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Eberhard Riedel - One of the best experts on this subject based on the ideXlab platform.

  • cellular kinetics of Prednimustine versus chlorambucil plus prednisolone in vitro
    Cancer Chemotherapy and Pharmacology, 1992
    Co-Authors: Eugen Musch, Mouhamad Malek, Jasna Peterkatalinic, Heinz Egge, Hermann Rink, B Lathan, Eberhard Riedel
    Abstract:

    Intracellular concentrations of Prednimustine (PM), chlorambucil (CLB), phenylacetic acid mustard (PAAM) and prednisolone (P) were measured in different experimental tumor cell lines that had been incubated with either PM or CLB+P. For intracellular analytical determination, we modified a high-pressure liquid chromatographic method for the detection of these substances in plasma. Intact PM could be detected in the intracellular compartment of the incubated tumor cells. PM-incubated cells from PM-injected rats exhibited a higher intracellular concentration-time integral (PAAM) and longer concentration-time profiles for drugs with alkylating capacity than did cells exposed to the CLB+P mixture or to CLB. PAAM was not detectable after incubation of cells with PM, whereas in CLB-incubated cells the AUC of PAAM exceeded that of the parent drug CLB. Our in vitro results therefore favour the concept of a facilitated intracellular uptake and an increased antiproliferative effect for PM versus CLB and CLB+P.

  • comparative pharmacokinetics of chlorambucil and Prednimustine after oral administration
    Oncology, 1991
    Co-Authors: Ulrich Loos, Eugen Musch, Mouhammad Malek, Eberhard Riedel
    Abstract:

    The pharmacokinetics of chlorambucil, phenylacetic acid mustard (the beta-oxidation product of chlorambucil), and prednisolone were investigated in a cross-over study after oral administration of chlorambucil (30 mg) + prednisolone (50 mg) versus Prednimustine (300 mg), the ester of chlorambucil and prednisolone. Intact Prednimustine could not be detected in plasma at any time. After administration of Prednimustine, the plasma concentration-time curves of chlorambucil, phenylacetic acid mustard, and prednisolone showed a retarded profile compared to the administration of the single components. The mean bioavailability was 14% for chlorambucil, 21% for phenylacetic acid mustard, and 22% for prednisolone, when given as Prednimustine, compared to the administration of free compounds in stoichiometrically equivalent doses. When given in the oral dosages mentioned above, the average dose-intensity was 62% for chlorambucil, 95% for phenylacetic acid mustard, and 72% for prednisolone, indicating sufficient therapeutic concentrations of the detectable agents.

B Nilsson - One of the best experts on this subject based on the ideXlab platform.

  • Prednimustine sterecyt versus cyclophosphamide both in combination with methotrexate and 5 fluorouracil in the treatment of advanced breast cancer
    European Journal of Cancer, 1993
    Co-Authors: H Yosef, A Slater, C W Keen, J S Bunting, H Hopestone, H Parmar, J T Roberts, B Termander, B Nilsson
    Abstract:

    153 women with advanced breast cancer were randomly allocated for treatment with SMF [Prednimustine (Sterecyt) + methotrexate + 5-fluorouracil, 83 patients] or CMF (cyclophosphamide + methotrexate + 5-fluorouracil, 70 patients). Prednimustine was administered orally 100 mg/m 2 daily, for 5 days, and cyclophosphamide was administered orally 100 mg/m 2 , for 14 days, each, every 4 weeks. Methotrexate was given at a dose of 40 mg/m 2 and 5-fluorouracil at 600 mg/m 2 on day 1 and 8, every 4 weeks. Leucovorin was used in 39 patients to alleviate mucositis. The two treatment groups were balanced in terms of age, performance status, lymph node status, histology, menopausal status and previous therapy. Response was evaluated in 140 patients. Of 76 patients treated with SMF, 4 had a complete and 21 a partial response (CR + PR = 33%), 40 had no change (NC) and 11 had progressive disease (PD). Of 64 patients treated with CMF, 3 had a complete and 18 a partial response (CR + PR = 33%), 30 had no change (NC) and 13 had progressive disease (PD). Time to treatment failure and survival were similar in both groups. A relationship between haematological and gastrointestinal toxicity and therapeutic efficacy was demonstrated with a superior survival and response rate recorded for patients with such toxicity than in patients without. Haematological toxicity was, in general, mild to moderate with no difference between the two groups. Alopecia ( P = 0.008), nausea/vomiting ( P = 0.02) and euphoria ( P = 0.03) were more common in the CMF-treated group. Diarrhoea was more common in the SMF group ( P = 0.03). In conclusion, SMF seems to be as efficient as CMF with regard to response rate, time to treatment failure and survival. However, SMF was tolerated better than CMF.

