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Biomedical subjects

S Eckhardt

Publications and source records attributed to S Eckhardt.

At least 37 records · Page 2Linked to original sources
PubMed1994

Present research trends in cancer chemotherapy.

Those research trends which are currently in the focus of interest of various research groups are summarized. The main tendency is to look for new molecular targets and to synthesize new antitumour drugs. Moreover, new research concepts emerge out of which differentiation induction, inhibition of MDR and study of apoptosis seem to be promising. Among clinical approaches megachemotherapy, neoadjuvant treatment and progress in supportive therapy are the main research directions. Last but not least, quality of life issues of the cancer patient are of particular importance.

Animals↗
PubMed1994

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↗
PubMed1993

Epidermal growth factor-like activity and epidermal growth factor-receptors in human primary breast cancer.

Ligands binding to epidermal growth factor-receptors (EGF-Rs) as epidermal growth factor-like activity (EGF-like activity), along with EGF-R levels, were determined from human primary breast cancer samples. Receptor analysis revealed a single class of high affinity binding sites. Ng/mg protein EGF-like activity quantities were measured in cytosols, and were inversely correlated with EGF-R contents (p < 0.01), estimated by two-point assays.

Breast Neoplasms↗
PubMed1993

Attenuated veterinary virus vaccine for the treatment of cancer.

Attenuated (nonpathogenic) avian viruses have been used as a form of nonspecific immunological treatment for advanced human cancer. For this study, we used Newcastle disease virus (NDV) vaccine MTH-68/N in an open phase II/B, placebo-controlled (26 patients), multicenter clinical trial for the treatment of 33 patients with advanced cancers. NDV (4000 U/day) or placebo was administered by inhalation twice weekly. During the 6-month trial, the size and presence of primary tumors and metastases were objectively monitored at five institutions by radiologists unaware of the type of treatment that was given. Regression of tumor(s) and/or metastases were observed in eight cases treated with virus (vs. none in the placebo group; p < 0.01). Ten additional patients treated with NDV had no further progression of their tumor sizes, whereas tumor stabilization was noted in only two control patients. Objective, favorable responses (regressions plus stabilization) to virus therapy thus occurred in a total of 18 patients (55%) compared to 2 patients in the placebo group (8%; p < 0.01). Two cases of complete remission were noted in the group treated with NDV. Patients receiving virus therapy had a higher rate of survival at 1 to 2 years. Of 33 patients receiving virus vaccine, 22 survived 1 year, compared to only 4 of 26 patients in the control group (p < 0.02). After 2 years, all seven survivors in the study were in the virus therapy group. There were no 2-year survivors in the control group (p < 0.0001).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1992

Inhibition by tiazofurin of inosine 5'-phosphate dehydrogenase (IMP DH) activity in extracts of ovarian carcinomas.

Cancer cells have an increased ability to synthesize GTP (guanosine triphosphate) because of increased activity of IMP DH (inosine 5'-phosphate dehydrogenase, EC 1.1.1.205). Because IMP DH activity is rate limiting for de novo biosynthesis of GTP, this enzyme was suggested as a sensitive target for chemotherapy. Tiazofurin (2-beta-D-ribofuranosylthiazole-4-carboxamide) is converted in the cells into the active metabolite, TAD, (thiazole-4-carboxamide adenine dinucleotide) which potently inhibits IMP DH activity. By adding TAD to tissue extracts one can determine the extent of inhibition of IMP DH. We applied the IMP DH assay method to extracts of normal ovaries (N = 11) and epithelial ovarian carcinomas (N = 10). The IMP DH activity (mean +/- SE) in ovarian carcinoma was 21.1 +/- 5.8 which was markedly higher than that observed in normal ovaries (2.9 +/- 0.7 nmol/hr/mg protein) (P < 0.05%). The inhibition by TAD of IMP DH activity in ovarian carcinomas (N = 4) was 81%. The results indicate that IMP DH activity is elevated sevenfold in ovarian carcinomas as compared to normal ovary and can be inhibited by exposure to tiazofurin (TAD). Similar high IMP DH activity and inhibition of the activity by TAD was observed in patients with chronic granulocytic leukemia in blast crisis among whom 70 to 80% remissions were reported. Since there is increased IMP DH activity in human ovarian carcinomas and in OVCAR-5 cells and tiazofurin and TAD inhibit IMP DH activity of these cells and the proliferation of human ovarian carcinoma xenografts in the mouse, tiazofurin may merit serious consideration for a Phase II trial for patients with recurrent/refractory epithelial ovarian carcinoma.

