dose-limiting adverse effect of paclitaxel is neutropenia. Significant activities were reported especially in patients with advanced ovarian, breast, non-small cell lung cancer (NSCLC), head and neck cancer and in other types of tumours. Long-term follow-up will also allow the effects of the drug on patient survival to be determined. At present combination of Taxol (paclitaxel) with cisplatin clearly improves the duration of progression-free survival and of overall survival compared with cyclophosphamide and cisplatin in women ovarian cancer. Recently was TAXOL (paclitaxel) registered in Czech republic for treatment of patients with advanced metastatic ovarian carcinoma and in patients with metastatic breast cancer after failure of the standard therapy.

Antineoplastic Agents, Phytogenic↗

PubMed1996

[Evaluation of the cardioprotective effect of bispiperazinedione ICRF-187 (Cardioxane) in patients treated with anthracyclines--an echocardiographic study].

The cardiotoxicity of anthracycline antibiotics is a serious complication of anti-tumourous treatment. One of the possible ways how to prevent it or at least restrict it substantially is to use cardioprotective substances. The latter include ICRF-187 bispiperazinedione (dexrazoxan) which is manufactured and supplied by CHIRON Cop. under the name Cardioxane. The authors investigated by echocardiography indicators of systolic and diastolic function of the left ventricle in patients where cumulative doses of 180-240 mg/sq.m of doxorubicin were achieved. In 10 patients to whom Cardioxane was administered no changes of left ventricular function were recorded. In 18 patients treated with boluses of doxorubicin significant deterioration of left ventricular diastolic function developed. The authors provided evidence that relatively small cumulative doses of doxorubicin administered as boluses lead to impaired left ventricular diastolic function. These changes were not recorded in patients who were given the cardioprotective substance ICRF-187 (Cardioxane).

Adult↗

PubMed1996

[Treatment of multiple myeloma--melphalan monotherapy after bone marrow transplantation].

Melphalan has brought the first improvement in the therapy of multiple myeloma at the beginning of the sixties. The median of survival was prolonged from several months to three years. In the following three decades new drugs were tested, but no other drug brought better results than melphalan. The comparative studies have proved, that therapy response has been reached more rapidly after polychemotherapy than monotherapy, but none of the treatment modalities differed in the survival parameters. The significance of interferon alpha for the treatment of multiple myeloma has been tested since the beginning of the eighties. Many clinical trials have brought contraverse results. The latest metaanalysis and data published by Ludwig support the indication of interferon alpha for the multiple myeloma maintenance treatment. Important progress in the therapy of multiple myeloma has been done in the nineties. High doses of alkylating cytostatics with the support of autologous peripheral blood stem cells transplantation or bone marrow transplantation enhanced the number of therapy-responses and prolonged the survival. The results of autologous transplantations are so favourable, that this procedure can be recommended as the first line treatment in suitable patients. Allogenic bone marrow transplantation is linked with many complications and therefore this method will be performed only in a limited number of patients. Trials dealing with this new therapy-trend are reviewed in this paper.

Antineoplastic Agents, Alkylating↗

PubMed1996

[Treatment of multiple myeloma].

A new era of multiple myeloma management includes new approaches such as genetic marking and gene therapy, immunotherapy, stimulation of graft versus myeloma effect, etc. Intensive clinical research is also focused on the detection of minimal residual disease and bone marrow purging. Clinical trials have begun and the first results are promising, though preliminary. The combinations of new types of therapeutical approaches with the most efficient regimens used until now could form a new type of MM management strategy that better involves minimal residual disease.

Humans↗

PubMed1996

Evolution of multiple myeloma treatment from melphalan monotherapy to bone marrow transplantation.

