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Biomedical subjects

S Seeber

Publications and source records attributed to S Seeber.

At least 235 records · Page 13Linked to original sources
PubMed1984

The tumor-inhibiting effect of isomeric dichloro(diphenylethylenediamine)platinum(II) complexes.

Ring unsubstituted dichloro(diphenylethylenediamine)platinum(II) complexes show a dependence of their antitumor activity on the configuration and position of phenyl rings in ethylenediamine ligand. Dichloro(1,1-diphenylethylenediamine)platinum(II) (1d) and meso-dichloro(1,2-diphenylethylenediamine)-platinum(II) (meso-2d) have a weaker effect on the human breast-cancer cell line MDA-MB 231 and on rat leukemia L 5222 than (+/-)-dichloro(1,2-diphenylethylenediamine)platinum(II)((+)-2d) and its enantiomers (+)-2d and (-)-2d which cause marked and comparable inhibition of both tumors; (+/-)-2d is also active on ADJ/PC 6 plasmacytoma of the mouse and on cisplatin-, daunomycin-, and cisplatin/daunomycin-resistant Ehrlich ascites tumors of the mouse. The differences in activity of the diastereomers (+/-)-2d and meso-2d, for which distinct influences on the DNA secondary structure can be demonstrated CD spectroscopically may be explained by a steric hindrance of the drug-DNA interaction.

Animals↗
PubMed1984

4'-Epi-Doxorubicin -- a clinical phase-II trial in solid tumors.

4'-Epi-doxorubicin is a new anthracycline analog with reduced cardiac toxicity in animal studies. A phase-II study was performed in 17 patients predominantly with non-small-cell lung cancer. All suffered from recurrent or advanced tumors and 7 of 16 evaluable patients had been pretreated with an alternative chemotherapy. 4'-Epi-doxorubicin was applied at a dose of 75 mg/m2 every 3-4 weeks. The median total dose was 280 mg (range: 130-250 mg). Only one patient with epidermoid lung cancer (overall response rate: 6%) showed a minor response and stable disease was observed in six other patients with bronchogenic carcinoma. Myelosuppression was rare and moderate: leukocytopenia of less than 2,000/mm3 occurred in 25% of patients and thrombocytopenia of less than 100,000/mm3 in 8% of patients. The frequency of alopecia and gastrointestinal side effects was 88% and 80%, respectively. Persistent electrocardiographic alterations were recorded in 2 of 14 (14%) patients. One of four patients revealed a marked reduction of left ventricular ejection fraction in radionuclide cardiography. It is concluded that 4'-epi-doxorubicin is not superior to adriamycin in this low-prospect treatment area, but studies with increased doses appear necessary in adriamycin-sensitive tumors because of recent reports from phase-III trials showing reduced cardiac and gastrointestinal toxicity with 4'-epi-doxorubicin in comparison with adriamycin.

Adult↗
PubMed1984

Phase II evaluation of fractionated low and single high dose cisplatin in various tumors.

Seventy-three evaluable patients with advanced measurable solid tumors were given cisdichlorodiammineplatinum (II) (DDP) at a dose of 20 mg/M2 IV for 1-5 days every 3 weeks, and 19 patients who failed on this low dose DDP protocol received a single high dose of 100 mg/M2 IV once every 3 weeks. Forty-six patients had received prior chemotherapy, and 29 patients were untreated. Results included four complete responses (5.5%) in malignant melanoma, spindle-cell sarcoma, adrenal carcinoma, and bladder carcinoma lasting 2 to 4 months. In 21 patients (28.8%), partial responses were achieved. Twenty-two patients (30.1%) showed stable disease and 26 (35.6%) had tumor progression. A response rate of 25% (4/16 patients) was found for malignant melanoma, 45.5% (5/11) for nonsmall-cell lung cancer, and 35.3% (6/17) for sarcomas of various types. One patient with teratocarcinoma, who relapsed on low-dose DDP, had another partial remission for 4 months after high-dose therapy. Toxicity was most commonly seen with gastrointestinal side effects and myelosuppression. Cumulative nephrotoxicity was prevented by prehydration and/or treatment with furosemide or mannitol.

Adult↗
PubMed1984

Experimental basis and clinical experience with non-cross-resistant combinations in solid tumours.

Experimental studies on anticancer drug resistance have shown that cisplatin and alkylating agents have a very low level of cross resistance towards heterocyclic agents such as anthracyclines, podophyllotoxins and vinca alkaloids. Based on this and on the model of Goldie and Coldman protocols using sequentially alternating non-cross-resistant combinations were given in testicular cancer, sarcomas and small cell bronchogenic carcinomas. Preliminary clinical results are presented here.

Animals↗
PubMed1984

Treatment of recurrent small cell lung carcinoma with vindesine and cisplatin.

