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I Bodrogi

Publications and source records attributed to I Bodrogi.

At least 37 records · Page 2Linked to original sources

Filgrastim during combination chemotherapy of patients with poor-prognosis metastatic germ cell malignancy. European Organization for Research and Treatment of Cancer, Genito-Urinary Group, and the Medical Research Council Testicular Cancer Working Party, Cambridge, United Kingdom.

PURPOSE: To determine the effect of r-metHu granulocyte colony-stimulating factor (G-CSF) on the proportion of patients with metastatic poor-prognosis malignant germ cell tumors who receive full dose-intensity combination chemotherapy. PATIENTS AND METHODS: In a phase III study patients received six cycles of BEP/EP (etoposide, and cisplatin, plus or minus bleomycin) or six cycles of BOP/VIP-B (bleomycin, vincristine, cisplatin/etoposide, ifosfamide, cisplatin, bleomycin). A subset were secondarily randomized to receive or not receive filgrastim. Filgrastim 5 microg/kg/day was administered subcutaneously on days 3 through 9 after each BOP and on days 6 through 19 after each VIP, BEP, or EP cycle. RESULTS: Eighty-five percent of 120 eligible patients randomized to filgrastim received at least six chemotherapy cycles compared with 70% of 130 patients randomized to not receive filgrastim (VCP = .003). Patients in the filgrastim-arm achieved significantly higher dose-intensities. Neutropenic fever occurred in 25 of 128 filgrastim-patients and in 38 of 129 non-filgrastim-patients (P = .052). Twelve and three toxic deaths occurred in the non-filgrastim- and filgrastim-arms, respectively. Nine of the 12 toxic deaths and all of the three toxic deaths were associated with febrile grade 4 neutropenia. Failure-free and overall survival were similar in both arms. CONCLUSION: During combination chemotherapy in patients with malignant germ cell tumors, the routine use of filgrastim significantly improved the delivery of the planned treatment schedule without effect on failure-free or overall survival. The use of filgrastim was associated with a clinically important reduction in the number of toxic deaths, confined to the experimental intensified-chemotherapy schedule. This study does not support the routine use of filgrastim during standard chemotherapy with BEP.

Adolescent↗

[Metallothionein expression as a marker of therapeutic sensitivity in the early stages of testicular cancer].

Data concerning the involvement of elevated metallothionein (MT) expression in drug resistance are obviously scattered and contrasting. The presence of the MT gene product protein was screened in 51 untreated human germ cell testicular tumours, furthermore a relationship between MT expression and clinical resistance was investigated. Using monoclonal antibody and immunoenzyme staining elevated MT level could be demonstrated in nuclei and cytoplasm of both seminomas and non seminomatous germ cell testis tumours. Thirty-one tumours (61%) showed extensive, 15 (29%) focal positive staining. In contrast teratomas expressed this antigen negatively or scarcely. The highest level of MT was stated in early stages (I, IIA) compared with progressed stages (IIB, III) (p = 0.0004). Between the high level of MT and clinical resistance a converse correlation could be shown because the resistant tumours expressed no or low, while the sensitive tumours significantly high level of MT protein which can be used as an useful marker to identify patient subgroups sensitive to anticancer therapy, at least in testis tumours.

Antineoplastic Combined Chemotherapy Protocols↗

Significance of examination of prostate-specific antigen and prostate-specific antigen density in patients with prostatic hyperplasia and prostate cancer.

Authors investigated PSA concentration and preoperative prostate volume in 113 histologically proved BPH and 31 prostatic cancer patients. PSA concentration was measured with the Hybritech kit, the prostate volume by ultrasound with the help of an ellipse and calculated by computer. There was no correlation between the age of patients and volume of the prostate, whereas a correlation was proved between marker concentration and prostate volume (p < 0.0001). The difference obtained by the correlation of the prostate volume and the PSA concentration ratio between the BPH and 31 tumorous patients (PSA density) was highly significant (0.143 vs. 0.699, p < 0.001). The use of PSAD further improves the diagnostic value of PSA.

Age Factors↗

[Correlation between p-53 expression and clinical resistance in testicular cancer].