Melphalan has brought the first improvement in the therapy of multiple myeloma at the beginning of the sixties. The median of survival was prolonged from several months to 3 years. In the following 3 decades new drugs were tested, but no other drug brought better results than melphalan. The comparative studies have proved, that therapy response has been reached more rapidly after polychemotherapy than after monotherapy, but none of the treatment modalities differed in the survival parameters. The significance of interferon alpha for the treatment of multiple myeloma has been tested since the beginning of the eighties. Many clinical trials have brought controversial results. The latest metaanalysis and data published support the indication of interferon alpha for the multiple myeloma maintenance treatment. Important progress in the therapy of multiple myeloma has been done in the nineties. High doses of alkylating cytostatics with the support of autologous peripheral blood stem cells transplantation or bone marrow transplantation enhanced the number of therapy-responses and prolonged the survival. The results of autologous transplantations are so favourable, that this procedure can be recommended as the first line treatment in suitable patients. Allogenic bone marrow transplantation is linked with many complications and therefore this method will be performed only in a limited number of patients. Trials dealing with this new therapy-trends are viewed in this paper.

Antineoplastic Combined Chemotherapy Protocols↗

PubMed1996

New approaches to management of multiple myeloma.

A new era of multiple myeloma (MM) management includes new approaches such as genetic marking and gene therapy, immunotherapy, stimulation of graft versus myeloma effect, etc. Intensive clinical research is also focused on the detection of minimal residual disease and bone marrow purging. Autoregulatory loop of myeloma cells and detection of genes responsible for pathological transformation of B-line cells is of great research interest. Clinical trials have begun and the first results are promising, though preliminary. The safety of the patients and the public must be major concern of all investigators. The combinations of new types of therapeutical approaches with the most efficient regimens used until now could form a new type of MM management strategy that better involves minimal residual disease.

Bone Marrow Purging↗

PubMed1996

Paclitaxel (Taxol): a review of its antitumor activity in clinical studies Minireview.

The paclitaxel represents first agent from novel class of antineoplastic drugs-taxoids. The clinical development of paclitaxel was initially hampered by hypersensitivity reactions. Current dosage regiments with premedication reduced the incidence of these side effects to less than 3%. The major dose-limiting adverse effect of paclitaxel is neutropenia. Significant activities have been reported in patients with advanced ovarian, breast, non-small cell lung cancer (NSCLC) and head and neck cancer. Combination of paclitaxel with platinum in the treatment of patients with advanced ovarian cancer has a potential to become first-line chemotherapy regimen in the treatment of this disease Long-term follow-up will also allow to determine the effect of the drug on patient survival. The promising results of this drug in the treatment of patients with other malignancies need to be confirmed in ongoing clinical studies.

Antineoplastic Agents, Phytogenic↗

PubMed1995

[Venous thrombosis in relation to central venous catheters: pathogenesis, diagnosis, therapy, possibilities of prophylaxis].

Thrombosis represents one of the most frequent and severe complication of central venous catheterization. The incidence of catheter-related venous thrombosis is not well established. This complication was found in 3.3% patients in the analysis of 23 studies with central venous access devices-ports. We have found it in 3% of our patients with implanted port. The types of catheter related thrombosis are following: mural thrombosis, fibrin sheath, thrombosis on the catheter tip. Venography has been shown to be highly reliable in identification of upper-extremity deep venous thrombosis. The up-to-date possibility of treatment and prophylaxis of venous thrombosis associated with central venous catheters are reviewed in this paper.

Catheterization, Central Venous↗

PubMed1995

[Infections in patients with central venous systems for long-term venous access: pathogenesis, classification, diagnosis and therapy].

Central venous access devices are a major source of nosocomial infection. The skin and catheter hub are the two major sources for the introduction of the colonizing organisms. Staphylococci are the leading causative agents. The authors reviews classification of catheter-related infection complications, diagnostic problems of catheter sepsis and up-to-date trends in their treatment. Diagnosis of catheter-related sepsis remains still difficult, if device is not removed. Candida catheter related is associated with higher morbidity and mortality than infections with other organisms and the device should be removed if possible. Prophylactic measures include especially a skilled team, maximal barrier precautions during insertion.

