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D K Hossfeld

Publications and source records attributed to D K Hossfeld.

At least 145 records · Page 8Linked to original sources
PubMed1992

Tissue disposition and plasma concentrations of idarubicin after intravesical therapy in patients with bladder tumors.

We studied single doses of intravesical idarubicin (IDA) given as 1-h instillations to 33 patients with bladder tumors. The dose was escalated from 5 to 30 mg and the concentration, from 0.25 to 1.5 mg/ml for evaluation of the importance of both the total amount of drug and the drug concentration on the levels of IDA found in different tissues (tumor, mucosa and muscle). Additionally, plasma uptake over 24 h was studied. The results demonstrated that (1) the levels of IDA in extracts of bladder tumors were significantly higher than those in normal bladder tissue, (2) the incorporation of IDA into tumors depended on the total amount of drug instilled and on the concentration of drug in the instillation fluid, (3) cytotoxic concentrations of IDA were noted in all tumors when the total amount of drug instilled was greater than 15 mg and the drug concentration in the instillation fluid was greater than 0.33 mg/ml, and (4) plasma levels of IDA were negligible.

Administration, Intravesical↗
PubMed1992

Cytogenetics in multiple myeloma and plasma cell leukemia: simultaneous cytogenetic and cytologic studies in 51 patients.

Cytogenetic studies in patients with multiple myeloma (MM) and plasma cell leukemia (PCL) have in general been largely unsuccessful. The investigation of mitoses of nonmalignant hematopoietic precursor cells, rather than mitoses of malignant plasma cells might account for the low percentage of pathological genetic findings. We investigated bone marrow (BM) cells of 51 patients both cytogenetically and cytologically. In patients with a normal karyotype (n = 39) nearly all mitoses examined cytologically (107/117) derived from granulopoietic or erythropoietic cell lineages. In contrast, 20/27 metaphases in patients with a pathological karyotype (n = 12) were found to be plasma cell mitoses. These findings may explain the low rate of chromosomal rearrangements in MM and may suggest that the real abnormality rate is considerably higher.

Bone Marrow↗
PubMed1992

Clinical and prognostic significance of the Philadelphia chromosome in adult patients with acute lymphoblastic leukemia.

Between 1983 and 1991 the Philadelphia chromosome (Ph1) was found in bone marrow and/or peripheral blood cells of 25 adult patients with acute lymphoblastic leukemia (ALL). The Ph1 as sole anomaly was seen in 13 patients, while six patients had additional structural and another six structural and numerical aberrations. Most patients (23/25) received combination chemotherapy according to the BMFT protocols 1/81, 2/84, 3/87, and 4/89. For 25 evaluable patients two early deaths, two treatment failures, two partial remissions (PR), and 19 complete remissions (CR) after phase 1 or 2 of the induction regimen were recorded. Two of these 19 patients who achieved CR are presently disease free, whereas 17 have relapsed after a median duration of remission of 9 months. Actuarial median survival for all patients was 13 months. The probability of continuous complete remission (CCR) after 39 months, as well as that of survival after 40 months, is only 6%. Our results confirm that the presence of the Ph1 is associated with a poor prognosis in adult-ALL patients. Therefore, whenever first CR is obtained and an HLA-identical donor is available, allogeneic bone marrow transplantation (BMT) should be performed at once, the more so, since transplantation in second CR seems to offer no cure. Future studies will have to show whether an intensified cytotoxic therapy can improve the prognosis of Ph1(+)-ALL.

Adult↗
PubMed1992

A phase II study of sequential recombinant interleukin-2 followed by dacarbazine in metastatic melanoma.