One of the most common cellular gene which negatively regulates the cell cycle, thus functioning as tumour suppressor gene, is the p-53 gene. The presence of this mutated gene has been correlated with, the aggressiveness of several malignant neoplasmas. Expression of the p-53 gene product protein was screened in 55 untreated human germ cell testicular tumours, furthermore a relationship between p-53 expression and clinical resistance was investigated. Using monoclonal antibody and immunoenzyme staining elevated p-53 level could be demonstrated in nuclei of embryonal carcinoma (84%) and seminoma components (56%). Most of the choriocarcinoma cases showed positive staining. Teratomas expressed this antigen negatively or scarcely. In seminomas the highest level of p-53 was stated in stage I. In contrast the opposite tendency could be demonstrated in embryonal carcinomas where p-53 was ++ positive in stage III. Between the high level of p-53 and clinical resistance a converse correlation could be stated because the resistant tumours expressed no or low, the sensitive tumours high level of p-53 protein (P 0.01). These results suggest that elevated p-53 expression could be a prognostic marker of sensitivity in testis cancer.

Antibodies, Monoclonal↗

[Results of studies of prostate-specific antigen and prostate-specific antigen density in patients with prostatic hypertrophy and prostatic cancer].

The authors investigated the PSA concentration and the preoperative prostate volume of 113 histologically proved BPH and 31 prostate cancer patients. There was no correlation between the age of the patients and the volume of the prostate. Whereas, correlation was proved between the marker concentration and the prostate volume (p < 0.0001). The prostate volume and the PSA concentration ratio correlated between the BPH and tumorous patients (PSA density). The difference was highly significant (p < 0.001). The use of PSAD improves further the diagnostical value of PSA.

Aged↗

[Multidrug resistance of testicular cancers. (Detection of P-glycoprotein and MDR1 gene expression and their clinical connection)].

The most frequently reported alteration of multidrug-resistant cells is overexpression of a 170 kD glycoprotein (P-glycoprotein or P-170) encoding by the MDR1 gene family. Expression of the multidrug-resistance gene product P-glycoprotein was screened in 55 untreated human germ cell testicular tumors using monoclonal antibody (C219) and immunoenzyme staining. In samples out of 17 seminomatous germ cell testicular tumors (SGCT) 2 seminomas, and out of 38 non-seminomatous tumors (NSGCT) 20 carcinomas (15 teratomas, 4 embryonal carcinomas, 1 with Yolk sac differentiation and 1 embryonal rhabdomyosarcoma) showed high expression of P-glycoprotein. NSGCT-s, which are more refractory than seminomas to anticancer chemotherapy, frequently expressed P-glycoprotein. These immunohistochemically detected elevated P-170 expressions were correlated by the overexpression of MDR1 mRNA gene sequences. A relationship between clinical resistance and P-glycoprotein expression seems thus to exist in 4 teratomas 3 embryonal carcinomas, and 1 seminomas. A significant correlation (p < 0.02) between P-170 expression and clinical drug resistance in stage II-III germ cell testicular tumors could be demonstrated. The results suggest that a multidrug resistant phenotype may also occur and P-glycoprotein might contribute to drug resistance in testicular tumors.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

Results of salvage retroperitoneal lymphadenectomy (RLA) in the treatment of patients with nonseminomatous germ cell tumours remaining marker positive after inductive chemotherapy.

The authors describe the evidence and results obtained in 21 out of 100 patients who underwent salvage retroperitoneal lymphadenectomy for advanced testicular cancer (UICC stage II/B bulky and stage III) in the period 1982-1993, and in whom inductive chemotherapy was not followed by marker conversion. It is stated that if AFP positivity is low (titres below 100 ng/ml) salvage retroperitoneal lymphadenectomy (RLA) is of high therapeutic value, whereas in all cases with HCG positivity or AFP titres higher than 500 ng/ml tumorous death ensued without exception. In our cases viable tumour residues occurred in 81%. Salvage resection was feasible in 76%, but every incomplete resection (19%) was followed by death due to tumour. In all but one of the cases marker positivity, an indicator of therapy-resistant viable tumour residues, persisted after having used more than four PVB combinations or changes in the chemotherapeutic regimen.

Antineoplastic Agents↗

[Review of drugs used in the neutropenic period following cytostatic therapy and comparative study of doxycycline and ofloxacin in the treatment of patients with testicular cancer].