Catheterization, Central Venous↗

PubMed1995

[Present possibilities of prevention of infectious complications associated with central venous catheter systems].

Central venous access devices are a major source of nosocomial infection. The skin and catheter hub are the two major sources for the introduction of the colonizing organisms. Authors reviewed up-to-date prophylactic possibilities in this paper. Prophylactic measures include a skilled team, topical disinfectants, topical antibiotics, new types of devices such as coating catheter with antiseptic agent and catheter with silver impregnated cuffs, maximal barrier precautions during insertion, systemic vancomycin therapy of high risk patients. Exchanging central venous catheters over a guidewire might be useful diagnostically but have not been used to be of any therapeutic or prophylactic goal. Prophylactic antibiotic lock of device and use of fibrinolytic agent to clean the device may be useful but can not be a standard recommendation.

Catheterization, Central Venous↗

PubMed1995

[Subcutaneous chamber systems (ports) for long-term care in cancer patients].

Maintenance of satisfactory and safe venous access in cancer patients is part of a comprehensive care of cancer patients. As the Hickman/Broviac catheter is today used an implantable port. This port is placed in a subcutaneous pocket. The catheter connected to the port leads into the central vein, usually through the subclavian vein. An application of drugs in the port is done trough the skin. In this time could be used different types of ports, one or two chambers port, low profil port, peripheral port and others. In this paper we reported our two-years experience with 33 totally implantable access systems, which has been implanted in patients with cancer in Masaryk University Hospital Brno Bohunice. In our department was most frequently used port the nonmetallic port IMPLANTOFIX (BRAUN MELSUNGEN). All ports were in place for a total of 5,582 days, in average of 169 days. A frequency of complications were 2.15 on 1,000 days. Four ports were in place for longer than 1 year. A comparison of the incidence of complications in the present study with an analysis of 23 studies reported in literature was satisfactory. Minimal maintenance care, no restriction of life activity, improving quality of life and probably less frequency of infection complications, identify it as a significant advantage for the satisfactory maintenance of venous access of oncology patients in comparison with Hickman/Broviac catheter. Both the patients and the nursing staff showed a very high degree of satisfaction with this system. In cancer patients, especially with poor venous access, and prognosis longer than 6 months can be indicated this system with the advantage for patients.

Adolescent↗

PubMed1995

[Evaluation of treatment of anemia with erythropoietin in patients with multiple myeloma].

Multiple myeloma is very frequently associated with anaemia which has the character of hypo-proliferative anaemia of chronic diseases. In this type of anaemia the erythropoietin formation is frequently inadequate. According to data in the literature pharmacological doses of erythropoietin lead to an increase of the haemoglobin concentration in blood. Erythropoietin (Eprex Cilag) was administered to 11 patients whose haemoglobin concentration was lower than 100 g/l. The results from 10 patients were finally evaluated. During the first month all patients were given erythropoietin - 150 U/kg three times per week. Unless during the first month of treatment the haemoglobin concentration increased by 10 g/l, the dose was doubled to 300 U/kg. In patients where the haemoglobin value had risen above 120 g/l, the authors assessed an individual maintenance dose. In case three-month erythropoietin treatment did not lead to an increase of haemoglobin by 20 g/l as compared with the baseline value, erythropoietin administration was discontinued. The haemoglobin concentration increased by 20 g/l in a total of 8 (80%) of 10 evaluated patients. In all five patients where the haemoglobin concentration increased by 20 g/l during the first month, the endogenous erythropoietin concentration was less than 60 U/l. In another three patients the mentioned therapeutic response was recorded only during the 2nd or 3rd month of treatment after the erythropoietin dose had been increased. These three patients had higher baseline concentrations of endogenous erythropoietin, 100 to 350 U/l. During treatment no undesirable effects of erythropoietin were observed. Erythropoietin is a useful drug for anaemic patients with the diagnosis of multiple myeloma. According to the results of the authors work and data in the literature it is obvious that in patients with endogenous serum erythropoietin below 100 U/l a rapid riae of haemoglobin can be observed already during the first month. Patients with a higher baseline concentration of endogenous erythropoietin (100 to 500 U/l) respond less frequently to treatment and larger doses of erythropoietin must be administered. In patients with an erythropoietin value above 500 U/l there is a minimal probability that a response will be produced.

