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Biomedical subjects

Z Mechl

Publications and source records attributed to Z Mechl.

At least 19 recordsLinked to original sources
PubMed1992

Treatment results of the thioether lipid ilmofosine in patients with malignant tumours.

In a multicentre study patients with liver metastases stratified to the histology of the primary tumour were investigated. A total of 102 patients with colorectal adenocarcinoma, non-small-cell lung cancer, pancreatic cancer, primary liver carcinoma and malignant melanoma were treated with the thioether lipid ilmofosine. The drug was administered orally as a tablet at a dosage of 150-300 mg/day (75 mg/tablet). The tolerability of ilmofosine was poor. There was a dose-limiting gastrointestinal toxicity with nausea, vomiting and loss of appetite (WHO grade II-IV) in 67% of patients. During the period of therapy (1-29 weeks, 8.5 weeks mean) no complete remission and no partial response were observed. We thus conclude that treatment with oral ilmofosine is not effective in patients with liver metastases due to various malignancies.

Adenocarcinoma↗
PubMed1992

Randomized phase II trial of high-dose 4'-epi-doxorubicin + cyclophosphamide versus high-dose 4'-epi-doxorubicin + cisplatin in previously untreated patients with extensive small cell lung cancer.

One hundred and eleven previously untreated patients with extensive small cell lung cancer were included in a prospective randomized study with the aim to assess the efficacy and tolerance of high-dose epirubicin (120 mg/m2) in combination with either cyclophosphamide (800 mg/m2; arm 1) or cisplatin (60 mg/m2; arm 2). Ninety-six patients were evaluable for response and toxicity and additional 12 patients for toxicity only. The overall response rate (CR+PR) in arm 1 and 2 were 61.4 (27/44) and 67.3% (35/52), respectively. The mean duration of remission was 4.4 months (arm 1) and 4.9 months (arm 2). The mean survival time was 6.6 months in arm 1 and 7.7 months in arm 2. WHO grade 4 toxicity was encountered in 25.5 and 15.8% of patients in arm 1 and 2, respectively. One case of cardiotoxicity resulting in the patient's death was observed in arm 1. Both combinations showed considerable antitumor activity. Toxicity was acceptable.

Adult↗
PubMed1991

Combination of idarubicin and cyclophosphamide administered orally in untreated postmenopausal breast cancer patients. A phase II study.

On the basis of results obtained with oral idarubicin administration in breast cancer, which have shown an established antitumor activity in approximately 28% of cases, this compound was combined with cyclophosphamide (also given orally) in postmenopausal patients with an unknown or negative steroid receptor status. The study comprised 45 untreated patients out of which 44 were evaluable for response and toxicity. The mean age was 62.5 years (range 51-75). The majority of patients had soft tissue (24) and visceral organ (17) metastases. Idarubicin was administered in one oral daily dose of 45 mg/m2 on day 1; the oral cyclophosphamide dose was 200 mg/m2 daily on days 3, 4, 5 and 6. An objective response to treatment was observed in 41% of patients (18/44, 95% confidence interval 28-56%). Complete remission (lung) was observed in 2 patients (5%), while 16 patients achieved a partial response. Eleven patients showed no change, while 15 patients progressed. A particularly good response was obtained in soft tissue metastases (54%, 13/24) while in visceral organs a response was achieved in 31% of patients (5/16). The remissions lasted 2-14 months (median 7 months), and median survival was 14+ months. Toxicity was mild and the treatment well tolerated. Grade I/II leukopenia was observed in 24% of patients (median WBC nadir 3,100); there were no signs of cardiotoxicity. Grade I and II alopecia was observed in 75% of patients: nausea/vomiting were present in 73% of cases. The results of this study indicate that oral administration of idarubicin and cyclophosphamide produces a valuable antitumorigenic effect in postmenopausal breast cancer patients, particularly in soft tissue metastases. Further randomized studies will be needed to evaluate this treatment approach.

Administration, Oral↗
PubMed1991

Do some malignant melanoma cells share antigens with the myeloid monocyte lineage?