W Hiddemann - One of the best experts on this subject based on the ideXlab platform.

  • response to cytarabine ocfosfate ynk01 in a patient with chronic lymphocytic leukemia refractory to treatment with chlorambucil prednisone fludarabine and Prednimustine mitoxantrone
    Annals of Hematology, 1996
    Co-Authors: J Braess, W Hiddemann, W Kern, M Unterhalt, C C Kaufmann, B Ramsauer, M Schussler, A Kaeserfrohlich, E Schleyer
    Abstract:

    Cytarabine ocfosfate (YNK01) is a novel orally applicable prodrug of cytosine arabinoside. Recent pharmacokinetic studies have revealed a prolonged release of the cytotoxic agent cytosine arabinoside (araC) from hepatocytes into the systemic circulation, resulting in a half-life of approximately 24 h for araC. The specific pharmacokinetic characteristics of cytarabine ocfosfate lead to a prolonged exposure of leukemic cells to this antineoplastic agent during the 14-day cycle. The oral applicability during outpatient treatment and the sustained antineoplastic activity of araC against slowly proliferating leukemic B-cells suggest that cytarabine ocfosfate might be a useful drug in the treatment of chronic lymphocytic leukemia. Four years after diagnosis of B-CLL, a 50-year-old patient was started on cytarabine ocfosfate. Sequentially, the patient's disease had proved refractory to treatment with chlorambucil/prednisone (31 months), fludarabine (5 months), and Prednimustine/mitoxantrone (3 months). These established regimens were discontinued because of increasing lymphocytosis, significant thrombocytopenia, and progressive B-symptoms. Following three cycles of cytarabine ocfosfate B-symptoms resolved, lymphadenopathy disappeared, and thrombocytopenia was significantly reduced. The patient has been free of these symptoms on a dosage of 1500 mg cytarabine ocfosfate/day (cycle of 14 days with intervals of 14–21 days) for 24 months and remains in an ongoing partial remission.

  • Prednimustine and mitoxantrone in the treatment of low grade non hodgkin lymphomas
    1996
    Co-Authors: Michael Unterhalt, Peter Koch, C Potthoeck, R Herrmann, W Hiddemann
    Abstract:

    In 1988, Landys et al. reported a high anti-lymphoma activity of the combination of Prednimustine and mitoxantrone (PmM). These data were confirmed by a phase II study of our group in 19 pretreated patients with advanced low malignant non-Hodgkin lymphomas using PmM (Prednimustine 100 mg/m2/day orally days 1–5 and mitoxantrone 8 mg/m2/day i.v. days 1 and 2) with a response rate of 68%. Based on these data a randomized multicenter comparison of PmM with standard COP (cyclophosphamide 400 mg/m2/day i.v. days 1–5, vincristine 1,4 mg/m2 (max. 2 mg) i.v. day 1 and prednisone 100mg/m2/day orally days 1–5) was initiated in untreated patients with advanced centrocytic or advanced centroblastic-centrocytic lymphomas. Patients with no progression during treatment, received six or eight courses of PmM or COP depending on the response to therapy. Patients who had at least a reduction of the lymphoma mass of more than 50% during the first six courses, were considered as responders and were subsequently randomized for IFN-α maintenance versus observation only. The study was monitored by a onesided sequential test with a working significance level of 0.05. Based on an estimated rate of 65% remissions after COP the test was designed to detect an improvement of 20% by PmM with a probability of 90%. In October of 1993 a decision was stated by this sequential procedure. At that time 140 randomized patients, 74 treated with COP and 66 treated with PmM, were evaluable. Both regimens achieved comparable response rates of 84.8% with PmM and 82.4% with COP. So there was no significant improvement by PmM compared with COP. Granulocytopenia was the most important side effect after both protocols and was observed after 235 (42%) of 554 PmM treatment cycles and after 181 (32%) of 564 COP treatment courses (p<0,0001). Severe infections were very rare however under both regimens. (2.2% after COP and 1.0% after PmM) These data indicate a high efficiency of PmM and COP in advanced low-grade lymphomas. Further data are needed to assess their impact on disease free and overall survival as well as to evaluate the impact of IFN-α maintenance on these parameters.