The authors compared the effectivity of doxycyclin or ofloxacin after combined chemotherapy of testicular cancer patients during the leukopenic periods. Between 1988 and 1991 200 patients were randomized and 194 were evaluated. One hundred and fifty two patients had been treated by cytostatic treatment earlier 2.5 or 2.9 times and 17 by irradiation. The average age was 30.1 in the doxycyclin group and 31.5 years in ofloxacin group. The patients characteristics in average age and previous treatments were not significant in the two groups. Doxycyclin was applied at the first day 200 mg and the following days 100 mg for 6.8 days and ofloxacin was given 2 times 100 mg day for 8.0 days. The preventive antibiotic treatment was insufficient in 16 or 6 cases requiring the the new antibiotic therapy. The development of the new infectional lesions was significantly higher in doxycyclin group and it needed the other antibiotic therapy. The condition of the patients did not require systemic antimycotic or antiviral therapy. The toxicity was lower in oflaxacin group. Tarivid is suitable for preventing the infection in neutropenic periods after the cytostatic therapy. The number of infections are decreased the completion with some penicillins. Regarding to previous cytostatic drugs the cephalosporins are suggested for prevention during the neutropenic periods.

Adult↗

[Incidence of osteoporosis and aseptic femur head necrosis following complex therapy of germ cell testicular tumors].

Between the period of 1981 and 1991 at the National Institute of Oncology 1300 patients suffering from non-seminoma testicular cancer were treated by chemotherapy. Among them 19 cases of femoral head necrosis, one side or bilateral, were observed. Authors collected and compared the data of 16 patients of osteonecrosis and 28 without it. The aim of the study was the determination of the causes of osteonecrosis and searching for possible relation between antineoplastic therapy and osteoporosis. High alcohol consumption was found in 15 cases in the osteonecrotic group, versus one among the others. Bone mineral content measurement was performed by quantitative computed tomography. Average ages at the time of densitometry: osteonecrotic group 39.17, patients without osteonecrosis 33.91. The relative bone mineral content was found 65.94% in the osteonecrosis (A) group and 77.92% in the group without osteonecrosis. A significant difference was found in the level of serum calcium and the steroid dose applied during chemotherapy.

Adult↗

A study of children, fathered by men treated for testicular cancer, conceived before, during, and after chemotherapy.

One hundred fifty children of 113 fathers with testicular tumour treated from 1979 on the National Institute of Oncology, Budapest, were studied. Three groups were formed on the basis of the time of conception; 69 children were born before the illness of the fathers, 40 during the 12 pretreatment months, and 41 during or after combined chemotherapy. One hundred fifty control children underwent tonsillectomy/appendectomy, but were otherwise healthy. They were matched according to age, sex, and place of inhabitance with index children. Family anamnesis, perinatal, and gestational data were listed; thereafter, physical, laboratory, immunological, and, if required, radiological examinations were made. No difference was detectable in the somatic and psychiatric status of the three groups, and development was well balanced, corresponding to age. Protocols of the combined chemotherapy applied, and the incidence of anomalies, abnormalities, malignancies, and other diseases was recorded. Incidence was similar in all three groups. Incidence of congenital malformations was not increased in children conceived before and after therapy; however, a complex congenital abnormality, an atrial septal defect with horseshoe kidney, occurred in one young girl, conceived after the end of her father's treatment. The interval between conception and the end of therapy was established in the case of children conceived either during or after therapy. This was shorter in the case of healthy children; the number of healthy children conceived during cytostatic treatment was also remarkable. Further detailed analysis of data and individual evaluation of case reports are recommended.

Adult↗

Cisplatin containing combination chemotherapy of advanced germ cell line testicular tumours.