Melanoma cells freshly isolated from 63 advanced primary lesions and 103 metastases were analyzed by staining with monoclonal antibodies MEM 28 directed against a 200 kDa antigen present on all leukocytes and tissue macrophages (CD 45), MEM 18 directed against a monocyte antigen of 53 kDa, anti CD 14--Immunotech, Marseille and 3.9 directed against a 150 kDa antigen expressed on monocytes and to even greater degree on most tissue macrophages (CD 11 c). All antibodies showed variable reactivity with melanoma cells, percentage of positive tumor cells ranged from 0 to 70.

Antibodies, Monoclonal↗
PubMed1990

Phase II clinical evaluation of etoposide (VP-16-213, Vepesid) as a second-line treatment in ovarian cancer. Results of the South-East European Oncology Group (SEEOG) Study.

The objective of this trial was to define the antitumor activity and toxicity of etoposide for second-line treatment of patients with bulky ovarian carcinoma. Between February 1, 1986 and November 1, 1988 we recruited 82 patients. Out of them 77 (93.9%) were evaluable for toxicity and 71 (86.6%) for response. Patient characteristics are as follows: median age 57 years (range 15-75), median performance status: WHO 1, prior chemotherapy with more than 3 drugs 24 patients, with previous cisplatin 63 patients, with previous adriamycin 47 patients, with previous irradiation plus chemotherapy 17 patients. The following treatment schedule was applied: each patient started with 150 mg/m2 of etoposide administered i.v. on days 1-3. If this first cycle was well tolerated the dosage was escalated to 200 mg/m2 days 1-3. This higher dosage was then repeated at 4-week intervals. For evaluation of response the WHO criteria were used. One patient (1.4%) achieved complete remission and 5 (7.0%) partial remission. In 48 patients (67.6%) minor response or stabilisation of the disease were observed. Seventeen patients (24%) showed no response. The median duration of remission was 5.5 months (range 2-20). The median duration of stabilisation was 3 months (range 2-24). The median survival time was 10 months with a range of 2-30 months. The myelotoxic side-effects are as follows: WBC less than 2,000 was recorded in 6 patients and greater than 1,000 in 2 patients. Thrombocytopaenia with platelet count less than 50,000 occurred in 1 patient. 26 patients had anaemia WHO grades 2 and 3. Non-haematological toxicity consisted of nausea and vomiting (WHO grade 2:20 patients and grade 3:2 patients), alopecia (WHO grades 2-3:14 and 24 patients, respectively). Though the remission rate in this trial was low, the 10-month median survival with an acceptable quality of life can be taken as a fairly good salvage therapy result.

Adolescent↗
PubMed1990

Phase II study of 4'-epi-doxorubicin in patients with untreated, extensive small cell lung cancer. South-East European Oncology Group (SEEOG).

The purpose of the study was to investigate the antitumour activity and toxicity of high dose (120 mg m-2) single agent epirubicin therapy in untreated extensive small cell lung cancer patients. Out of 80 patients entered, 71 were evaluable for both antitumour activity and toxicity, 4 only for toxicity and 5 were lost for follow-up. The drug possessed a high antitumour activity, the overall response rate was 47.9% (34/71) with 4 complete remissions (CR) and 30 partial remissions (PR). The median remission duration was 3.5 months. Particular drug activity was observed in the primary tumours, lymph nodes and pleural metastases. Toxicity (leukopenia, anaemia, vomiting, reversible rhythmic cardiac disorder, stomatitis) was mild, alopecia was registered less than in adriamycin medication. One fatal congestive heart failure occurred. The actual mean survival time calculated on the basis of the data gained from 64 patients was 7.0 months (range 2-22). The high antitumour activity and no increase in toxicity justify the incorporation of high dose epirubicin into combination therapy.

Adult↗
PubMed1990

Multinucleated tumor cells and malignant melanoma.