16 patients with disseminated malignant melanoma (1 with primary ocular melanoma) entered a multicentre phase II study of recombinant interleukin-2, (rIL-2) given by continuous intravenous infusion on days 1-5 at 18 x 10(6) IU/m2 per day, followed by dacarbazine 850 mg/m2 on day 8. After a 2 week rest, a second course was given. In the absence of disease progression, monthly maintenance cycles were given for up to four cycles. 16 patients received one cycle, 14 received two and 6 patients three or more. All 16 patients are evaluable for toxicity and 15 for response. 2 patients responded (13%). 1 patient with lung and pleural metastases achieved partial remission after two cycles and went off treatment after six cycles. 3 months later a complete response was noted lasting 396+ days. A second patient with lung metastases had a partial response lasting 153 days. 3 patients (20%) had stable disease. Mean rebound lymphocytosis (24-48 h after the end of rIL-2 therapy), cell count 4.9 x 10(9)/l (2.6-8.8 x 10(9)/l) was within the expected limits. Other toxicity was as expected. Thus sequential treatment with rIL-2 and dacarbazine is feasible but synergy did not occur.

Adult↗
PubMed1992

Comparison of chromosome analysis and BCL-1 rearrangement in a series of patients with multiple myeloma.

Translocation (11;14)(q13;q32) is a recurring chromosome abnormality which is found non-randomly in non-Hodgkin's lymphoma, especially of follicular type, as well as in B-cell chronic lymphocytic leukaemia, Waldenström's macroglobulinaemia and multiple myeloma. To define further the prevalence of this abnormality in multiple myeloma, we studied a series of 17 patients with this disease with concomitant chromosome analysis and Southern blotting, using a probe specific for the major translocation cluster of the BCL-1 oncogene which is located at chromosome 11q13. Karyotype analysis of 14 evaluable patients revealed three cases with abnormalities of chromosome 11q13, two of them with t(11;14)(q13;q32) and one with del (11)(q13). Southern blot analysis showed no rearrangements in BclI and HindIII digests of DNA from 17 patients including the three patients with anomaly of chromosome 11q13, using a BCL-1 specific probe. A possible restriction length polymorphism was detected in EcoRI cut DNA of five out of 11 patients studied. Therefore the chromosomal break point in our cases with abnormality of chromosome 11q13 must lie outside the major translocation cluster of the BCL-1 gene. However, in centrocytic lymphoma rearrangement of the BCL-1 oncogene has been detected in up to 50% of cases. Location of the break point may therefore be dependent on the differentiation of the transformed B-cell.

Adult↗
PubMed1992

Carboplatin/etoposide/vincristine therapy 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 4-year survival rates are 26% in limited disease and 8% 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 are higher in the CEV arm (CR 32 vs. 17%, CR + PR 80 vs. 60%), with statistically significant difference. 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.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1992

Combination chemotherapy with carboplatin, etoposide, and vincristine as first-line treatment in small-cell lung cancer.

PURPOSE: The antineoplastic activity of carboplatin and etoposide may be improved by the addition of vincristine (CEV) because of its low myelosuppressive potential and its activity in small-cell lung cancer (SCLC). A phase II study with CEV was carried out. PATIENTS AND METHODS: One hundred twenty-one untreated patients with SCLC (63 with limited disease [LD], 58 with extensive disease [ED]) were treated with a combination of 300 mg/m2 intravenous (IV) on day 1, etoposide 140 mg/m2 IV daily on days 1 to 3, and vincristine 1.4 mg/m2 IV on days 1, 8, and 15 every 4 weeks. RESULTS: A 90% rate overall response rate including 56% complete responses (CRs) was achieved in LD and an 83% overall response rate including 35% CRs was observed in ED. Median survival time was 13 months in limited disease and 9.5 months in extensive disease. The 24 and 36 months survival rates were 29% in LD and 9% in ED. Myelosuppression was the main form of toxicity. CONCLUSION: The combination of CEV is a new active and well-tolerated regimen in the treatment of SCLC. Prospective randomized studies of CEV with conventional chemotherapy are warranted.

Adult↗
PubMed1992

Phase II and III studies with carboplatin in small cell lung cancer.