One hundred ninety patients with germ cell line testicular tumours were treated according to the modified Einhorn scheme. The response rate was 67.9%. The most favourable results were found in the embryonal histologic type (RR = 76.9%) in the biological markers (beta-HCG and AFP) negative (RR = 97.4%) and in the minimal pulmonary extent group (RR = 94.1%). The authors treated 112 patients with including these VPB-resistant germ cell testicular tumour and those with recurrence after this treatment. The patients' mean age was 28.8 (limits 19 to 44) years. Patients were given Vepeside (100 mg/m in infusion for days 1-5), Adriablastin (40 mg/m in infusion on day 1) and Cisplatin (20 mg/m in infusion) for day 1-5. The treatment resulted in CR with 18 patients (16.1%) and PR with 42 (37.5%) (RR = 53.6%). The best results were obtained with the seminoma patients who were marker-negative and had small-volume metastasis. CR developed in 4 of 7 seminoma patients (57%) and in 7 of 25 marker-negative individuals (28%), and PR developed in 11 patients (44%) (RR = 72%). Out of 12 patients with small volume metastatis four (33%) showed CR and five revealed PR (41.7%), their RR turned out to be 74.6%. The average remission period was 37 (range 4-70) months in CR but merely 6.1 (range 2-38) months in PR. It can be stated that fairly good results can be achieved with second-line VpAP treatment in case of resistance developed to primary VPB therapy or subsequent relapse. The efficacy of combined chemotherapy of Vepesed+Holoxan +/- Adriablastin as third-choice was studied in advanced testicular cancer patients refractory to, or recurrent after, first- and second-line cytostatic therapy. Between September 1981 and January 1988 49 evaluable patients were treated with Vepesid (VP-16213--100 mg/m2 days 1-5), Holoxan (40 ml/kg days 1-5), hydration, urine-alkylation + Uromitexan +/- Adriablastin (40 mg/m day 1). The single dose of Uromitexan was 20% of the daily dose of Holoxan, and the patients received it i.v. just prior to Holoxan administration (h 0), the 4 and 8 h later. Two patients got into CR and 10 to PR. The rate of remission was 24.5%. The most severe side effect was leukopenia. The elevation of BUN and se. creatinine was transient and mild. In those cases where Holoxan was not included in the first- or second-line regimens, when combined with Vepesid and Adriablastin as third-choice therapy one could achieve further improvement. In case of CR the prolongation of life is also noteworthy. The first-, second- and third-line therapy plus salvage RLA and/or pulmonary metastasectomy achieved long-term survival only in one quarter of the patients.

Adult↗

Thoracic surgery of testicular cancer patients.

Between 1 January 1980 and 31 December 1991 the authors treated 1450 patients with malignant testicular tumours. Out of them, in 42 patients aged 18-43 years with stage III non-seminoma germ cell testicular cancer, thoracic surgical interventions took place on 44 occasions since the combined cytostatic treatment did not result in a sufficient regression, or disease progression occurred. In one case the lesion was inoperable. In 43 cases successful resection was performed. In 27 cases unilateral, in two cases bilateral thoracotomy and in 15 cases median sternotomy took place. Solitary lesions were found in 26 and multiple ones in 18 cases, respectively. Two patients died in the direct postoperative phase. Forty patients were followed up for 4 to 130 months. Due to disease progression four and seven patients were lost within 12 and 12-24 months, respectively. Currently, 31 patients are alive 4 to 130 months following surgery (29 of them tumour-free, two with tumour). Based on adequate indications the thoracic surgery is justified both from diagnostic and therapeutic points of view. The metastasectomy might offer an advance in the management of these patients.

Adolescent↗

[Spontaneous and cytostatic therapy induced chromosome aberrations in testicular cancer patients].

Chromosomal aberrations were studied in peripheral blood lymphocytes from only surgery treated testicular cancer patients and treated with chemo- and/or radiotherapy. A distinct increase in spontaneous aberration frequency over the level of 27 healthy controls in 27 patients treated with surgery alone was found. Our data suggest the existence of a certain degree of chromosome instability, which may be a factor to the development of testicular tumour. The frequency of aberrant cells was much higher in 102 treated patients than in the controls. The decrease in aberrant cells was only time-dependently gradual in VPB and X-ray treated patients, while the second line combined treatment modalities caused the highest frequency of aberrant cells in the first two years after the end of courses. The possible relationship between the persistence of chromosomal aberrations and the development of malignancies are discussed in this paper.

Antineoplastic Agents↗

[K-cell activity in patients with germ cell testicular tumors. Effect of cytostatic therapy].

The antibody-dependent cell mediated cytotoxicity of peripheral blood mononuclear cells from 92 patients with germinal cell tumours and 60 healthy male controls was measured against 0, Rh(D) positive human red blood cells sensitized with anti-D antibody. To determine the maximal K-cell activity the enzym-like kinetic model of citotoxicity was employed in which maximal activity was measured in presence of target-cell excess. To avoid variation due to the individual sensitivity of target erythrocytes red blood cells were obtained from a single donor. It was demonstrated that compared to the control group the K-cell activity of patients with germinal cell tumours was significantly enhanced. Cytotoxic activity of patients with clinically detectable tumours was significantly higher than that of patients with no detectable tumour. The K-cell activity of patients with detectable tumours was significantly increased after chemotherapy.