Multinucleated cells (MC) were counted in cell preparations obtained by dissociation of representative part of tumor lesions immediately after excision. MC were present in almost all specimens examined (39 advanced primary lesions, 90 lymph node metastases and 33 dermal plus subcutaneous metastases); in one third of the samples they were very rare (less than 1% of all cells). There were no significant differences in quantity of MC between primary tumors, node metastases and dermal plus subcutaneous metastases, between node metastases seen early in the course of the disease and those seen later, and between regional node metastases taken from Stage II patients with rapidly progressing disease and regional node metastases taken from patients of the same stage whose disease-free intervals were longer. No unique pattern of similarities or differences in quantity of MC was found when comparing autologous tumor samples excised simultaneously and/or successively during the course of the disease.

Cell Nucleus↗
PubMed1989

HLA-DR antigen expression on melanoma metastases and the course of the disease.

Melanoma cells freshly isolated from regional lymph node metastases of 59 stage II malignant melanoma patients were analyzed by indirect immunofluorescence staining with monoclonal antibody TAL 1B5, detecting the HLA-DR alpha chain. The expression of HLA-A,B,C antigens, using antibody W6/32, was also investigated in 45 of these cases. There were no substantial differences in the course of the disease with respect to the percentage of positive cells. In 13 malignant melanoma patients two to four simultaneous and/or successive metastases (both locoregional and distant-subcutaneous) were analysed for HLA-DR. With simultaneous metastases (7 cases) the percentage of HLA-DR-positive cells was mostly very similar, and in no case was there more than 25% variation. As to successive metastases (9 cases) the percentage of HLA-DR-positive cells remained practically unchanged or decreased during the course of the disease.

Adult↗
PubMed1988

Combination chemotherapy with 5-fluorouracil, oral Idarubicin, and cyclophosphamide (FIC) in metastatic breast cancer--an open phase II study.

Phase II studies of p.o. Idarubicin administration, a new daunorubicin analogue (4-demethoxy-daunorubicin), have shown antitumor activity in 23%-31% of previously treated metastatic breast cancer patients, while in untreated patients a response rate of 41% was observed. Our Phase II study has shown an overall response of 23% [1 complete response (CR), 9 partial response (PR), 10/43] with a daily dose of 15 mg/m2 p.o. on days 1,2,3. On the basis of these results we have recently included Idarubicin in combination chemotherapy of breast cancer, substituting Adriamycin by Idarubicin in an FAC schedule. Of 50 consecutive metastatic breast cancer patients who entered the study, 42 patients who received greater than 2 cycles were evaluable. There were 22 premenopausal and 20 postmenopausal patients (mean = 51 years). In 25 patients a performance status of 0-2 (ECOG) was registered and in 17 patients it was 3. Previous radiation had been administered in 34, hormonal therapy in 18, and adjuvant chemotherapy (CMF 5, CMFVP 3) in 8 patients; 22 patients had predominant metastatic sites in soft tissues, 18 in visceral organs, and 2 in the bones. The FIC schedule was administered as follows: 5-fluorouracil 500 mg/m2 i.v. days 1 and 8, Idarubicin 15 mg/m2 p.o. days 1, 2 and 3, and cyclophosphamide 500 mg/m2 i.v. day 1. An objective response was observed in 23 (5 CR, 18 PR) out of 42 patients (53%, CR 12%). Soft tissue metastases responded in 55% (12/22), visceral organs in 61% (11/18), and no response was observed in bone lesions (0/2). The median remission duration was 8 months (3-16+). Toxicity was mild, expressed mainly in the form of nausea/vomiting, grade I and II in 64% of the patients. Alopecia was very mild (grade I and II in 23% of the patients). Leukopenia grade I-II was observed in 21% of the patients. In 4 patients reversible ECG changes occurred. Left ventricular ejection fraction did not show any pathological changes. The Idarubicin-containing combination chemotherapy we have used has the following characteristics: easier administration (p.o. anthracycline, no risk of tissue extravasation), lower toxicity (cardiotoxicity, alopecia, and myelosuppression in particular), and a notable antitumor activity.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1988

DNA content and MHC class II antigen expression in malignant melanoma: clinical course.