Carboplatin is one of the most active agents in untreated small cell lung cancer (SCLC) (11% complete response [CR], 59% CR plus partial response [PR]). Combination carboplatin/etoposide/vincristine (CEV) (phase II trial) led to an overall remission rate of 84% in patients with limited disease (LD), with 52% CRs. The median survival time with this combination was 14 months in patients with LD and 9.5 months in those with extensive disease (ED). The 30-month survival rates are 30% in LD and 10% in ED, which represents 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 ED patients, CR and overall response rates to date are higher in the CEV arm (CR, 20% versus 15%; CR plus PR, 83% versus 65%), 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 are presented.

Adult↗
PubMed1992

[Prevalence of hepatitis C virus in poly-transfused patients with hematologic and oncologic diseases].

Patients with hematological and oncological diseases often require intensive, supportive hematotherapy due to the underlying disease or chemo-/radiotherapy. As a consequence, they had an increased transfusion-associated risk of hepatitis C virus infections (non-A, non-B-posttransfusion hepatitis) until 1989-1990, when specific and sensitive HCV antibody tests became available. This is confirmed by our study of 'first' and 'second' generation (1.0 and 2.0) anti-HCV EIAs against structural and non-structural (NS) antigen-determinants. Ten of 101 patients (10.9%) were anti-HCV positive in 2.0 tests. HCV antibodies were detected more often by 2.0 EIAs and the new HCV-immunoblot (4-RIBA), than by 1.0 EIAs. In this respect, the patients' serological HCV profile differs from that of healthy blood donors, which display a prevalence of NS-antibodies.

Adolescent↗
PubMed1992

Pharmacodynamic and pharmacokinetic aspects of iodo-doxorubicin.

Iodo-doxorubicin (I-DOX) is a new doxorubicin (DOX) analog presently in phase II clinical trials in Europe. This drug is similar to DOX in its metabolism but differs in its pharmacokinetics. We describe correlations between pharmacokinetic parameters and toxicity. There is a linear relationship between the dose in mg/m2 and the nadirs of the reduction in white blood cells (WBC), neutrophils (PMN), platelets (PLT), and hemoglobin (HB). Furthermore, a linear correlation exists between the dose in mg/m2 and the area under the curve (AUC) of I-DOX. The relationship between the AUC of I-DOX and the reduction of PMNs plotted on a logarithmic scale shows a sigmoidal curve, whereas no such correlation was found between I-doxorubicinol, the major cytostatic metabolite, and the reduction in PNMs. The variation in the AUC for I-DOX correlated with the relative amount of metabolism of I-DOX. A correlation existed between the relative amount of metabolism of I-DOX and the reduction in PNMs. These results may have an impact on the evaluation of I-DOX in phase II trials, since a sound understanding of the pharmacokinetic/pharmacodynamic relationships can yield important information for minimizing unacceptable toxicity during phase II, as well as phase III, trials.

Biotransformation↗
PubMed1992

Chronic myelogenous leukemia: recent developments in prognostic evaluation and chemotherapy. The German CML Study Group.

Recent developments in CML research are illustrated by the results of one large randomized multicenter study carried out by the German CML Study Group. From July 1983 to January 1991, a total of 703 CML patients were recruited; 624 patients were randomized to compare hydroxyurea and interferon alpha (IFN) with busulfan. The median survival of Ph+ patients by now is 3.95 years, that of Ph- patients 1.1 years. Some difference in survival is recognizable between the treatment arms, but this is not yet significant. Fewer adverse effects are being observed in the hydroxyurea group. Ph-negative patients tend to have lower white blood cell and platelet counts. Patients (164) were randomized to receive IFN. In 50 patients (30%) IFN had to be terminated because of adverse effects, therapy resistance, or other reasons. Reduction of the Ph-chromosome was observed in 20% of evaluable patients. In 3 patients complete cytogenetic remissions were observed. Clinically relevant neutralizing antibodies were detected in 9 cases. Prospectively evaluated age, organomegaly related symptoms, Karnofsky index, extramedullary manifestations, erythroblasts, and percent of circulating blasts proved to be of prognostic significance. A prognostic score (score 1) was determined and compared to Sokal's score. It is expected that the study results will allow statements as to the advantages or disadvantages of the use of busulfan, hydroxyurea and IFN in the treatment of CML as well as to the reliability of prognostic markers.