Adenocarcinoma↗
PubMed1991

[The anti-estrogenic effect of 4-chloro-1,2-diphenyl-1-(4-[2-(N,N-dimethylamino)ethoxy]phenyl)1-butene (Toremifene) on the endocrine regulation in breast cancer patients].

In a combined phase I-II study the hormonal effects of Toremifene were investigated in 15-15 patients at two dose levels: 60 mg and 300 mg per os, daily. Serum estradiol, progesterone, testosterone, follicle-stimulating hormone, luteinizing hormone, prolactin, human growth hormone were monitored by radioimmunoassay and sexual hormone binding globulin by immunoradiometric assay prior to treatment and at the 2nd, 8th and 12th weeks. The influence of Toremifene upon the hypothalamo-hypophyseal axis was also controlled by a tirotropin releasing hormone functional test using 400 micrograms tirotropin releasing hormone injection iv. Estradiol, progesterone, follicle-stimulating hormone, luteinizing hormone and prolactin decreased proving the antiestrogenic activity of the drug. Sexual hormone binding globulin significantly (p less than 0.002) increased by week 12 at both doses, probably due to a direct effect of Toremifene upon the liver. The increase in sexual hormone binding globulin suggests the partial estrogenic effect of the drug. The tirotropin releasing hormone induced prolactin release was also suppressed. On the basis of hormonal changes and the clinical response of patients 60 mg of Toremifene proved to be as effective as 300 mg.

Breast Neoplasms↗
PubMed1991

Interferon alfa-2b with VMCP compared to VMCP alone for induction and interferon alfa-2b compared to controls for remission maintenance in multiple myeloma: interim results.

The present trial was designed to evaluate whether interferon (IFN) combined with standard induction chemotherapy and/or interferon remission maintenance treatment improve treatment results in patients with multiple myeloma. Up to now 89 patients have received IFN plus vincristine/melphalan/cyclophosphamide/prednisolone (VMCP) as induction therapy, and 86 conventional VMCP. The proportion of patients with progressive disease was significantly lower (P less than 0.005) under IFN + VMCP as compared to the VMCP treatment group. Survival times were significantly longer (P less than 0.02) after IFN + VMCP induction therapy than after VMCP alone. In the second phase of this investigation, 33 progression-free myeloma patients were assigned to receive IFN as maintenance therapy, and 41 patients served as untreated controls. Patients maintained with IFN showed a tendency towards increased progression-free survival. Haematological side effects were observed significantly more often in patients receiving IFN, with more severe haematological toxicity in patients on the combined IFN + VMCP regimen and an increased number of patients with mild haematological toxicity in the group maintained with IFN. Other side effects, such as fever and fatigue, remained within tolerable limits. In conclusion, the preliminary results of this current clinical trial indicate significant advantages of combined IFN + VMCP induction treatment in terms of reduced disease progression and prolonged survival and possible benefits of IFN maintenance therapy in patients with multiple myeloma.

Adult↗
PubMed1991

Treatment of resistant Hodgkin's disease with CCNU, etoposide and prednimustine (CEP).

Starting in January 1984, 63 patients with resistant Hodgkin's disease received CEP as salvage-usually third-line-chemotherapy. Complete response (CR) was achieved in 3%, partial response (PR) in 51%. The median duration of remission (CR + PR) was greater than 15 months. Treatment was generally well tolerated. Our results confirm that CEP is an effective therapeutic regimen in resistant Hodgkin's disease.

Adolescent↗
PubMed1990

Hormonal effects of toremifene in breast cancer patients.