  • comparison of Prednimustine mitoxantrone pmm and cyclophosphamide vincristine prednisolone cop in patients with low grade non hodgkin lymphomas followed by interferon α maintenance
    1994
    Co-Authors: Michael Unterhalt, Peter Koch, Martina Nahler, R Herrmann, W Hiddemann
    Abstract:

    The prognosis of patients with low-grade malignant non-Hodgkin lymphomas (NHL) in advanced stages III and IV has not significantly changed within the past 15 years [6,10]. The median survival after diagnosis is 6–10 years. While patients in stages I and II, in isolated cases also in stage III, can be cured by radiotherapy [11], only palliative treatment concepts are available for patients with advanced disease. New aspects recently emerged from a report by Landys et al. in 1988 [9], who reported on a high anti-lymphoma activity of the combination of prednismustine and mitoxantrone (PmM) with a low incidence of therapy associated side effects. In addition several groups have demonstrated a significant anti-lymphoma activity of interferon α (IFN α), even in patients resistant to conventional cytostatic therapy [1,3, 10, 13].

  • Prednimustine and mitoxantrone pmm in patients with low grade malignant non hodgkin s lymphoma nhl chronic lymphocytic leukemia cll and prolymphocytic leukemia pll
    Annals of Hematology, 1992
    Co-Authors: M Freund, S Wunschzeddies, M Schafers, J Wysk, I Seidel, W Hiddemann, A Hanauske, H Link, Hansjoachim Schmoll, Hubert Poliwoda
    Abstract:

    Thirty-five patients with a mean age of 60.6 years (44–78 years, 22 male, 13 female) with advanced low-grade non-Hodgkin's lymphoma (NHL), chronic lymphocytic leukemia (CLL), or prolymphocytic leukemia (PLL) were treated every 4 weeks with Prednimustine 100 mg/m2 p.o. d 1-d 5 and mitoxantrone 8 mg/m2 i.v. d 1 and d 2. Seven patients had CLL, one lymphocytic NHL, two PLL, 13 immunocytoma, nine centroblastic/ centrocytic NHL, and three centrocytic NHL. Twentyfive patients were pretreated. The subjective toxicity of the treatment was mild, with no WHO grade-3 alopecia, polyneuropathy, cardiotoxicity, mucositis, nausea, or vomiting. Hematologic side effects with WHO grade-4 granulopenia and thrombopenia were experienced by 26% and 23% of the patients, respectively. The overall response rate (CR + PR) was 72% for lymphoma patients and 37% for CLL patients, with a median remission duration of 14.6 months. The maximum response was achieved after a median of two treatment courses. Prednimustine with mitoxantrone is a subjectively well tolerated treatment for low-grade malignant NHL, to be further evaluated in phase-III studies. The regimen may shorten the duration of treatment, saving time-consuming outpatient visits and costs.

  • treatment of low malignant non hodgkin s lymphoma by cytoreductive chemotherapy with Prednimustine mitoxantrone pmm followed by interferon α2b maintenance
    1992
    Co-Authors: Michael Unterhalt, Peter Koch, Martina Nahler, R Herrmann, W Hiddemann
    Abstract:

    The prognosis of patients with low-grade malignant non-Hodgkin’s lymphomas in advanced stages III and IV has not significantly changed within the past 15 years. The median survival after diagnosis is 6–10 years [2,6,10].While patients in stages I and II, in some cases also in stage III, can be cured by radiotherapy [9], only palliative treatment concepts are available for patients with advanced disease. Although low-grade non-Hodgkin’s lymphomas respond to different forms of cytostatic therapy in the vast majority, a significant prolongation of survival has not been demonstrated. In 1988, Landys et al. [7] reported on a high anti-lymphoma activity of the combination of prednismustine and mitoxantrone with a low incidence of therapy-associated side effects.