Thirty-two males with recurrent small cell lung cancer after previous remission were treated with vindesine (3-4 mg/m2) plus cisplatin (60-100 mg/m2). Six patients (19%) responded to this therapy with two complete (CR) and four partial remissions. Minor responses were seen in another ten patients (32%). In patients with CR survival from start of treatment lasted 61 and 38 weeks; in patients who did not achieve CR median survival was 12 weeks. Nausea and vomiting were the predominant side effects, while only mild to moderate myelosuppression was noted. The vindesine and cisplatin regimen demonstrated significant activity against heavily pretreated small cell lung cancer, although chemotherapeutic response was poor in regions of prior irradiation.

Adult↗
PubMed1983

Phase II trial of aclacinomycin A in acute leukemia and various solid tumors.

Aclacinomycin A (ACM) is a new anthracycline antibiotic with a reduced cardiac toxicity in animal models. A phase II study was performed in a total of 25 patients, 23 of whom are evaluable for response. All suffered from recurrent and advanced tumors. Pretreatment consisted of at least four different chemotherapeutic agents (range: 4-9). Lung cancer patients (3/9) were irradiated to the mediastinum. Eighteen patients were pretreated with doxo- or daunomycin. The dose for solid tumors was 2-3 mg/kg given on 3 consecutive days every 3 weeks. Leukemia patients received a daily dose of 20 mg/m2, and standard response criteria were used. Marked reductions of leukocyte counts were achieved in leukemia patients. The overall response rate was about 15% in solid tumors, but major objective responses (CR + PR) have not been observed. Myelosuppression was commonly moderate in solid tumor patients, nausea and vomiting were rare, and alopecia was not induced. Cumulative cardiotoxicity was not evaluated in this trial. Treatment with ACM requires further investigation in acute leukemias and solid tumors, not pretreated with anthracycline antibiotics.

Aclarubicin↗
PubMed1983

Efficacy of ifosfamide in refractory malignant diseases and uroprotection by mesna: results of a clinical phase II-study with 151 patients.

In a clinical phase II study 151 patients with refractory malignant diseases were treated with ifosfamide (60 mg/kg/day i.v. days 1-5, q 21-28 days). Altogether, 490 courses of treatment were given, 92 with conventional prophylactic measures (continuous infusion of 3-4 litre physiological saline plus alkalinization of the urine) and 398 with mesna prophylaxis (12 mg/kg i.v., 0, 4 and 8 h after administration of ifosfamide). The overall response rate (min. 25% tumor reduction) was 67/151 (44%) including four complete remissions in a fairly unfavourable patient group with testicular teratoma (39/87), soft tissue sarcoma (10/16), malignant melanoma (2/7), osteogenic sarcoma (3/6), Ewing's sarcoma (2/6), lymphoma and acute leukemia (5/7) or other histologies (6/22). The response rate in patients pretreated by cyclophosphamide containing regimen was 7/19 (36%) including one complete remission and one partial remission. Mesna was highly effective in reducing the frequency of hemorrhagic cystitis from 25/92 (27%) to 16/398 (4%) ifosfamide courses. The antitumor activity of ifosfamide in testicular cancer was not reduced by mesna. In conclusion, ifosfamide with the potent uroprotector mesna appears to compare favourably with the most active agents in the treatment of malignant diseases.

Cyclophosphamide↗
PubMed1983

Ifosfamide in combination chemotherapy for sarcomas and testicular carcinomas.

The efficacy of ifosfamide combination chemotherapy was studied in 164 patients, 94 with advanced testicular carcinoma and 70 with metastatic sarcoma. Ifosfamide was given at 40-60 mg/kg/day i.v. on five consecutive days every 3-4 weeks together with mesna prophylaxis with 8 mg/kg i.v. being used at 0, 4 and 8 h after ifosfamide administration. Of 70 sarcoma patients 57 were evaluable for response, of whom 49 had received prior chemotherapy. The overall response rate was 46% (26/57) including 3 complete (CR) and 14 partial remissions (PR). Ninety-four patients with germ cell tumours of the testis were treated. Of 16 seminoma patients 15 achieved CR or PR. Seventy-eight patients with nonseminomatous testicular cancer who had received previous chemotherapy were either treated with ifosfamide/etoposide (n = 63, remission rate: 30%) or ifosfamide/cisplatin (n = 15, CR + PR: 33%). These results indicate that ifosfamide alone or in combination is active in sarcomas, seminomas and teratomas and that further studies are warranted employing the drug in first-line regimens.

Adolescent↗
PubMed1983

Treatment of refractory malignant lymphomas with ifosfamide/etoposide combination chemotherapy.

