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Biomedical subjects

C G Schmidt

Publications and source records attributed to C G Schmidt.

At least 73 records · Page 4Linked to original sources

Interferon alfa-2b in the treatment of chronic myelogenous leukemia.

Thirty-six patients with Philadelphia chromosome-positive CML were treated with interferon alfa-2b for at least 3 months. Thirty-two of the patients had chronic phase disease and four had acute phase disease, one in blast crisis. Patients initially received a daily dose of 4 megaunits/m2 administered subcutaneously; outpatient self administration followed at a dosage decreased in accordance with serially determined blood cell counts. Treatment was continued for 0.5 to 15 months, with a median duration of 7 months. No complete remission was achieved, but hematologic remission occurred in 21 (58%) patients, with partial hematologic remission in an additional 12 (33%). All four patients with acute phase disease failed to respond. Adverse reactions were only significant during the first days of treatment and did not interfere with self administration of the drug. Interferon alfa-2b may prove to be an important alternative therapeutic modality in chronic phase CML.

Adolescent↗

[Therapy of malignant systemic diseases: hemoblastoses and malignant lymphomas].

Recent progress in the treatment of acute leukemias in adults includes combination chemotherapy (TAD) and the use of high-dose antimetabolites (methotrexate plus citrovorum rescue or high-dose cytosine-arabinoside). The role of post-induction chemotherapy is still controversial especially with regard to the maintenance chemotherapy. The German AML (acute myeloid leukemia) Cooperative Group started a cooperative multi-center comparative trial to evaluate the validity of maintenance chemotherapy in patients with AML. A complete remission rate of 61% was achieved. The median time to complete remission was 33 days, and a complete remission was obtained in 68% of responders after only 1 course of therapy. Patients in complete remission were eligible for randomization for TAD consolidation with or without monthly maintenance chemotherapy. The up-dated life-table analysis revealed a predicted rate of continuous complete remission at 2 1/2 years of 30% for the maintenance and 17% for the non-maintenance group of patients (p = 0.003). On the basis of these results post-induction myelosuppressive chemotherapy appears to be substantial for achieving long-term remissions in AML. In addition, consolidation chemotherapy together with monthly maintenance seems to be superior to consolidation in prolonging the remission duration. In adult ALL/AUL (acute lymphatic/undifferentiated leukemia) complete remission rates amount to 60-85% and remission durations of 9-25 months have been reported.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

[Therapy of primary resistant or recurrent small cell bronchial carcinoma with vindesine and ifosfamide].

A combination of vindesine (3 mg/m2, day 1) and ifosfamide (60 mg/kg, days 1-5 + Mesna) was administered every three weeks to 11 patients with primary resistant and 23 with recurrent small-cell bronchial carcinoma. All patients had been pre-treated with chemotherapy, 16 in addition with radiotherapy. At the onset of the vindesine-ifosfamide treatment the cancer was in a localized regional stage in ten patients, while in 24 it was in a more widely spread stage. In 29 patients whose treatment results could be evaluated the remission rate was 38%, with two complete and nine partial remissions. In a further eight patients the cancer was arrested. The patients with complete remission (for 46 and 53 weeks, respectively), those with partial remission (median of 39 weeks) and those with stationary disease (median of 31 weeks) survived significantly longer than those with progressing disease (13 weeks). There was no correlation between treatment result and pre-treatment. On recurrence after complete remission or in the localized regional stage the remission rate was 70% and 60%, respectively, and the survival time was extended in 90% of cases. In addition to nausea, alopecia and myelosuppression, side-effects included vomiting, reversible CNS symptoms, polyneuropathy and urotoxicity. On the basis of acceptable toxicity, combined vindesine and ifosfamide constitute an effective treatment of otherwise treatment-refractory cases of small-cell bronchial carcinoma.

Antineoplastic Combined Chemotherapy Protocols↗

[alpha 2-interferon: preliminary treatment results in chronic myeloid leukemia].

Interferon (IFN-alpha 2 B) was administered to 21 patients with chronic myeloid leukaemia (CML), at an initial dose of 4 X 10(6) IU/m2 daily subcutaneously, adapted to changes in leukocyte count in the course of treatment. Of 16 patients that could be fully evaluated (12 males, 4 females; aged 21-64 years), 15 were in the chronic phase, one had a blast crisis. "Haematological remission" was achieved in nine of the 16 patients, while in the remainder, with one exception, transitory reduction in leukocyte count was obtained. With pretreatment counts of 18-151 X 10(9)/l, normalization to 2.7-6.9 X 10(9)/l was achieved in 13 patients after 3-40 weeks. In parallel to these effects there was a decrease in platelet count (before treatment 86-1550 X 10(9)/l to 30-279 X 10(9)/l after an average of six weeks) and in lactate dehydrogenase (initially 220-958 U/l to 87-232 U/l after 3-33 weeks). A reduction in Philadelphia chromosome-positive metaphases by as much as 50% was observed in four of eight patients. Administration of IFN-alpha 2 B achieved a relatively rapid cell reduction in the chronic phase of CML. The long-term effect on the course of the disease and the place of IFN in the overall concept of CML treatment remains unanswered.

Adult↗

Crossover comparison of the antiemetic efficacy of nabilone and alizapride in patients with nonseminomatous testicular cancer receiving cisplatin therapy.

