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Biomedical subjects

W Queisser

Publications and source records attributed to W Queisser.

At least 19 recordsLinked to original sources
PubMed1999

Phase I trial of methotrexate-albumin in a weekly intravenous bolus regimen in cancer patients. Phase I Study Group of the Association for Medical Oncology of the German Cancer Society.

Methotrexate-albumin conjugate (MTX-HSA) is a novel human albumin-based prodrug conjugate of methotrexate (MTX). A low MTX loading rate provided optimal tumor targeting and therapeutic efficacy during preclinical testing. The objectives of this first Phase I study of MTX-HSA were to determine dose-limiting toxicity (DLT) and maximum tolerated dose (MTD) in a weekly regimen. Seventeen cancer patients who were no longer amenable to standard treatment were enrolled and were evaluable for DLT. Up to eight injections were performed in weekly intervals. Dose escalation was as follows: 20, 40, 50, and then 60 mg/m2 MTX-HSA (based on the amount of MTX bound to albumin). Additional MTX-HSA courses were feasible in case of tumor response. DLT (mainly stomatitis, Common Toxicity Criteria grade 3) occurred, beginning at the 50 mg/m2 dose level after repeated administrations; in one case, thrombocytopenia was dose-limiting. Two events of DLT occurred at the 60 mg/m2 dose level within the first two administrations. Mild anemia, transaminitis, and one case of skin toxicity were found. No significant leukopenia, nausea, renal toxicity, or other toxicities were observed. MTX-HSA was well tolerated. Drug accumulation occurred on the weekly schedule. The half-life of the drug was estimated to be up to 3 weeks. Tumor responses were seen in three patients: (a) a partial response was seen in one patient with renal cell carcinoma (response duration, 30 months, ongoing); (b) a minor response was seen in one patient with pleural mesothelioma (response duration, 31 months, ongoing); and (c) a minor response was seen in one patient with renal cell carcinoma (response duration, 14 months until progression). Poststudy treatment was administered at 2-4-week intervals. No signs of toxicity or drug accumulation were seen. Altered pharmacological properties of MTX-HSA such as plasma half-life, tumor targeting, or intracellular metabolism might have contributed to these responses. The MTD for weekly administration was 4 x 50 mg/m2 MTX-HSA during short-term treatment. A regimen with MTX-HSA injections of 50 mg/m2 every 2 weeks was recommended for a further clinical Phase I study.

Adolescent↗
PubMed1998

Should a platelet limit of 600 x 10(9)/l be used as a diagnostic criterion in essential thrombocythaemia? An analysis of the natural course including early stages.

In order to evaluate the natural history of essential thrombocythaemia (ET), clinical data and prognostic factors of 143 patients with ET were retrospectively analysed (mean observation time 6.1 +/- 4.6 years). In 42 patients the early phase of the disease with initial platelet counts between 250 and 600 x 10(9)/l was assessed. In most early cases, ET was suggested by clinical symptoms (79%) and increased megakaryopoiesis (95%) with abnormal megakaryocytes in bone marrow histology (n = 34) and cytology (n = 5). Other myeloproliferative disorders and reactive thrombocytosis were excluded according to the diagnostic criteria of the Polycythemia Vera Study Group. During follow-up of the 38 early cases not treated cytoreductively at diagnosis, the platelet counts increased to >600 x 10(9)/l in 28 patients (74%) and remained between 450 and 600 x 10(9)/l in 10 patients (26%). In primarily asymptomatic patients (n = 46) with initial platelet counts above (n = 37) and below 600 x 10(9)/l (n = 9) the rates of increase of symptomatic patients were similar at about 7% per year. No influence of the initial platelet count on survival was seen in multivariate analysis of prognostic factors which included all 143 cases. Survival was mainly influenced by the rate of ET-related complications during follow-up (P = 0.002). Analysing the influence of cytoreductive therapy on symptom-free survival, platelet reduction benefited patients under 60 years (19 cytoreductively treated v 65 untreated patients, P = 0.075). The results demonstrate the possible clinical relevance of the early stages of ET and suggest that the features of pathologic megakaryopoiesis in the bone marrow are a more reliable diagnostic criterion than a definite platelet limit. Therefore, further therapeutic studies should include all stages of the disease and all age groups.

