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Biomedical subjects

C G Schmidt

Publications and source records attributed to C G Schmidt.

At least 109 records · Page 6Linked to original sources
PubMed1984

Comparative effects of ASTA Z 7557 (INN mafosfamide) and cyclophosphamide on hematopoiesis in mice.

Acute effects of ASTA Z 7557 and Cyclophosphamide (Cy) on pluripotential (CFU-S), granulocytic (CFU-C), early erythroid (BFU-E) and late erythroid (CFU-E) progenitor cells in the bone marrow, as well as on RBC and WBC, were compared in F1 (CBA X C 57 BL) female mice. Dose-survival curves of both agents for CFU-S and CFU-C were found to be exponential, indicating that the effects of the drugs have no cell cycle dependency. At equimolar doses, marrow CFU-S and CFU-C contents appeared to decrease more rapidly with increasing doses of ASTA Z 7557 than with those of Cy. After a single dose of 200 mg/kg of each drug ( = 50% LD10), there was greater initial suppression of CFU-S, CFU-C, BFU-E and CFU-E in the Cy-treated animals than in ASTA Z 7557-treated mice. In both groups, however, the WBC had their nadir on Day 3 after treatment, followed by a return to normal by Day 8. In ASTA Z 7557-treated animals, the recovery of CFU-S, CFU-C and BFU-E was also completed by Day 8 after treatment. In Cy-treated mice, however, complete recovery of these cells was achieved on Day 15. Results indicate quantitative rather than qualitative differences between the marrow toxicities of ASTA Z 7557 and Cy in mice. Quantitative differences could be due to different pharmacokinetic properties of the agents, since Cy is excreted in partially unmetabolized form, and it might be that this inactive part of the agent grew increasing drug doses.

Animals↗
PubMed1984

Clonal evolution with isodicentric Ph1 chromosome in Ph1-positive CML: karyotypic conversion after bone marrow transplantation.

Clonal chromosomal evolution was observed in a 16-year-old boy suffering from Ph1-positive CML. An isodicentric Ph1 chromosome appeared 20 weeks after the initial diagnosis. At that time an allogeneic bone marrow transplantation was performed. Thereafter, during an observation period of more than 13 months, chromosome analyses showed neither the Ph1 chromosome nor the abnormal isodicentric variant. Close cytogenetic monitoring is suggested to reveal early unfavorable prognostic signs of the onset of blast crisis before it becomes evident in the bone marrow morphology.

Adolescent↗
PubMed1984

Laminar air flow versus barrier nursing in marrow transplant recipients.

Forty-eight patients with acute leukaemia in relapse (n = 14), acute leukaemia in complete remission (n = 19), chronic myeloid leukaemia (n = 8) or severe aplastic anaemia (n = 7) received a marrow transplant. The first 26 patients were nursed in laminar-air-flow plastic isolators while the next 22 patients were treated in barrier nursing rooms. Gnotobiotic parameters and morbidity in the 2 groups are compared. Good decontamination of the gastro-intestinal tract was obtained using either of the 2 isolation techniques. The incidence of bacterial and mycotic infections, as well as the supportive care required by the patients was almost equal in both groups. Our results also suggest that the incidence of graft versus host disease may decrease with efficient decontamination of the patients.

Anemia, Aplastic↗
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

Sister chromatid exchange in normal and Ph1-positive leukemic cells after mitomycin-C treatment in vitro.

The sister chromatid exchange (SCE) frequency was investigated in normal bone marrow and Ph1-positive cells of chronic myelocytic leukemia (CML) patients with and without mitomycin-C (MMC) treatment in vitro. Even though the spontaneous SCE frequency was found to be significantly lower in CML cells, the absolute SCE values after MMC treatment did not differ between leukemic and normal cells, and this seems to indicate an equilization of SCE rates. However, the fact that leukemic cells with lower spontaneous SCE rates need a further increase of SCE to reach values equal to those of normal cells might indicate a somewhat higher susceptibility of leukemic cells to DNA damage by MMC. This interpretation appears to be confirmed by the fact that the inhibition of cellular proliferation at higher MMC doses considerably reduced the number of leukemic cells that was able to divide twice during a given culture time.

Adolescent↗
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

Continuous infusion versus intermittent bolus injection of bleomycin in a human embryonal testicular cancer xenograft.