Twenty nonseminomatous testicular cancer patients not pretreated with emetogenic chemotherapy were included in a crossover study of antiemetic therapy. Patients were randomly assigned to receive either nabilone (2 X 2 mg/day) or alizapride (3 X 150 mg/day) prior to beginning low-dose cisplatin chemotherapy. Patients on nabilone had significantly fewer episodes of emesis than those on alizapride (medians, 1.1 vs 2.9; p less than 0.01). Nabilone was superior to alizapride in giving complete relief from nausea (medians, 65% vs 30%; p less than 0.01), and was more effective in shortening the duration of nausea (medians, 1.3 h vs 5.1 h; p less than 0.01); however, it caused more adverse effects. It is concluded that nabilone has greater antiemetic activity than alizapride in young patients receiving low-dose cisplatin chemotherapy. Nabilone dosage should be reduced to decrease the incidence and degree of adverse reactions while leaving the definite antiemetic activity unchanged.

Administration, Oral↗

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↗

Transplantation of bone marrow with constitutional chromosomal anomalies. Cytogenetic studies and clinical implications.

We report on two cases of transplantation of bone marrow with constitutional chromosomal anomalies. A female patient with acute myelocytic leukemia (FAB, M 3) in first complete remission received a bone marrow graft from her sister with the karyotype 47 XXX (triple-X-syndrome). A male patient with Ph-positive CML and a constitutional Robertsonian t(14; 15) received HLA and MLC loci compatible bone marrow from his sister who was also a carrier of the Robertsonian t(14; 15). Our findings indicate that transplantation of marrow from donors with balanced chromosomal translocation is possible, although no conclusion can be made regarding long term results as both recipients died early from infectious complications.

Adult↗

Tumor biology and oncology.

The role of surgery in the management of human neoplasias is constantly undergoing reevaluation. Less surgical radicality reduces mutilating side-effects without a decrease in long-term survival if adjuvant chemotherapy is given. On the other hand, the surgical excision of isolated metastases helps to maintain curative intent even in the presence of residual disease after chemotherapy. Many experimental and clinical observations point to a predilection of circulating tumor cells for certain organs. Thus, the metastatic process is not simply a series of random events but rather governed by anatomical determinants such as venous and lymphatic drainage of the primary tumor and also by the intrinsic metastatic potential of the tumor cells themselves. The complex biology of metastasis is discussed with special reference to the surgical removal of isolated metastases.

Humans↗

Bone marrow transplantation in severe aplastic anemia and acute or chronic leukemia.

In Essen 121 bone marrow transplantations were carried out. The indications were severe aplastic anemia (n = 18), acute leukemia in relapse (n = 20), acute leukemia in remission (n = 46) or chronic myeloid leukemia (n = 37). The conditioning regimen consisted of cyclophosphamide or the combination of cyclophosphamide and total body irradiation. All patients were treated under strict gnotobiotic care. To mitigate the risk of CMV infections intravenous CMV-hyperimmunoglobulin and CMV-negative blood products have been applied routinely since two years. MTX was used as prophylaxis against GVH-disease. In case of severe aplastic anemia 13 patients (72%) are still alive with a median observation time of 24 months. In the prognostically unfavourable group of acute leukemia in relapse only one patient showed long term survival. In this patient leukemic relapse occurred six years after transplantation. The survival rate of AML patients grafted during the first remission is 55% (15/27) with a median observation time of 40 months. For patients grafted in first or consecutive remission of ALL the survival rate is 42% (5/12) with a maximal observation time of 29 months. Out of 37 patients grafted because of CML, eight were in an advanced stage of the disease. 13 patients are still alive, the maximal observation time is 37 months. The overall incidence of GVHD in patients at risk was 28% in aplastic anemia, 26% in AML, 9% in ALL and 63% in CML. In aplastic anemia no patient developed an interstitial pneumonia. In leukemia the risk of fatal interstitial pneumonia was 34%.

Acute Disease↗

Aminoglutethimide without hydrocortisone in the treatment of postmenopausal patients with advanced breast cancer.

In a phase II study, 38 evaluable patients with advanced progressive breast cancer were treated with 4 X 250 mg of aminoglutethimide per day without hydrocortisone supplementation. Partial remissions were observed in five patients (13%), with a median duration of 9 months (range, 7-15), and stable disease was observed in 17 patients (45%), with a median duration of 4 months (range, 2-11). The recorded side effects (CNS, cutaneous, gastrointestinal) were tolerable and transient and required drug discontinuation in only four patients. Serial determinations of serum hormone levels during aminoglutethimide treatment revealed a significant decrease in estradiol and an increase in gonadotropins, testosterone, and progesterone. No patients had adrenal insufficiency. In contrast, despite prolonged aminoglutethimide treatment and persisting hypoestrogenemia, both cortisol levels and adrenal responses to ACTH remained unaltered. It is concluded that aminoglutethimide alone is effective in the treatment of postmenopausal patients with breast cancer. Moreover, based on the present findings, a prospective randomized study is warranted to show that hydrocortisone supplementation appears to not be mandatory, either for increase in efficacy or for decrease in side effects of the treatment.

Adult↗

Enhancement of semustine-induced cytotoxicity by chlorpromazine and caffeine in a human melanoma xenograft.

Chlorpromazine (CPZ) and caffeine (CFN) enhance the cytotoxicity of nitrosoureas in conventional murine tumor systems, but this effect was not confirmed in a randomized clinical trial which compared the action of semustine (MeCCNU) against the combination of MeCCNU, CPZ, and CFN. Since differences in repair systems are known to exist between cells of human or murine origin, we have employed a human melanoma xenograft system to quantify the drug interaction. The enhancement in human melanoma cells was similar to that observed with conventional murine tumor systems. Alkaline elution studies and determination of radioactivity from labeled MeCCNU pointed to increased drug retention and fixation of DNA damage as the mechanism of enhancement. Although toxicity studies were limited to murine tissues, there was evidence of increased toxicity, especially if MeCCNU was combined with both CPZ and CFN. Thus, a true therapeutic synergism may not be present for the combination. Some explanations for the failure to detect such drug interaction in clinical trials and the relevance of advanced preclinical tumor systems are discussed.

Animals↗