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Biomedical subjects

S Seeber

Publications and source records attributed to S Seeber.

At least 217 records · Page 12Linked to original sources
PubMed1988

Phase I study of pirarubicin.

A Phase I trial of pirarubicin (4'-O-tetrahydropyranyl-doxorubicin) was undertaken to study its toxicity and to gain preliminary knowledge of its efficacy. The dose was escalated by increments of 10 from 30 to 70 mg/m2. Out of 20 patients, 19 were evaluable for toxicity and response to treatment. Hematologic toxicity was dose limiting and dose related. Other adverse effects included nausea and vomiting, hair loss, and stomatitis. No acute cardiotoxicity was encountered. In 2 patients with metastatic breast cancer who had not been pretreated with cytostatic agents, a partial remission was achieved lasting for 5 months. In 6 patients, tumor parameters did not change for a median of 3 months, and 11 patients suffered progressive disease.

Adult↗
PubMed1988

Influence of ring substituents on the antitumor effect of dichloro(1,2-diphenylethylenediamine)platinum(II) complexes.

Diastereomeric para-substituted dichloro(1,2-diphenylethylenediamine)platinum(II) complexes were synthesized and tested for their antitumor activity on the human MDA-MB 231 breast cancer cell line and the P 388 leukemia of the mouse. An interaction with the DNA was demonstrated by UV difference spectroscopy. The D,L configurated, 4-fluoro-substituted complex was the most active.

Animals↗
PubMed1988

[Sequential treatment of progressive metastatic colorectal cancer with 5-fluorouracil/folinic acid, dipyramidole and mitomycin C].

A number of reports have described enhanced therapeutic activity of 5-fluorouracil (5-FU) when combined with high-dose folinic acid (dl-CF). In the present phase-II study 35 patients with colorectal cancer were entered into a first-line chemotherapeutic protocol consisting of dl-CF 200 mg/m2 i.v. push directly followed by 340 mg/m2 5-FU i.v. pushon - days 1-5. Thus far a response rate of 37.5% (12 PR) has been achieved, and minor responses or no change were registered in 43.7% (14 MR or NC), lowering the rate of primary therapeutic failures to 18.8%. Median time to progression was 6.2 months. Toxic side effects consisted mainly of diarrhea, nausea and mucositis. As second-line therapy 5-FU/dl-CF and dipyramidole p.o. were administered to 10 patients with resulting 4 NC. Mitomycin C was given to 9 patients as a third-line regimen with resulting 5 NC for 2-4 months.

Adult↗
PubMed1987

[Liposarcoma].

Explore the source record for details and available documents.

Female↗
PubMed1987

Positive correlation between decreased cellular uptake, NADPH-glutathione reductase activity and adriamycin resistance in Ehrlich ascites tumor lines.

From a wild type strain of Ehrlich ascites tumor (EATWT) sublines resistant to daunorubicin (EATDNM), etoposide (EATETO), and cisplatinum (EATCIS) have been developed in vivo. Increase in survival and cure rate caused by adriamycin (doxorubicin) have been determined in female NMRI mice which were inoculated i.p. with EAT cells. Adriamycin concentrations causing 50% inhibition of 3H-thymidine (ICT) and 3H-uridine incorporation (ICU) and intracellular adriamycin steady-state concentrations (SSC) were measured in vitro. Adriamycin resistance increased and SSC decreased in the following sequence: EATWT - EATCIS - EATDNM - EATETO. When ICT and ICU were corrected for intracellular adriamycin concentrations in consideration of the different SSC (ICTc, ICUc), ICTc and ICUc still varied up to the 3.2 fold in EATCIS, EATDNM and EATETO in comparison to EATWT. Thus, in addition to different SSC other factors must be responsible for adriamycin resistance. Therefore, enzymes which may play a role in the cytotoxicity related to adriamycin metabolism (NADPH-cytochrome P-450 reductase, NADPH-glutathione reductase, NADP-glucose-6-phosphate dehydrogenase, NADP-isocitrate dehydrogenase) were measured. In contrast to the other parameters determined, NADPH-glutathione reductase was significantly (p less than 0.01) increased up to the 3.2 fold parallel to adriamycin resistance as determined by increase in life span, cure rate, ICTc, and ICUc, respectively. It is concluded that high activities of NADPH-glutathione reductase may contribute to an increase in adriamycin resistance of malignant tumors.

Animals↗
PubMed1986

Enhancement of etoposide-induced cytotoxicity by cyclosporin A.