Adult↗
PubMed1998

[Adjuvant radiochemotherapy with 5-FU and folinic acid in Dukes stage B and C rectum carcinoma: an interim analysis].

In a prospective multi-institutional German adjuvant trial patients with curatively resected rectal cancer (Dukes B or C) were randomly assigned to receive postoperative radiotherapy (50.4 Gy) and either 12 or 6 cycles of 5-fluorouracil and medium-dose folinic acid. Our preliminary results of the interim analysis, based on 206 patients, indicate that this adjuvant therapy is well tolerated by the patients and a prolonged chemotherapy over 12 months has no advantage over 6 months of chemotherapy. The relatively high rate of tumor recurrence (30.7%) after a median follow-up of 29.3 months in this trial emphasizes the need for dose intensification planned for a further trial.

Adult↗
PubMed1997

Comparative analysis of the impact of risk profile and of drug therapy on survival in CML using Sokal's index and a new score. German chronic myeloid leukaemia (CML)-Study Group.

Survival times in chronic myeloid leukaemia (CML) may vary widely depending on the risk profiles of patients. This fact is frequently not, or not sufficiently, considered in evaluating survival in CML, and some studies do not report risk profiles. Therefore we analysed the relative impact of risk profile and therapy on survival using the median survival times of therapy groups and of risk groups of the three-arm randomized German CML Study I (interferon alpha v hydroxyurea v busulphan; median survival times 65 v 56 v 45 months, n = 490, median observation time 70.4 months). The impact of risk profile (Sokal) on survival as determined by the survival difference between high and low risk patients (40 months) was twice the maximum survival difference between treatment groups (20 months). A similar ratio was obtained after stratification for therapy and for risk profile. Since Sokal's index has been reported to prognostically discriminate IFN-treated patients less well than chemotherapy-treated patients, a new score with better discrimination of IFN-treated patients was also used. The results were similar for both scores. We conclude that the risk profile at diagnosis is still more important for survival of CML patients than therapy. Therefore patients should be stratified according to risk profile for comparisons of survival times between studies and treatment arms.

Adolescent↗
PubMed1997

Randomized studies with interferon in chronic myelogenous leukemia (CML) and comparative molecular aspects. German CML Study Group.

Four randomized prospective studies on interferon alpha (IFN) in CML report varying degrees of prolongation of the chronic phase of CML and of survival as compared to conventional therapies. There is agreement that IFN prolongs survival as compared to standard busulfan. There is disagreement, however, as to which degree IFN is superior to hydroxyurea. Whereas the randomized studies of the Italian cooperative group and of the British MRC find a statistically significant survival advantage of IFN over hydroxyurea of about 20 months, this difference is only 10 months in the German randomized study and not significant. One reason for this difference might be the more intensive treatment schedule for the hydroxyurea control group in the German study. Other reasons might be differences in risk profiles between the patient groups studied and in strategies of IFN therapy. About 1% of the human genome consists of retroviral or retroviral-like sequences. By analogy to animal models, endogenous retroviruses might also have pathogenic potential in human disease. The transposon-like structure of retroviruses that enables them to integrate at almost any position in the host genome and the capability of retroviruses to serve as efficient vehicles of cellular genes are in support of a pathogenic potential. Furthermore, particles resembling retroviruses have been observed long ago in human embryonic and malignant tissues and cell lines. Sequence information and the transcriptional activity of the endogenous sequences argue against the possibility that these sequences are only fossil relics of early evolutionary periods. Most of the sequences appear to be inactivated by stop codons or frameshifts, making the genomic localization of open reading frames with biological activity difficult. Up to now, mutagenesis by insertion of retroviral-like sequences in sporadic cases of human disease appears to be the only example of pathogenic relevance of retroviruses in man.

