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Biomedical subjects

D K Hossfeld

Publications and source records attributed to D K Hossfeld.

At least 163 records · Page 9Linked to original sources
PubMed1991

[Multicenter prospective controlled study of therapy of chronic myeloid leukemia. Comparison of busulfan, hydroxyurea and interferon alpha (April 1990 status)].

In a multicenter study it is being determined, whether the use of hydroxyurea or of interferon alpha instead of busulfan prolongs the chronic phase of Philadelphia-positive CML. Additional goals are the examination, whether the types of disease evolution and the terminal phases differ between the treatment groups, and the prospective recognition of prognostic criteria for the duration of the chronic phase of CML. By September 5, 1990, 593 CML-patients had been randomized, 221 for busulfan, 228 for hydroxyurea and 144 for interferon alpha. The average age is about 51 years. By April 30, 1990, 106 patients had reached the end of the chronic phase, 126 had died. The median survival of Philadelphia-positive patients was 3.95 years, that of all patients 3.75 years. The median observation time of all patients was 1.34 years (mean 1.60 years). At present, no significant difference in survival is recognizable between the three treatment arms, although fewer adverse effects have been observed in the hydroxyurea arm.

Busulfan↗
PubMed1991

Carboplatin in small cell lung cancer.

Carboplatin is one of the most active agents in untreated small cell lung cancer (SCLC) (14% complete response [CR] and 61% CR + partial response [PR]). The combination carboplatin/etoposide/vincristine (CEV) (phase II trial) led to an overall remission rate of 84% in patients with limited disease, with 52% CR. The median survival time with this combination was 13 months in patients with limited disease and 9.5 months in those with extensive disease. The 30-month survival rates are 30% in limited disease and 10% in extensive disease with a plateau of the survival curve. This regimen is highly effective and exhibits low toxicity in SCLC. To evaluate the role of carboplatin in combination chemotherapy in patients with extensive SCLC, a phase III trial was performed. In this ongoing trial comparing CEV and etoposide/vincristine in SCLC patients with extensive disease, CR and overall response rates to date are higher in the CEV arm (CR 30% v 10%, CR + PR 90% v 75%), but as yet the differences are not statistically significant. In summary, chemotherapy regimens containing platinum compounds are among the most active in the treatment of SCLC. The use of the new compound carboplatin instead of cisplatin has led to similar or increased remission rates and is preferable because it has fewer side effects. Preliminary results from this ongoing, prospective, randomized phase III trial will be presented.

Adult↗
PubMed1990

Effects of verapamil on anthracycline-induced cardiomyopathy: preliminary results of a prospective multicenter trial.

Previous investigations in animals and one retrospective study in man suggest that verapamil can prevent anthracycline-induced cardiomyopathy. In the following study, patients with acute myeloid leukemia (AML) treated with double induction and consolidation chemotherapy (AML COOP study 1986, [3]) were randomized in a group with and without accompanying low-dose oral verapamil treatment. Since July 1986, 64 patients have been included. Thirty patients have been evaluated for pre- and posttreatment cardiological investigations. So far, no significant difference in cardiotoxicity has been observed either between the verapamil and nonverapamil group or between the two induction chemotherapy regimens (TAD/TAD - TAD/HAM).

Adolescent↗
PubMed1990

Pharmacokinetics and metabolism of iodo-doxorubicin and doxorubicin in humans.

The pharmacokinetics of doxorubicin (DOX), iodo-doxorubicin (I-DOX) and their metabolites in plasma has been examined in five patients each receiving 50 mg/m2 of both anthracyclines as a bolus injection. Terminal half-life, mean residence time (MRT), peak plasma concentration Cmax, and area under the curve (AUC) appeared smaller for I-DOX, whereas its plasma clearance (CLP) and volume of distribution at steady state (Vss) were larger than for DOX. The major metabolite of I-DOX was iodo-doxorubicinol (I-AOL) followed by doxorubicinol aglycone (AOLON). The AUC of I-AOL was 6-times larger than that of its counterpart AOL, which is the major metabolite of DOX. AOLON generated after I-DOX administration is a further important metabolite, as its AUC was 10-times larger than that of AOLON generated from DOX. The other aglycones, such as doxorubicin aglycone (AON) and the 7-deoxy-aglycones were only minor metabolites after either I-DOX or DOX injection. The ratio AUCI-AOL/AOL/AUCI-DOX/DOX was 27 in the case of I-DOX and 0.4 after DOX. The terminal half-lives of the cytostatic metabolites I-AOL and AOL were similar, although a longer MRT for AOL was calculated. Both metabolites had much longer MRTs than their parent drugs. The MRTs of the aglycones AOLON and AON were greater than those of the 7-deoxy-aglycones after both I-DOX and DOX. Approximately 6% DOX and less than 1% I-DOX were excreted by the kidneys during the initial 48 h. About 5% of I-DOX was excreted via the kidneys as I-AOL. Aglycones were not detected in significant amounts.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗
PubMed1990

A phase II study of intensive-dose epirubicin/verapamil as induction therapy followed by intensive-dose ifosfamide for advanced breast cancer.