Following the clinical observation of enhanced antineoplastic action of etoposide in the presence of cyclosporin A (CyA), we investigated this drug interaction in several in vitro and in vivo tumor systems. Macromolecular DNA damage induced by etoposide at drug levels comparable to plasma AUC values achieved in patients was increased not only in leukemic peripheral blood cells from patients but also in mononuclear peripheral blood cells from a healthy donor. Intracellular retention of radioactivity from 3H-etoposide was increased by a factor of 1.5 at the most in the presence of CyA. The cytotoxicity of etoposide and adriamycin to L 1210 leukemic cells was clearly enhanced, whereas CyA had no effect on the action of cisplatin or ionizing irradiation. At CyA blood levels not exceeding 1.44 microgram/ml, increased tumor inhibition of etoposide was observed in a human embryonal cancer xenograft, but there was also higher lethality in normal mice. We conclude from our own data and from other recent findings that with respect to chemosensitization the effects of CyA resemble those of calcium channel blockers or anticalmodulin agents. In contrast to calcium channel blockers, however, adequate plasma levels of CyA can well be achieved in patients.

Animals↗
PubMed1986

Comparative activity of ifosfamide and cyclophosphamide.

Antitumor activity (increase in lifespan and cure) was greater for ifosfamide (IFO) in several experimental tumors, some of which were primarily resistant to cyclophosphamide (CYC). IFO has been shown to be active in anthracycline-resistant and in adriamycin/cisplatin-resistant sublines of an Ehrlich ascites tumor, as well as in tumor cells primarily resistant to CYC. The few comparative controlled clinical trials available suggest superior single-agent activity of IFO compared with CYC in soft tissue sarcoma and ovarian cancer. Combination chemotherapy with IFO has been effective in second-line treatment of sarcomas, malignant lymphomas, lung cancer, and testicular cancer, most of them pretreated with or refractory to CYC. Although it is difficult to obtain clinical proof that there is no cross-resistance between IFO and CYC, IFO has been shown to be active in multirefractory malignant lymphomas, in small cell lung cancer not responding to adriamycin, vincristine, and etoposide, and in soft tissue and bone sarcomas. Testicular cancer and pancreatic cancer are some of the tumors in which IFO activity is currently being evaluated and in which CYC has so far failed to show sufficient clinical activity. More comparative controlled clinical trials are needed in ovarian cancer, breast cancer, malignant lymphomas, sarcomas and cervical cancer, in which IFO has already shown sufficient single-agent activity. Due to its lower level of cross-resistance with a variety of heterocyclic products, but also with other alkylating agents, in addition to its use in induction chemotherapy, IFO is an important second-line agent in many clinical situations.

Animals↗
PubMed1985

[Chemotherapy of advanced lymphogranulomatosis. Results of MOPP/COPP treatment at the West German Tumor Center, Essen].

Between 1968 and 1979, a total of 271 patients with advanced Hodgkin's disease received as first systemic chemotherapy MOPP (mechlorethamine [nitrogen mustard], oncovin [vincristine], procarbazine and prednisone) or COPP (as above, but cyclophosphamide instead of nitrogen mustard). In 162 of the 271 patients (60%) full remission was achieved. Demonstration of systemic signs, bioptically confirmed bone-marrow infiltration and suboptimal cytostatic dosage correlated significantly with a lower full-remission rate. A significant trend towards a lower remission rate was demonstrated for stage IV disease, in patients with lymphocyte-poor or unclassified Hodgkin's disease and in those older than 30 years. A five-year recurrence-free period was achieved in 75.5% of patients: stage of the disease and bone-marrow infiltration had a clear influence on recurrence-free survival rate. The results show that 50% of patients with advanced Hodgkin's disease can be cured by chemotherapy.

Adult↗
PubMed1985

Chemotherapy of metastatic seminoma.

Response to chemotherapy and survival was retrospectively analyzed in 28 patients with bulky retroperitoneal and disseminated seminoma treated between 1977 and 1983. The median age was 41 years (range: 23-52). All patients had histological evidence of pure testicular seminoma, however, 14 patients revealed moderate increases of human beta-chorionic gonadotropin levels. Prior radiotherapy had been given to 9/28 (32%) patients. Treatment consisted of at least four courses of simultaneous or sequentially alternating therapy with cisplatin, vinblastine, bleomycin plus/minus adriamycin (PVB +/- A), administration of ifosfamide or combination therapy with ifosfamide/cisplatin (IFS/DDP) or ifosfamide/etoposide (IFS/ETP). Twenty-five of 28 patients (89%) achieved a complete (CR), and 3/28 patients a partial remission. Relapse occurred in 1/8 CR patients after adjuvant postchemotherapeutic irradiation, and in 1/11 patients without any further radiotherapy. So far, 23/28 patients (82%) are free of disease after a median follow-up of 28+ (14+----82+) months. Marked myelosuppression was observed in previously irradiated patients, mainly after PVB +/- A therapy. In two patients, transient nephrotoxicity developed after PVB and IFS/DDP, respectively. After PVB +/- A chemotherapy, three patients revealed polyneuropathy, paralytic subileus and bleomycin-induced pneumonitis, respectively. In conclusion, the present series suggests a high probability of continuous CR in even bulky retroperitoneal and widespread metastatic seminoma. So far, no definite conclusions can be made on the therapeutic superiority of one of the different chemotherapeutic regimens used. However, this preliminary experience suggests that the combination of ifosfamide and etoposide or cisplatin may prove less toxic than sequentially alternating or simultaneous PVB +/- A chemotherapy.