The effect of toremifene treatment on the serum levels of sex steroids (estradiol, progesterone, testosterone), FSH, LH, prolactin, TSH, T3, T4 and SHBG was investigated. Basal prolactin level and the "prolactin reserve capacity" of the hypophysis was also studied by the TRH functional test. Steroid hormone receptors were detected in the patients where a tumor biopsy could be obtained. In a randomized trial patients were treated by 60 and 300 mg of toremifene per os, daily. Hormone levels were assayed prior to treatment and at the 2nd, 6th, 8th and 12th week of tormifene therapy. The hormonal effects of toremifene were the most marked at the 2nd and at the 8th week. Estradiol decreased continuously, SHBG increased slightly and the high initial value of basal prolactin level decreased. The TRH-induced prolactin release was suppressed by tormifene after an 8-week period. No clinical response-related tendency was found.

Adult↗
PubMed1990

Monoclonal free light chains in urine and their significance in clinical diagnostics: are they really tumor markers?

Bence Jones proteins (monoclonal free light chains of immunoglobulins) are the earliest known biological markers of malignant cell dyscrasia; Bence Jones proteinuria is also present in many types of B cell-related neoplasms. Sometimes, it may also occur in Hodgkin's disease. In some cases, benign monoclonal gammapathy was found to be associated nontumorous diseases as well. The type of monoclonal light chain, the degree of polymerization, and the isoelectric point of the molecule may affect the course of the disease. Urine samples from 637 patients with true or suspected lymphoproliferative diseases were investigated over a 2-yr period by different immunochemical methods. Bence Jones proteinuria was identified in 71 cases by isoelectric focusing combined with immunofixation, while the pathological protein was detected only in 63 cases by conventional methods. Bence Jones proteins can be detected by this new method at a level below the sensitivity of conventional procedures. Bence Jones proteins in the urine may signal a malignant tumor or malignant transformation of an earlier disease. The early detection of monoclonal immunoglobulin light chains in the urine may be important in clinical diagnosis, therapy, and follow-up.

Bence Jones Protein↗
PubMed1990

Combined treatment of anaplastic astrocytoma (grade 3-4) with diacetyl-dianhydro-galactitol (DADAG).

Autoradiographic studies of labeled diacetyldianhydro-galactitol (DADAG) with tumor bearing animals revealed that the CNS accumulates high amounts of DADAG-derived radioactivity and the elimination from the brain seems to be relatively slow. This observation and the activity of DADAG against murine ependymoblastoma classified the drug as a promising agent for the treatment of malignant brain tumors. In a series of 30 evaluable consecutive patients who were operated on for anaplastic astrocytomas, DADAG has been applied during and subsequent to postoperative radiotherapy. No severe toxicity occurred. Survivals were compared with a group of patients who got irradiation alone. Statistical analysis did not show significantly better survivals in the DADAG treated group: median value was 46.5 weeks, p = 0.232.

Adult↗
PubMed1990

Early detection of colorectal cancer. Preliminary report on the prospective value of a combined screening method for occult rectal bleeding.

The authors have developed a specific, sensitive, simple and economic method for the detection of occult colorectal bleeding. The new technique consists of the traditional guaiac type reaction and an immunochemical test which as a second-phase test using dried filter paper discs serves to eliminate or reduce the false-positive reactions, decreasing the necessity of further invasive diagnostic measures. They report on their experience obtained with the screening of a rural population of 3,346 persons; a positive colour reaction was observed in 546 individuals (16.3%) who were not on diet. In the second-phase immunochemical examination, however, this number decreased to 54 (1.6%). In this group of patients, who did have blood in their stools, 5 colorectal carcinomas (9.25%), each in the early Duke stage A, could be detected. The overall detection rate of carcinoma, polyp and colitis ulcerosa, likewise a precancerous state, was 40.73%. The results obtained so far suggest that this combined screening method represents an easier, cheaper and a more rapid diagnostic method for the detection of early colorectal carcinomas and precancerous states compared to the conventional ones. In mass screening the treatment and transportation of the test specimens are simple and hygienic.

Aged↗
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

Vinblastine, cisplatin and bleomycin treatment of advanced nonseminomatous testicular tumors.

Between December 1979 and July 1986, 190 patients with nonseminomatous germ-cell testicular tumors were treated according to the modified Einhorn scheme. The response rate was 67.89%. The most favorable results were found in the embryonal histologic type (RR = 76.9%), in the biological marker (AFP, HCG) negative (RR = 97.43%) and in the minimal pulmonary extent group (RR = 94.12%).

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↗