Bone Marrow Transplantation↗
PubMed1991

A phase II combination trial with recombinant human tumor necrosis factor and gamma interferon in patients with colorectal cancer.

Recombinant human tumor necrosis factor (TNF) is a cytotoxic monokine with immunomodulatory functions. Gamma interferon (g-IFN) synergizes with TNF in many ways. We therefore conducted a Phase I/II combination trial with TNF and g-IFN at an immunomodulatory dose level in 16 patients with colorectal cancer. TNF (50 micrograms/m2 in a 30 min infusion) and g-IFN (100 micrograms in subcutaneous injections) were administered daily Monday through Friday for 4 weeks. Two cases of major toxicity, one acute renal failure and one case of severe thrombocytopenia, led to discontinuation of study medication in these patients. Toxicities in remaining patients were manageable with conservative treatment. Changes in laboratory values included leukopenia, anemia and thrombocytopenia. Alterations in lipid metabolism and changes in serum levels of acute phase proteins were observed. Increase in both total lymphocytes and a Leu 11 positive subpopulation, as well as an induction of measurable interleukin 2 serum levels in a subgroup of patients, were noted. Response results of 14 evaluable patients were one patient with a mixed response, 4 with stable disease and 9 with disease progression. Median survival was 23.5 weeks with only one patient alive after 71 weeks. Therefore the drug combination of TNF/g-IFN in the chosen regimen cannot be recommended for the treatment of patients with colorectal cancer.

Adult↗
PubMed1991

Translocation (14; 18) and (8; 22) in three patients with acute leukemia/lymphoma following centrocytic/centroblastic non-Hodgkin's lymphoma.

Three patients with centrocytic/centroblastic lymphoma developed a rapidly fatal leukemic transformation of the disease after a transient remission. At the time of transformation, cytogenetic analysis revealed in all patients abnormal karyotypes with coexistence of t (14; 18) and t (8; 22). Molecular analysis in one patient showed rearrangement of the BCL 2 oncogene and c-myc m-RNA expression. These findings imply that translocation t (14; 18) was present during the first phase of the disease and that acquisition of translocation t (8; 22) was accompanied by leukemic transformation.

Acute Disease↗
PubMed1991

A randomized trial with mitomycin-C/ifosfamide versus mitomycin-C/vindesine versus cisplatin/etoposide in advanced non-small-cell lung cancer.

192 evaluable patients with advanced inoperable non-small-cell lung cancer were treated with either mitomycin-C/ifosfamide (A), mitomycin-C/vindesine (B), or cisplatin/etoposide (C) in a prospective randomized trial. The response rates for each treatment arm were 30.0% (A), 22.7% (B), and 25% (C), respectively. There was no statistically significant difference (p = 0.4) between treatment arms. The median survival time was 27 weeks (A), 23 weeks (B), and 25 weeks (C), respectively. With regard to toxicity the combination mitomycin-C/vindesine was superior to treatment arms A and C. Nausea and vomiting (WHO 3 + 4) occurred only in 6.1% of the patients versus 43.3% of those treated with mitomycin-C/ifosfamide and 36.7% of those treated with cisplatin/etoposide. This difference is statistically highly significant (p = 0.0001). Because of its very low toxicity, especially for gastrointestinal symptoms, the combination mitomycin-C/vindesine was judged superior to the other combinations. None of these regimens, however, had a major impact on survival in advanced non-small-cell lung cancer.

Adult↗