H Yosef - One of the best experts on this subject based on the ideXlab platform.

  • Prednimustine sterecyt versus cyclophosphamide both in combination with methotrexate and 5 fluorouracil in the treatment of advanced breast cancer
    European Journal of Cancer, 1993
    Co-Authors: H Yosef, A Slater, C W Keen, J S Bunting, H Hopestone, H Parmar, J T Roberts, B Termander, B Nilsson
    Abstract:

    153 women with advanced breast cancer were randomly allocated for treatment with SMF [Prednimustine (Sterecyt) + methotrexate + 5-fluorouracil, 83 patients] or CMF (cyclophosphamide + methotrexate + 5-fluorouracil, 70 patients). Prednimustine was administered orally 100 mg/m 2 daily, for 5 days, and cyclophosphamide was administered orally 100 mg/m 2 , for 14 days, each, every 4 weeks. Methotrexate was given at a dose of 40 mg/m 2 and 5-fluorouracil at 600 mg/m 2 on day 1 and 8, every 4 weeks. Leucovorin was used in 39 patients to alleviate mucositis. The two treatment groups were balanced in terms of age, performance status, lymph node status, histology, menopausal status and previous therapy. Response was evaluated in 140 patients. Of 76 patients treated with SMF, 4 had a complete and 21 a partial response (CR + PR = 33%), 40 had no change (NC) and 11 had progressive disease (PD). Of 64 patients treated with CMF, 3 had a complete and 18 a partial response (CR + PR = 33%), 30 had no change (NC) and 13 had progressive disease (PD). Time to treatment failure and survival were similar in both groups. A relationship between haematological and gastrointestinal toxicity and therapeutic efficacy was demonstrated with a superior survival and response rate recorded for patients with such toxicity than in patients without. Haematological toxicity was, in general, mild to moderate with no difference between the two groups. Alopecia ( P = 0.008), nausea/vomiting ( P = 0.02) and euphoria ( P = 0.03) were more common in the CMF-treated group. Diarrhoea was more common in the SMF group ( P = 0.03). In conclusion, SMF seems to be as efficient as CMF with regard to response rate, time to treatment failure and survival. However, SMF was tolerated better than CMF.

Peter Lechner - One of the best experts on this subject based on the ideXlab platform.

  • Prednimustine combined with mitoxantrone and 5 fluorouracil for first and second line chemotherapy in advanced breast cancer
    Cancer Chemotherapy and Pharmacology, 1991
    Co-Authors: Hellmut Samonigg, Herbert Stoger, A K Kasparek, Marianne Schmid, Johann Dusleag, Karl P Pfeiffer, M G Smola, P Steindorfer, Peter Lechner
    Abstract:

    A total of 60 patients with advanced breast cancer were treated with a combination of Prednimustine (P: 110 mg/m2, days 1–5), mitoxantrone (M: 12 mg/m2, day 1) and 5-fluorouracil (F: 500 mg/m2, day 1) (PMF). Treatment was repeated every 3 weeks. In all 53 patients were evaluable for response. A total of 12 subjects had failed prior chemotherapy for metastatic disease. In response to PMF treatment we observed 21 partial remissions and 3 complete remissions, amounting to a total response rate of 45%. The median duration of response was 39 weeks, and median survival was 56 weeks. Doselimiting side effects were leukopenia (40 cases) and thrombocytopenia (11 patients). Nausea and vomiting was experienced by 93% of subjects; in 56% of cases it reached WHO stage II–III. Alopecia occured in 18% of our patients. Our results suggest that PMF represents an active regimen in the treatment of advanced breast cancer and yields a response rate of 45%. Considering that the majority of our patients had not received prior chemotherapy, the question remains open as to whether a 45% response rate outweighs the observed toxicity.