Antineoplastic Agents↗
PubMed1996

[Intensive post-remission therapy in acute myeloid leukemia. Results of a prospective comparative study by the South Germany Hemoblastosis Group].

BACKGROUND: To study intensive postremission therapy in adult patients with acute myeloid leukemia myeloablative therapy followed by allogeneic or unpurged autologous bone marrow transplantation (BMT) was compared with high-dose cytosine-arabinoside/daunorubicin (HDAC) consolidation. PATIENTS AND METHODS: 148 de novo AML patients of maximum 50 years (median 36 years, range 16 to 50) were enrolled in the trial. Following induction and early consolidation chemotherapy consisting of daunorubicin, cytosine-arabinoside and VP-16 (DAV), patients with an HLA-identical sibling underwent allogeneic BMT. The other patients received (by randomization or patient's decision) either HDAC or high-dose busulfan plus cyclophosphamide followed by autologous BMT. RESULTS: Hundred and five 105 (70.9%) patients achieved a complete remission. The event-free survival rates after intensive postremission therapy after 72 months were: after BMT (24 patients) 62% (95% confidence interval +/- 19%), after HDAC (44 patients) 36 +/- 16% and after autologous BMT (12 patients) 18 +/- 22%. Thus allogeneic BMT was superior to autologous BMT (p = 0.04), as was HDAC compared to autologous BMT, although not significantly so (p = 0.15). Patients receiving 2 cycles of HDAC had a better 6-year event-free survival rate (47%) and a lower relapse rate (50%) than patients who received only 1 course (29% and 70% respectively). CONCLUSIONS: High-dose busulfan/cyclophosphamide followed by unpurged autologous BMT early after achieving CR had no advantage over high-dose ara-c/daunorubicin. Two cycles of HDAC yielded better results than 1 cycle. The highest event-free survival rate was reached with myeloablative therapy followed by allogeneic BMT.

Adolescent↗
PubMed1996

Randomized study of the combination of hydroxyurea and interferon alpha versus hydroxyurea monotherapy during the chronic phase of chronic myelogenous leukemia (CML Study II). The German CML Study Group.

It is the long-term goal of the German CML Study Group and of the Süddeutsche Hämoblastosegruppe (SHG) to improve survival of patients with chronic myelogenous leukemia (CML). In a first randomized study (CML Study I) monotherapies with hydroxyurea or interferon alpha (IFN-alpha) were compared with a standard busulfan regimen with regard to duration of the chronic phase and survival. The main results of this study were published, 1-3 and a long-term follow up is planned. In a second randomized study the effect of the combination of IFN-alpha and hydroxyurea versus hydroxyurea monotherapy on survival is being investigated. This paper provides a first preliminary report on the study concept, patient recruitment, state of documentation and initial patients' characteristics 9 months after closure of the study.

Adult↗
PubMed1994

Randomized comparison of interferon-alpha with busulfan and hydroxyurea in chronic myelogenous leukemia. The German CML Study Group.