To assess the clinical value of two comparatively new properties (DNA content and MHC class II antigen expression (HLA-DR, DP, DQ) of melanoma cells) which have been independently reported to reflect the outlook for patients with malignant melanoma, we investigated retrospectively 50 stage I nodular melanomas in two comparably homogeneous groups of 23 and 27 patients, the course of whose disease differed at five years. Flow cytometry and immunohistology were used on paraffin wax embedded archival material for the analysis of DNA ploidy and detection of class II antigens, respectively. A close association was found between class II antigen expression, detected by monoclonal antibody CR3/43 (antimonomorphic DR, DP, DQ) present in 23 of 50 (46%) melanomas and unfavourable clinical course (p less than 0.005, by log rank test), but no such association was found for DNA ploidy. It is suggested that immunohistology for MHC class II antigen expression may help to predict the behaviour of nodular melanomas whereas the prognostic value of DNA ploidy is more limited. The finding that class II positive cells are found predominantly in melanomas with a substantially increased risk of metastases has implications both for concepts of tumour heterogeneity and host immunity.

Antigens, Neoplasm↗
PubMed1988

Activity of epirubicin and dibromodulcitol in advanced breast cancer. Results of the South-East European Oncology Group Study.

The therapeutic efficacy of the combination of epirubicin + dibromodulcitol was evaluated in 108 previously treated or untreated patients with advanced breast cancer. The overall response rate was 39.8%, complete remission 3.7% (mean duration 6.3 months) and partial remission 36.1% (mean duration 3.5 months). The response was rated in function of age, menopausal status, performance status and previous therapy. Toxicity (in case of 115 patients) was evaluated according to the WHO recommendation. The similar therapeutic effectiveness and less toxicity of the above drug combination compared to ADM + DBD regimen are demonstrated.

Adult↗
PubMed1988

Skin tests with autologous cholesteryl hemisuccinate-treated tumor cells, DNCB and PPD and their relationship to prognosis in malignant melanoma patients.

Skin tests with autologous cholesteryl hemisuccinate-treated tumor cells were performed in Stage II malignant melanoma patients. In the majority of cases an evident reaction having features of delayed type hypersensitivity was noted. No significant correlation between this reactivity and subsequent course of the disease was found. The same was true for the results of DNCB and PPD skin testing. An analysis of the results of all three tests in the same patient revealed no prognostic significance of this score either.

Adult↗
PubMed1987

Phase II study of oral 4-demethoxydaunorubicin in previously treated (except anthracyclines) metastatic breast cancer patients.

Forty-eight patients with metastatic breast cancer previously treated with cytostatics (except anthracyclines) underwent peroral treatment with 4-demethoxydaunorubicin (4-DMDR), a new daunorubicin analogue. Forty-three patients received greater than or equal to 2 cycles and have been evaluated. The mean age was 54 years, with 10 premenopausal and 33 postmenopausal patients. All the patients showed progressive disease. Performance status 0-2 (ECOG score) was recorded in 34, and 3 in 7 patients. Soft tissue metastases were recorded in 23, visceral in 10 and bone in 10 patients. 4-DMDR was administered in the dose of 15 mg/m2 perorally daily, on day 1, 2 and 3 (45 mg/m2 per cycle). Since there was no severe toxicity, after 2 cycles the dosage was increased to 60 mg/m2 per cycle. The patients received 2-6 cycles (median 3) and the total cumulative dose ranged from 90 to 300 mg/m2 (median 140 mg/m2). Objective response was observed in 10 patients (1 complete remission, 9 partial remissions) with a response rate of 23% (10/43). Soft tissue metastases were most responsive (8/23-35%). Two responses were observed in visceral organs. Response lasted 2-6+ months (median 4 months). Toxic side effects have been mild with myelotoxicity (grade I-II) observed in 23% of patients. Alopecia (grade 1-15 patients, grade II and III = 4 patients) was moderate. Nausea and vomiting (grade I-II) was present in 60% of patients. In all the patients MUGA scans (left ventricular ejection fraction) were in normal range, however, reversible ECG changes have been recorded in 4 patients (grade I = 3, grade II = 1). All the changes appeared on the 3rd day of the cycle but became normal before starting a new cycle. In conclusion, it should be emphasized that 4-DMDR administered perorally (45 mg/m2 per cycle) in previously treated (except anthracycline) metastatic breast cancer patients showed antitumor efficacy with a low incidence of toxic side effects. Further clinical studies, possibly with the dose escalation in the schedule we have used, will be needed in previously untreated breast cancer patients to determine exact antitumor activity of this new daunorubicin analogue.