Adult↗
PubMed1985

[Principles of high-dose cytarabinoside treatment].

Ara-C can be regarded as an analogue of cytidine and of deoxycytidine. It is activated by a kinase system leading to Ara-CTP and inactivated by deaminases mainly to Ara-U. Resistance to Ara-C can develop by at least four mechanisms: decreased activation, increased inactivation, decreased half-life of intracellular Ara-CTP and decreased cellular incorporation. Following short-therm high-dose infusions, therapeutically significant concentrations in blood and cerebrospinal fluid can be achieved for 6-12 hrs. The concept of high dose Ara-C is thus based on solid biochemical and pharmacological data; its application in refractory leukemias and lymphomas and in leukemic meningeosis is, however, restricted by significant toxicity and by the reduced normal stem cell potential in these patients.

Acute Disease↗
PubMed1985

[High-dose cytarabine treatment in acute leukemias and leukemic meningiosis: clinical aspects and pharmacokinetics].

Clinical reports concerning the therapeutic effects of high dose Cytosine arabinoside (HD Ara-C) in meningeal leukemia are relatively rare. Pharmacokinetic studies, however, have indicated potentially effective concentrations of Ara-C in cerebrospinal fluid (CSF) during and after high-dose infusions of the drug given intravenously. In this report, the treatment results of HD Ara-C in 14 patients with refractory or relapsed acute leukemia are presented including those of 2 patients with meningeal leukemia. In these 2 patients as well as in 1 patient without central nervous system (CNS) leukemia, Ara-C and Ara-U concentrations in CSF and plasma were measured during a 6-day therapy with HD Ara-C (3 g/m2 q 12h 12 X). Ara-C and Ara-U levels were determined on Days 3 and 6 of therapy, each at the end of a 3-h i.v. infusion of the drug. In the 14 patients (8 with AML, 6 with ALL) treated, a total number of 17 treatment cycles were given for remission induction with doses of Ara-C ranging from 1-3 g/m2 q 12 h 6-12 X. A complete remission rate of 47% was achieved. The duration of remission ranged from 1 to 6 months. Of the 2 patients with CNS leukemia, 1 patient achieved complete remission both in CSF and in bone marrow, the other patient only in CSF. The mean concentration of Ara-C in CSF was 903 ng/ml with a ratio of 0.38 to that in plasma. Ara-C and Ara-U did not appear to accumulate in CSF or in plasma.(ABSTRACT TRUNCATED AT 250 WORDS)

Acute Disease↗
PubMed1984

Vindesine/cisplatin chemotherapy in relapsed or primarily resistant small-cell carcinoma of the lung.

Thirty-eight pretreated patients with primarily resistant [6] or relapsed [32] small-cell lung cancer were treated with a combination of vindesine (3-4 mg/m2) and cisplatin (60-100 mg/m2). Eight patients responded to this therapy with three (8%) complete and five (13%) partial remissions. Minor responses were noted in 12 (32%) additional patients. Chemotherapeutic response was rare in regions of prior irradiation. In the complete remission group survival from start of vindesine/cisplatin therapy lasted 61, 48 and 38 weeks, respectively. In the "less-than-complete-remission" group median survival was 12 weeks. Nausea and vomiting were the prominent side-effects, while only mild to moderate myelosuppression was noticed in most cases. The vindesine/cisplatin combination showed significant activity in heavily pretreated small-cell lung carcinoma. However, the remission rates remain low in this unfavourable condition, which might be due to pronounced chemotherapeutic resistance in previously irradiated areas.

Adult↗
PubMed1984

Predictive tests in cancer chemotherapy. A reappraisal.

The evolution of medical oncology so far owes much to the preclinical and clinical development of antineoplastic agents. Prognostic factors and empiric treatment strategies have guided the clinician in his choice of drugs. In the light of increasing ethical restrictions met with phase I-II clinical trials and major advances in propagating human tumor cells outside the donor patient, a reappraisal of predictive tests in cancer chemotherapy is warranted. Among 'short-term assays' only the determination of steroid-hormone receptor content in tumor tissues has gained clinical acceptance, whereas other methods still suffer from theoretical or practical shortcomings. Both the human tumor stem cell assay and the xenograft model have revealed unique patterns of sensitivity for each individual tumor line. While interindividual heterogeneity among tumors sharing a common site of origin justifies efforts to develop predictive tests, microheterogeneity among tumor samples from the same donor patient limits the potential of this approach. Predictive tests should be performed in conjunction with clinical trials to ensure optimal extraction of information. As additional prognostic factors, they should in the near future accelerate drug development and reduce the hazard of unnecessary drug toxicity without therapeutic benefit.

Animals↗