As curative bone marrow transplantation is available only to a minority of patients with chronic myelogenous leukemia (CML), drug therapy remains of central interest. Several nonrandomized studies have suggested that interferon-alpha (IFN) may prolong survival in CML. In a randomized multicenter study the influence of IFN versus busulfan or hydroxyurea (HU) on survival of Philadelphia-positive (Ph+) CML was examined. A total of 513 Ph+ patients were randomized for treatment as follows: 133 for IFN, 186 for busulfan, and 194 for HU. IFN-treated CML patients have a significant survival advantage over busulfan-treated (P = .008), but not over HU-treated patients (P = .44). The longer survival is due to slower progression to blast crisis. Median survival of IFN-treated patients is 5.5 years [5-year survival, 59%; 95% confidence interval (CI), 48%-70%], of busulfan-treated patients, 3.8 years (5-year survival, 32%; CI, 24%-40%), and of HU-treated patients, 4.7 years (5-year survival, 44%; CI, 36%-53%). Patients who continue on IFN survive longer than those in whom IFN is discontinued before blast crisis (P = .007). Complete hematologic IFN-responders have a survival advantage over partial responders or nonresponders (P = .02). Cytogenetic IFN-responders have no significant survival advantage over nonresponders (P = .2). Patients who attain white blood cell (WBC) counts of 10 x 10(9)/L or less have a survival advantage in the IFN (P = .007) and HU (P = .05) groups. Whereas toxicity in the IFN group was considerably higher than in the busulfan or HU groups, long-lasting cytopenias necessitating discontinuation of therapy as observed with busulfan have not been seen with IFN or HU. The problems of conventional prognostic scores (Sokal's score, Score 1) that we observed in IFN-treated patients support the idea that IFN changes the natural course of CML. We conclude that, with regard to survival of CML in the chronic phase, IFN is superior to busulfan and as effective as HU. Whether and to what extent IFN is superior to HU appears to depend, at least in part, on the degree of WBC suppression by HU-therapy and on the risk profile of the patients.

Adolescent↗
PubMed1994

A case of pure red cell aplasia: follow-up on different immunosuppressive regimens.

A 66-year-old patient was admitted to our hospital in January 1992 for further evaluation of severe normocytic anemia. Hemoglobin (Hb) was 3.5 g/dl, reticulocyte count 1%. Bone marrow showed a nearly complete lack of red cell precursors, thus favoring the diagnosis of acquired pure red cell aplasia (PRCA). Immunosuppressive therapy with prednisolone was started but had to be supplemented with azathioprine because of a further rapid decrease in Hb to 3.7 g/dl after an initial transfusion of 6 U red blood cells. However, with this regimen a renewed decrease in Hb to 6.6 g/dl was noted, and further transfusions were required. Therefore therapy was switched to cyclosporine A (CyA) while tapering off prednisolone. Four months after the initial diagnosis a positive parvovirus B19 IgM antibody was found. After the failure of hematological remission with three immunosuppressive regimens a course of high-dose intravenous immunoglobulins (IVIG) was administered in July 1992. Six weeks after IVIG therapy a peak hemoglobin concentration of 12.3 g/dl was noted, and further transfusion was not required. CyA was tapered off in October 1992. One month later CyA was reinstituted because of a relapse of PRCA but was unsuccessful until January 1993. At this time immunosuppressive CyA therapy was discontinued because of a periodontal abscess. In February 1993 a second IVIG infusion was given, and a second remission of PRCA was noted, showing an increase in hemoglobin up to 14.5 g/dl by November 1993. At the last follow-up visit in February 1994 our patient was still in complete hematological remission.

Aged↗
PubMed1993

Randomized comparison of busulfan and hydroxyurea in chronic myelogenous leukemia: prolongation of survival by hydroxyurea. The German CML Study Group.

In a randomized multicenter study the influence of hydroxyurea versus busulfan on the duration of the chronic phase and on survival of chronic myelogenous leukemia (CML) was determined. In addition cross resistance and adverse reactions of the drugs were analyzed. From July 1983 to January 1991, 441 CML patients were randomized to receive hydroxyurea or busulfan. Of these, 90.7% were Philadelphia positive; 25.7% were low, 38.2% intermediate, and 36.2% high risk patients according to Sokal's score. The median survival of the busulfan treated Philadelphia-positive patients is 45.4 months and of the hydroxyurea group 58.2 months (P = .008). The survival advantage for the hydroxyurea treated patients is recognized in all risk groups. Sixty four patients reached therapy resistance before blast crisis and were crossed over to the alternative drug. The 23 patients with primary hydroxyurea had a median survival of 5.6 years, the 41 patients with primary busulfan therapy a median survival of 2.7 years (P = .02). Adverse reactions were less frequent with hydroxyurea with no severe adverse effects (lung fibrosis, long lasting bone marrow aplasia). The analysis of white blood cell counts in the course of treatment showed lower counts in the hydroxyurea patients. We conclude that hydroxyurea is superior to busulfan in therapy of CML in chronic phase and should be used as first line therapy. Busulfan may have a role as secondary therapy after hydroxyurea resistance or intolerance.