Administration, Oral↗
PubMed1987

Phase I-II trial of aclacinomycin A given in a four-consecutive-day schedule to patients with solid tumours. A South-East European Oncology Group (SEEOG) Study.

Aclacinomycin A (ACM) in a daily dose of 30 mg/m2 was infused over 1 h on 4 consecutive days to 50 patients. Myelotoxicity was acceptable, nausea and vomiting was frequent, hair loss was mild. Grade 1-2 cardiac rhythm abnormalities were observed in 12% of the patients. Between days 1 and 4 the heart rate and the corrected Q-T interval increased while the amplitude of the T wave decreased significantly, cardiac contractility remained unchanged. In 24 evaluable breast cancer patients 1 complete remission (4%) and 2 partial remissions (8%) lasting for only 2-3 months were seen. None of the 8 patients suffering from ovarial cancer benefitted from ACM therapy.

Aclarubicin↗
PubMed1987

The excretion of urinary enzymes, proteins and creatinine in patients receiving cisplatinum.

The sensitive parameters of tubular nephrotoxicity during 4-day chemotherapy with new combination schedule of cisplatinum and 5-fluorouracil were followed. The determinations of tubular enzymes beta-glucuronidase (GRS) and gamma-glutamyltransferase (GMT) in 24 hours urine, the excretion of creatinine and proteinuria were assayed before therapy and during 4 consecutive days of treatment. We recorded the significant increase of protein excretion and only slight increase of GMT and GRS activities after chemotherapy. The decrease of the creatinine excretion on the 3rd day of therapy was not statistically significant. Simultaneously followed serum creatinine and urea levels proved the elevation of creatinine only in 1 patient (the 1st grade according WHO classification). Our results suggest that the performed regime of chemotherapy produces only very low nephrotoxicity comparing to the 1-day administration of cisplatinum. These conclusions are confirmed also by the former examinations of GRS activities in cisplatinum therapy.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1987

Comparative evaluation of two administration schedules of cis-dichlorodiammineplatinum (DDP) in ovarian and head and neck cancers: a CMEA chemotherapy group study.

The therapeutic effectivity of two administration schedules of DDP were compared. The dose was either 100 mg/m2 infused for 4 h or 20 mg/m2 infused for 1 h on 5 consecutive days. The combined objective remission rate of the two regimens were 37/53 (23% CR ++ 44% PR) for ovarian cancer and 8/35 (9% CR + 14% PR) for head and neck cancer. WHO Grade 1-2 myelo- and nephrotoxicity was observed in 26% and 20%, respectively, out of the 105 cases evaluable for toxicity in the two groups. Nausea and vomiting was moderate to severe. Neither the remission rate nor the toxicity of the two schedules were significantly different.

Adult↗
PubMed1986

Relation between dose, plasma concentration and toxicity in a phase I trial using high dose intermittent administration of an alkylating agent, diacetyldianhydrogalactitol (DADAG).

Diacetyldianhydrogalactitol (DADAG), a new alkylating sugar alcohol derivative, was administered as single, 30-min infusions in doses ranging from 390 to 1200 mg/m2. The dose-limiting toxicity was myelosuppression. The median times to WBC nadir and regeneration were 16 and 21 days, and to platelet nadir and recovery 20 and 27, respectively. Nausea and vomiting occurred frequently and were of moderate severity. For phase II studies 900 mg/m2 DADAG given every 4-6 weeks is recommended. The area under the plasma concentration time curve (AUC) for DADAG did not increase in proportion with dose escalation; it changed only from 235.5 +/- 70.7 to 262.4 +/- 71.5 micrograms h ml-1 between doses of 690 and 1050 mg/m2. No correlations between the dose administered and the nadir values for haemoglobin concentration, WBC and platelet counts, or the number of episodes of vomiting were demonstrable in this dose range. Such an association was revealed, however, when the above biological variables were related to the individual AUC for DADAG.

Adult↗