Twenty patients with malignant lymphomas refractory to prior combination chemotherapy were treated with ifosfamide (40 mg/kg/day i.v. days 1-5) and etoposide (120 mg/m2/day i.v., days 1, 3, 5). Altogether, 56 courses of treatment were given with prophylaxis of urinary side effects by mesna (8 mg/kg i.v. 0, 4, 8 hours after ifosfamide). The overall response rate (min. 25% tumor reduction) was 14/20 (70%) including 5/8 partial remissions in patients with non-Hodgkin's lymphoma and 2/12 partial remissions in patients with Hodgkin's disease. The lower total response rate of 7/12 in patients with Hodgkin's disease in comparison to 7/8 in patients with non-Hodgkin's lymphoma may be related to the different sensitivity of both diseases or to differences in the extent and duration of prior chemotherapy. As combination chemotherapy with ifosfamide/etoposide proved to be effective in refractory malignant lymphomas this combination may be included in combination chemotherapy programs for the salvage therapy or the initial treatment of malignant lymphomas with the alternation of non-cross-resistant chemotherapy combinations.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1983

[Sequentially alternating chemotherapy of non-seminomatous testicular tumors with adriamycin/cisplatin and bleomycin/vinblastine. Therapeutic success and failure with respect to histology and tumor stages].

The value of sequential alternating chemotherapy was analyzed retrospectively in 180 patients with disseminated, non-seminomatous testicular cancer. Response rates of adriamycin/cisplatin--(combination A) and bleomycin/vinblastine (combination B)--combination chemotherapy were evaluated separately with respect to tumor histology and tumor stages. Tumor response was achieved in 151 of 180 patients (84%) who were evaluable for adriamycin/cisplatin chemotherapy. Out of those, 91 of 117 patients (78%) pretreated with combination B and 60 of 63 patients (95%) without prior chemotherapy responded. Irrespective of pretreatment tumor response was observed in 131 of 157 patients (84%) evaluable for treatment with bleomycin/vinblastine. Resistance to combination A was 2.5 fold higher in embryonal carcinomas (class II of Dixon and Moore) than in choriocarcinomas (class V). Bleomycin/vinblastine-therapy failed more frequently in choriocarcinomas as compared to other histological categories (22% vs. 14%). This report also includes an analysis of treatment failures in different tumor stages. Both regimens were more frequently ineffective in tumor stages with a large tumor burden (stages II C and IV D). Patterns of cross-resistance were evaluated for both regimens. Response to adriamycin/cisplatin occurred in 18/26 patients (69%), when combination B had failed, and response to bleomycin/vinblastine was achieved in 14/24 patients (58%) when adriamycin/cisplatin had failed. In patients not responding to either regimen the treatment failure was already recognized after the first chemotherapeutic course in 93% of these cases.

Antineoplastic Agents↗
PubMed1982

[Short-term induction and cyclic maintenance therapy in inoperable small cell bronchial cancer].

Since July 1978 one hundred and three consecutive patients with unresectable small cell bronchogenic carcinoma were treated with a combination of doxorubicin, cyclophosphamide and vincristine (ACO). In limited disease patients (64) the second chemotherapy course was followed by prophylactic cranial irradiation, the fourth by irradiation towards primary disease sites. Complete responders were randomised to either receive etoposide or no further maintenance therapy. Objective responses were reached in 88/100 evaluable patients, with 72% of complete remissions in limited-stage disease and 33% in extensive disease, respectively. The actuarial median survival time for limited disease patients was 15.8 months compared to 9.3 months in extensive disease (p less than 0.005). 29 of the 100 patients remain still alive, 4 for more than 24 months without disease recurrence. The survival advantage of patients reaching complete remissions relative to those who did not is highly significant (p less than 0.001). Acute gastrointestinal and hematological side effects were common, with possibly three drug-related deaths from infections during transient granulocytopenia (mean nadir: 600-900 cells/mm3). The present induction regimen using only four courses of chemotherapy produces high complete remission rates on roentgenography and bronchoscopy and improved survival in the majority of patients. Thus far any effectiveness of etoposide-maintenance therapy following ACO could not be substantiated.

Adult↗
PubMed1982

[Progress in the therapy of testicular teratoid tumors].

Based on combination chemotherapy with vinblastine, bleomycin, cisplatin, ifosfamide, etoposide and adriamycin--these appear to be the most active agents--complete remissions between 60 and 70% of all patients with disseminated testicular teratomas appear realistic. Extent of disease, distribution and localization of metastases, patterns of specific markers such as alpha fetoprotein and beta-HCG, and the general condition of the patient at initiation of therapy determine the final prognosis. It appears most important that induction chemotherapy needs to be as intensive as possible: individualized doses and short intervals should be used initially despite some toxicity associated with this approach. In regional disease, four to six courses of adjuvant chemotherapy after lymphadenectomy have yielded cure rates as high as 95% (Stage II A) and 70% (Stage II B), respectively.

Antineoplastic Agents↗