Blast Crisis↗
PubMed1993

Randomized phase II study of single-agent epirubicin +/- verapamil in patients with advanced metastatic breast cancer. An AIO clinical trial. Arbeitsgemeinschaft Internistische Onkologie of the German Cancer Society.

BACKGROUND: Anthracyclines are the most active cytostatic agents in patients with metastatic breast cancer. Drug resistance and dose intensity are relevant issues in the treatment of cancer. METHODS: A randomized phase II study in 51 patients with advanced progressive metastatic breast cancer was performed. Twenty-six were treated with epirubicin (EPI) 120 mg/m2 i.v. bolus injection divided over three days combined with a daily dose of 480 mg verapamil (VPL) orally administered one day before and during EPI. Twenty-five patients received the same dose and schedule of EPI without VPL. Evaluation of response was carried out after three 21-day cycles. Study endpoints were objective response rate and overall survival. RESULTS: Among the 24 evaluable patients treated with EPI+VPL 1 CR (4%), 7 PR (29%), 9 NC (38%) and 7 PD (29%) were observed. Two patients were excluded because of toxicity. Among the 24 evaluable patients treated with EPI alone 8 PR (28%), 6 NC (24%) and 10 PD (40%) were observed, and one patient was excluded because of toxicity. Myelotoxicity was the major side effect followed by alopecia, stomatitis/mucositis and nausea. The patient group treated with VPL had lower blood pressure levels during therapy, with complete normalization after discontinuation of VPL. The median overall survival times were similar: 7.4 month in the EPI group and 8.9 month in the EPI+VPL group. CONCLUSION: In both treatment groups the objective response rate was about 30% and the overall survival rates were also the same. No clinical relevance could be demonstrated for the hypothesized resistance modifying action of VPL. Furthermore, VPL did not increase the toxicity of EPI.

Adult↗
PubMed1991

Oral administration of idarubicin as first line cytostatic therapy in patients with metastasized breast cancer and favourable prognosis. A trial of the phase II study group of the Association for Medical Oncology of the German Cancer Society.

Idarubicin is a new anthracycline derivative with therapeutic efficacy in metastatic breast cancer. In a phase II trial we treated 23 patients with advanced breast carcinoma and favourable prognostic factors. Oral dose of idarubicin was 15 mg/m2 day 1-3 repeated every 3 weeks. All patients were pretreated with hormones. Idarubicin was administered as first line chemotherapy. 20 patients were evaluable for response: 3 patients achieved partial remission, 12 patients stable disease; tumour progression occurred in 5 patients. 3 patients were not evaluable for response because only 1 treatment cycle was administered. Main toxicites were leukopenia (median WHO-grade: 2,r:0-4), nausea and vomiting (median: 1,r:0-4) and alopezia (median: 1,r:0-3). 1 patient died in septic shock: Immediately after the administration of one idarubicine cycle, she was extensively irradiated because of bone metastasis. The fatal course of the disease in this patient does not depend only on the idarubicin therapy, but also on the extensive bone infiltration and on intensive radiation therapy. Idarubicin proved to be an effective drug in metastatic breast cancer with low systemic toxicity and the advantage of oral administration. The drug is an enrichment of therapeutic armament, especially in patients with soft tissue and bone metastasis.

Administration, Oral↗
PubMed1991

Phase II study of vinorelbine by oral route (in a hard gelatine capsule) for metastatic breast cancer patients. A trial of the phase I/II study group of the Association for Medical Oncology of the German Cancer Society.