Adult↗

PubMed1995

Therapy of anemia in patients with multiple myeloma.

Multiple myeloma is very frequently associated with anemia which has the character of hypoproliferative anemia of chronic diseases. In this type of anemia there is often insufficient production of endogenous erythropoietin. According to literature pharmacological doses of erythropoietin result in the increase of blood hemoglobin concentration. Erythropoietin (Eprex Cilag) was given to 11 patients whose hemoglobin concentration in blood was lower than 100 g/l. 10 patients could be evaluated at the end of the study. Within the first month all patients were given erythropoietin in the dose of 150 U/kg 3 times a week. The dose was doubled, when the blood hemoglobin concentration did not increase by more than 10 g/l within the first month. In patients with hemoglobin level above 120 g/l we were trying to find the individual maintenance dose. In patients who had not reached a blood hemoglobin concentration increase of at least 20 g/l, as compared with the initial level, further erythropoietin administration was stopped. The concentration of hemoglobin increased of 20 g/l in 8 (80%) out of 10 patients evaluated. All 5 patients who responded within the first month, had had pretreatment concentration of endogenous erythropoietin below 60 U/l. Three other patients had not been responding before their dose of erythropoietin was increased in the 2nd and 3rd months of therapy. The therapy response appeared only in the 2nd and the 3rd months of treatment. These 3 patients had higher pretreatment concentrations of endogenous erythropoietin, from 100 to 350 U/l. During the treatment no adverse effects of erythropoietin were observed. Erythropoietin is a useful drug for anemic patients with the diagnosis of multiple myeloma. According to the results mentioned above and also according to the data from literature it is evident that in patients with the endogenous blood erythropoietin value below 100 U/l it is possible to expect a sudden rise in hemoglobin concentration already within the first month. Patients with a higher concentration of endogenous erythropoietin (100 to 500 U/l) respond to the therapy less frequently and for the increase in hemoglobin it is necessary to give higher doses of erythropoietin. Patients with the initial value of erythropoietin above 500 U/l are not likely to respond.

Adult↗

PubMed1994

[Lack of therapeutic effect on primary amyloidosis by interferon-alpha].

The therapy of primary amyloidosis is still unsatisfactory. The response rate after cytostatics, dimethylsulphoxide, colchicin and vitamin E is usually low. None of these treatment modalities prolongs significantly the survival in the majority of treated patients. The success of interferon alpha in the maintenance therapy of follicular non-Hodgkin's lymphoma and in the remission of multiple myeloma, as well as successful treatment of primary cryoglobulinemia, brought us to the idea to test interferon alfa in the therapy of primary amyloidosis. Interferon alpha-2b was administered to a patient with three years history of primary amyloidosis. Interferon alpha was used in the dose of 3 x 10(6) i. V. daily for a treatment period of 10 weeks. The evaluation of the response was based on the weekly assessment of the light chain lambda concentration in the morning spot of urine. No significant decrease of the light chain concentration during the course of the therapy was observed. The administration of interferon alpha-2b was interrupted in the 10th week of the therapy because of manic psychosis. The question is, whether a higher dose than 3 x 10(6) IU daily would be able to decrease the light chain production, or if this disease is resistant to interferon alpha therapy. Because of the low incidence of primary amyloidosis, the experiences will be collected on the base of small groups of case reports.

Amyloidosis↗

PubMed1994

[Cisplatin and carboplatin in the treatment of malignant lymphoma and multiple myeloma].