Antineoplastic Agents↗

Persistence of chromosomal aberrations in blood lymphocytes of testicular cancer patients. II. The effect of chemotherapy and/or radiotherapy.

Chromosome aberrations were studied in peripheral blood lymphocytes from untreated testicular cancer patients and others treated with chemo- and/or radiotherapy. A distinct increase in spontaneous aberrations over the level of healthy controls was found in patients treated with surgery alone. Our data suggest the existence of a certain degree of chromosome instability which may be a factor in the development of malignancy for testicular tumours, too. The frequency of aberrant cells was much higher in treated groups than in controls, and the total of aberrations was therapy related. The frequency of aberrant cells was the highest in the first 2 years after the end of treatments similarly to the results of 3 serially examined individuals. The decrease in aberrant cells was time-dependently gradual only in X-ray-treated patients. Real conclusions about the nature of therapy-related persistence of aberrant cells can be drawn from the study of a sufficient number of testicular cancer patients studied more than 1 year after the end of treatments.

Chromosome Aberrations↗

Children fathered by men treated for testicular cancer conceived before, during and after chemotherapy--examination for evidence of congenital malformations, malignancies and immunological defects.

Hundred children of 64 fathers with testicular tumour treated from 1979 on at the National Institute of Oncology, Budapest were studied. Three groups were formed on the basis of the time of conception. 59 children were born before the illness of the fathers, 19 during the 9 pretreatment months and 22 during or after combined chemotherapy. Family anamnesis, perinatal and gestational data were listed, thereafter physical, laboratory, immunological, psychiatric, and, if required, radiological examinations were made. No difference was detectable in the somatic and psychiatric status of the three groups, development was well balanced, corresponding to age. Protocols of the combined chemotherapy applied and incidence of anomalies, malformations, malignancies and other diseases were recorded. Their incidence was similar in all three groups though frequently this was higher than that of the normal population. Often cumulated incidence of severe congenital malformations was found in the group conceived after concluded therapy where twice as many girls were born as boys. The interval between conception and the end of therapy was established in the case of children conceived during and after therapy. This was shortest in the case of healthy children, the number of healthy children conceived during cytostatic treatment was also remarkable. Further compilation of data and individual evaluation of case reports is recommended.

Adult↗

Influence of luteinizing hormone-releasing hormone agonists on human mammary carcinoma cell lines and their xenografts.

The specific binding of luteinizing hormone-releasing hormone (LH-RH) agonist in estradiol-dependent MCF-7 and estradiol-independent MDA-MB-231 human breast cancer cells has been studied using [3H]Ovurelin [(D-3H-Phe6),des-Gly10-LH-RH- ethylamide]. The results of Scatchard analyses suggest the presence of a single class of receptor sites, both in cell suspensions and membrane fractions. Evaluation of these peptide receptors appears to reflect additional characteristics of biological behaviour of these human breast cancer cells. The synthetic LH-RH agonist Ovurelin [(D-Phe6),des-Gly10-LH-RH-ethylamide] can directly interfere (25-30%) with the proliferation of MDA-MB-231 human breast cancer cells in culture. The inhibitory effect of Ovurelin in vitro was negligible in the MCF-7 cell line. In the in vivo experiments the treated immunosuppressed mice bearing either MCF-7 or MDA-MB-231 xenografts responded to the high-dose LH-RH analogue Zoladex depot and Decapeptyl depot therapy. Since the MDA-MB-231 tumour was found to be ER-negative it seems possible that the regression of this xenograft results from the direct antitumor action of the LH-RH agonist.

Animals↗

[Epidemiology of germinal cell testicular tumor in Hungary].

The data of 1286 testis cancer persons were analyzed by the authors, which were identified in Hungary between 1981 and 1986. The comparison was carried out with international findings in this field. The incidence rate of testis tumor in Hungary reaches a value of 4.16/100,000 men/year, which seems to be quite near to the frequency of cases occurred in Northern-Europe. The patient's age was 32.9 year in the mean at the time of the diagnosis, and the age-specific incidence rate was the highest (11.2) between 25-34 years, according to international experiences. A significant difference was found in the frequency of testis cancer among 19 counties of Hungary. The extremely high testis cancer incidence in the county Vas (West-Hungary) requires further explanations. A seasonal pattern according to the patients birth months was shown, which did not correlate with data of other Hungarian authors concerning seasonal pattern of the undescendent testis.

Adult↗