17 patients with advanced low-risk breast carcinoma not previously pretreated by cytostatic agents were treated by Vinorelbine (VIN), 5'-Nor-anhydro-vinblastine, a new semisynthetic compound of the vinca alkaloid series. A dose of 130 mg per week was administered in a hard gelatine formulation for at least eight weeks. Out of 15 evaluable patients, no complete or partial remission was observed. However, there were 9 patients (60%) achieving no change and tumor stabilization, respectively, lasting for a median of 3.0 months. Main toxicities were leukopenia (17.7%, WHO grade 3-4), nausea and vomiting (17.7%, WHO grade 3-4), and acute diarrhea (70.6%, WHO grade 1-4). Thus, further trials with the oral medication used for this study are not recommended.

Aged↗
PubMed1990

[Treatment of advanced pancreatic cancer with 5-fluorouracil, 4-epidoxorubicin and mitomycin C (FEM II). From the Chemotherapy of Gastrointestinal Tumors Group].

In a multicentre phase II trial, 20 patients with advanced pancreatic carcinoma were treated with 5-fluorouracil, 4-epidoxorubicin and mitomycin C, in which 4-epidoxorubicin was administered by escalated dose and split course (FEM II). From among 12 patients evaluable for response, 2 partial and 1 minimal remission were observed, suggesting a response rate of 25%. Four patients (30%) showed a no change and 5 progression. The median survival of all patients was 3.4 months, of the responders 8.4 months, of those with no change 5.2, and of those showing progression 3.4 months. Considerable nausea/vomiting and leukopenia was observed. The preliminary data suggest that the FEM II regimen does not offer any progress in terms of efficacy, survival and toxicity for advanced pancreatic carcinoma.

Adult↗
PubMed1990

Phase II evaluation of carboplatin in advanced esophageal carcinoma. A trial of the Phase I/II Study Group of the Association for Medical Oncology of the German Cancer Society.

Eighteen patients with advanced squamous cell carcinoma of the esophagus without prior chemotherapy were treated with carboplatin. Based on experimental data a split dose of carboplatin of 130 mg/m2 given on days 1, 3 and 5 was administered. In cases showing no WBC and platelet suppression, an escalated dose of 160 mg/m2 was proposed. Out of 18 evaluable patients no complete and partial responses were observed and there were only 5 patients with stable disease (27.8%) lasting 2-7 months. Therefore, carboplatin in the regimen used shows no meaningful antitumor activity in patients with advanced esophageal carcinoma. The escalated dose (mean 107-123% of the starting dose) was well tolerated and was followed by only minor gastrointestinal and hematological toxicity. Therefore, this regimen can be recommended for future trials.

Adult↗
PubMed1990

Etoposide, adriamycin, and cisplatinum (EAP) combination chemotherapy for advanced gastric cancer. A phase II trial by the "Chemotherapiegruppe Gastrointestinaler Tumoren (CGT)".

In a multicenter trial, 49 patients with histologically proven advanced gastric cancer were treated with a combination chemotherapy consisting of etoposide 120 mg/m2 d 4, 5, 6 adriamycin 20 mg/m2 d 1, 7 and cisplatinum 40 mg/m2 d 2, 8. Therapy was repeated every 4 weeks, 45 patients were evaluable for response after 8 weeks of treatment. Eight patients achieved a partial remission (PR: 18%), 17 patients had no change (NC: 38%), and 20 patients showed tumor progression (P: 44%). Four patients with primarily inoperable tumor and without distant metastases who achieved a partial remission, underwent second look operation with curative intention. All 4 patients died within 12 months after second look operation due to tumor recurrence. Median survival time of all patients was 9 months. Toxicity was considerable. WHO grade 3/4 toxicity appeared in 20-30% of patients (nausea, vomiting, loss of appetite, leucopenia). After 3 cycles complete alopecia was present in 70% of patients. Severe infection, requiring treatment, occurred in 10 patients. Five patients discontinued therapy because of intolerable subjective toxicity. The observed response rate of 18% objective partial remissions is disappointing and does not give support to the communications reporting response rates over 50% with EAP and other regimens including cisplatinum. In conclusion, and considering the high subjective and objective toxicity of this regimen, it can not be recommended for standard use in patients with advanced gastric cancer.

Antineoplastic Combined Chemotherapy Protocols↗