Preliminary data of an ongoing phase II-study in metastatic breast cancer patients are presented. Patients with metastatic breast cancer entered the study after hormone therapy had failed; prior treatment with cyclophosphamide, methotrexate and 5-fluorouracil (CMF) was also allowed. The patients were treated with three cycles of 40 mg/m2 epirubicin i.v. on days 1-3 and 4 x 120 mg oral verapamil on days 0-3, given every 3-4 weeks. After three chemotherapy courses, ifosfamide was given as a short infusion of 3 g/m2 on days 1-3. Mesna (20% of the total ifosfamide dose) was given 0, 4 and 8 h after ifosfamide administration. Response was evaluated after three cycles of epirubicin/verapamil and after the last (third) cycle of ifosfamide. The side effects of this treatment were tolerable. The epirubicin/verapamil combination was no more toxic than epirubicin alone. Despite the high dose of verapamil, systolic blood pressure remained above 80 mm Hg, and patients never had a period of strict bed rest. Alopecia was almost complete after induction therapy with epirubicin/verapamil, and nausea and vomiting were absent or mild during epirubicin/verapamil chemotherapy and were easily controlled by antiemetics during ifosfamide treatment. Stomatitis and mucositis, the main toxic effects, could be ameliorated by intensive mouth-washing procedures. The haematological toxicity was greater after epirubicin/verapamil treatment than after ifosfamide therapy, but neither bleeding nor infections due to thrombocytopenia or leucopenia were observed.

Adult↗
PubMed1990

Phase II study of carboplatin in untreated, inoperable non-small-cell lung cancer.

A total of 51 previously untreated patients with non-small-cell lung cancer (NSCLC) were treated with 130 mg/m2 carboplatin given every 4 weeks as an i.v. infusion on days 1, 3, and 5. Ten patients achieved a partial response and five, a minor response. The overall response rate was 20% (95% confidence limits, 8%-32%). The median duration of response was 3 months and the median overall survival was 4.5 months. Leucopenia, thrombocytopenia and anemia of WHO grade 3 occurred in 4%-6% of patients and grade 3 nausea and vomiting was observed in 8% of our subjects. Grade 4 thrombocytopenia occurred in 3 (6%) patients. Apart from nausea and vomiting, nonhematologic toxicities above grade 2 were not observed. Further trials using carboplatin in NSCLC as a single agent or in combination with other chemotherapeutic agents or radiation are warranted.

Adult↗
PubMed1990

Results of chromosome studies and their relation to morphology, course, and prognosis in 120 patients with de novo myelodysplastic syndrome.

Cytogenetic studies were performed in 120 patients with de novo myelodysplastic syndrome (MDS) classified according to FAB criteria. Twenty-eight patients had refractory anemia (RA), 14 had refractory anemia with ring sideroblasts (RARS), 45 had refractory anemia with blast excess (RAEB), 19 had refractory anemia with blast excess in transformation (RAEB-t), and 14 had chronic myelomonocytic leukemia (CMMoL). Fifty patients (42%) had clonal chromosome anomalies at initial analysis. The most common cytogenetic anomalies were: 5q- (11 patients), trisomy 8 (nine patients), -7/7q- (6 patients), 12p- (five patients), followed by structural anomalies of chromosome 17 (four patients), and loss of Y chromosome (three patients). The prognostic value of chromosome anomalies was examined by comparison of the significance of single chromosome anomalies (34 patients) versus multiple cytogenetic changes (16 patients). Patients with multiple anomalies had a shorter survival (8 months) than patients with single anomalies (18 months) or those with a normal karyotype (36 months). All these differences were significant. The incidence of multiple anomalies was higher in patients with RAEB and RAEB-t than in those with RA, RARS, and CMMOL (p less than 0.05). However, no chromosome anomaly was specifically associated with any group of FAB classification. Transformation to acute leukemia was observed in 25% of patients with normal karyotype, 41% of patients with single anomalies, and 50% of patients with multiple changes. The incidence of leukemic transformation was significantly higher in patients with multiple anomalies than in those with a normal karyotype (p less than 0.05). Thus, in the present study, FAB classification and chromosome anomalies were of independent prognostic significance. Sequential cytogenetic studies were performed in 23 patients to correlate the cytogenetic and clinical findings during the course of the disease. Six of seven patients with transformation to acute leukemia showed a karyotypic evolution. These findings agree with the view that an unstable karyotype can be associated with a poor prognosis.

Adult↗
PubMed1990

Acute nonlymphocytic leukemia (ANLL) with isochromosome i(17q) as the sole chromosomal anomaly: a distinct entity?

3 patients with acute nonlymphocytic leukemia (ANLL) and an isochromosome (17q) as the sole chromosomal defect are reported. Besides this cytogenetic pattern, they shared several clinical and hematological features such as male sex, advanced age, spleno- and/or hepatomegaly and a suspected preceding myeloproliferative syndrome. Bone marrow cytology was characterized by hypercellularity, prominent baso- and eosinophilia, decreased erythropoiesis and marked increase of dysmorphic megakaryocytes. We suggest that some or most patients with ANLL and i(17q) as the sole cytogenetic defect represent blastic transformation of an underlying chronic myeloproliferative disorder rather than de novo ANLL.

Aged↗