Experiences with cisplatin and carboplatin are summarized in this paper. The treatment response to monotherapy with cisplatin or carboplatin was proved in non-Hodgkin's lymphomas. This is necessary condition for the application of the drug in polychemotherapy. Cisplatin and carboplatin based combinations are not used as an initial therapy. The indications for these two drugs are primary resistant malignant lymphoma and multiple myeloma, or relapses of these diseases not responding to conventional therapy. Cisplatin based combination therapy can in these indications prolong the survival in 30-40% of patients. The role of carboplatin in malignant lymphoma is not clear yet and is under investigation. The effective antiemetic therapy (ondansetron, granisetron) miligated the fear of vomiting and therefore these combinations are used in resistant malignant lymphoproliferative diseases more then some years ago. In the tables are shown the chemotherapeutic combinations used in non-Hodgkin's lymphomas, Hodgkin disease and multiple myeloma.

Antineoplastic Combined Chemotherapy Protocols↗

PubMed1994

Treatment of refractory multiple myeloma with vincristine, adriamycin, dexamethasone, and with repeated application of cyclophosphamide (C-VAD).

The quick reduction of differentiated myeloma cells by VAD chemotherapy (vincristine, adriamycin, dexamethasone) causes, according to the investigation by Bell et al., the acceleration of the proliferation of myeloma stem cells. In 1990 Bell demonstrated that this proliferation could be stopped by administering 500 mg of cyclophosphamide in 1-week intervals. We therefore modified the classical VAD scheme to the following "C-VAD" scheme:vincristine 0.5 mg/day in continuous infusion on the first to the 4th day, adriamycin 9 mg/m2/day in continual infusion on the 1st to the 4th day, dexamethasone 40 mg p.o. or i.v. always on 4 days starting with the 1st, 10th and 20th days, cyclophosphamide 600 mg i.v. on the 5th, 10th and 20th days). A further cycle follows on the 28th day. In the present paper the effect and the tolerance of this C-VAD scheme is evaluated: In the group of 21 patients with refractory myeloma 9 remissions were achieved, 5 partial remissions, in 6 patients the disease progressed, 1 patient died after the 2nd cycle without the possibility of evaluating the therapeutic response. The mean remission length was 10.2 months. The tolerance of chemotherapy was satisfactory, C-VAD chemotherapy did not cause any serious drop in the number of leucocytes and thrombocytes. Echocardiographically lower adriamycin cardiotoxicity was demonstrated in continual administration in comparison with the bolus administration. The C-VAD scheme is considered to be suitable for comparison with the VAD chemotherapy in a randomized study.

Administration, Oral↗

PubMed1994

[Lower cardiotoxicity of adriamycin during continuous administration in patients with refractory multiple myeloma treated with cyclophosphamide, vincristine, adriamycin and dexamethasone (C-VAD)].

Standard treatment of refractory myeloma is combined VAD treatment (vincristine, adriamycin and dexamethasone). In recent years adriamycin was sometimes replaced by mitoxanthrone which caused greater myelotoxicity. As a positive feature of the exchange of adriamycin for mitoxanthrone, authors using it, report its lower cardiotoxicity. In the literature there are, however, occasional reports on a lower cardiotoxicity of adriamycin when administered in a continuous infusion. In the submitted work the authors sought answers to two questions. 1. Is the cardiotoxicity of adriamycin administered in a continuous infusion lower than the cardiotoxicity of adriamycin administered as a bolus? 2. Is it possible to add to VAD chemotherapy cyclophosphamide without increasing the toxicity excessively? After echocardiographic evaluation of the diastolic and systolic function following a cumulative dose of 200 mg the authors observed smaller changes of the above functions in the group treated with adriamycin a in a continuous infusion (patients with multiple myeloma) than in the group with bolus therapy (patients with non-Hodgkin lymphomas and acute leukaemia). Addition of 600 mg cyclophosphamide on the 5th, 10th and 20th day to the classical VAD pattern made treatment more intensive without causing a deteriorated tolerance of this treatment.

Aged↗