In vivo experiments with bleomycin in conventional murine tumor systems indicate a superiority of continuous-infusion schedules over daily intermittent bolus injections. This schedule of administration has been incorporated into many clinical trials, especially in testicular cancer, on the basis of in vitro and in vivo experiments as well as favorable comparisons with historical controls. Since mechanisms linked to a superiority of continuous-infusion schedules may not be operative in every individual tumor line, we have compared both schedules of administration in a human testicular cancer xenograft. We found no significant difference with respect to antineoplastic response.

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↗
PubMed1984

[Polychemotherapy in inoperable bronchial carcinoma].

The course of the bronchial carcinoma and the therapeutic chances are influenced by the histologic tumor type which determines the respective biologic behavior. The most important clinical finding is the differentiation between small-cell and non-small-cell bronchial carcinomas. Small-cell bronchial carcinomas are characterized by a rapid duplication of the tumor volume, a high rate of cell divisions and an early hematogenic and lymphogenic dissemination. They have therefore a good response to antiproliferative chemotherapy. In almost 80% of patients bronchial carcinomas with limited disease, a complete remission and a markedly prolonged median survival time can be achieved by combined cytostatic chemotherapy, e.g. the therapy regimens ACO I and ACO II. As yet, the problem of local and remote recurrences is not solved. The unfavorable prognosis of the primarily inoperable small-cell bronchial carcinoma can be improved by chemotherapy. On the other hand, the high remission rate is diminished by later incurable recurrences. A pretherapeutic differentiation of limited and extended disease is necessary. The necessity and conditions of an additional radiotherapy have to be determined later on by means of prospectively randomized therapy studies. As opposed to the small-cell bronchial carcinoma, the non-small-cell bronchial carcinoma shows a markedly lower response to chemotherapy. Adenocarcinomas are comparatively refractory to chemotherapy, but squamous cell carcinomas respond now a little better to chemotherapy.

Adenocarcinoma↗
PubMed1983

[Testicular tumors--a breakthrough?].

The prognosis of nonseminomatous germ cell testis tumors has been significantly improved during the past two decades due to progress in cytostatic treatment. General trends and our own long term experience with sequential combination chemotherapy (velbane/bleomycin; adriamycin/cisplatin; ifosfamide/etoposide) in testicular cancer are presented. In disseminated stages survival was closely related to the initial concentration of human chorionic gonadotropin (HCG) and tumor burden (two year survival: more than 80% in patients with minimal pulmonary disease, 40-50% in patients with massive pulmonary disease, and less than 30% in patients with pulmonary metastases and massive retroperitoneal disease). New diagnostic and therapeutic methods to increase survival rates further in nonseminomatous testicular cancer are discussed.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1983

Therapeutic evaluation of five nitrosoureas in a human melanoma xenograft system.

The development of nitrosoureas has switched from more lipophilic derivatives to congeners with higher water-solubility, since this property was presumably associated with a decrease in myelosuppression. We have compared the therapeutic efficacy of clinically well-known lipophilic nitrosoureas BCNU, CCNU, and MeCCNU with the recently introduced water-soluble nitrosoureas chlorozotocin (CZT) and hydroxyethyl-CNU (HeCNU), using a human melanoma xenograft system. There were considerable differences in tumor-inhibitory activity, with HeCNU ranking first and CZT last, and the rank order was similar for drug-induced lethality or bone marrow damage (in terms of reduced cellularity or macromolecular DNA damage). When the doses are expressed as percentages of the corresponding LD10/30 values, CZT ranks last and HeCNU low among conventional nitrosoureas. We conclude that water-solubility is not associated with reduced myelosuppression and that other guidelines will have to be adopted for rational development of nitrosoureas.

Animals↗
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

[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↗
PubMed1983

[Anaphylactic reaction in cyclophosphamide infusion].

A number of drugs used in cancer chemotherapy have produced hypersensitivity reactions. Generalized urticaria to cyclophosphamide has been reported previously in 5 cases. We have recently observed a 25-year-old patient with M. Hodgkin who developed an anaphylactic shock immediately following an intravenous infusion of cyclophosphamide. Total serum IgE was significantly elevated (1280 U/ml). Using the epicutan skin testing highly positive papulo-vesicular reaction to cyclophosphamide was observed.

Adult↗