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Medical Oncology and Tumor... 1993Seventy-eight patients with advanced non-Hodgkin's lymphomas were randomized for treatment with prednimustine (Sterecyt) in two different schedules: either receiving... (Clinical Trial)
Clinical Trial Comparative Study Randomized Controlled Trial
Seventy-eight patients with advanced non-Hodgkin's lymphomas were randomized for treatment with prednimustine (Sterecyt) in two different schedules: either receiving continuous treatment at a dosage of 60 mg daily, or intermittent two-week courses with 200 mg daily for five days. The aim of the study was to compare efficacy and side effects of the two different schedules. Forty patients received continuous, and 38 patients intermittent treatment. Objective response was achieved in 66% of 71 evaluable patients, equally distributed between the two treatment arms. The 10-year survival rate was 20% (SE = 6%; continuous treatment) and 11% (SE = 5%; intermittent treatment), respectively (logrank p = 0.26). Median time to response, duration of response and time to progression showed no significant difference between the treatment groups. Median time on treatment was longer for patients treated continuously, probably due to more easily performed dose adjustments in such patients. There was a significant decrease of the white blood cell counts in patients who received prednimustine continuously compared with those treated according to the intermittent schedule (p = 0.02). No significant differences were found regarding the thrombocyte levels. The response rate was closely related to haematological toxicity (p = 0.01). Our results suggest that prednimustine in non-Hodgkin's lymphomas has similar effectiveness both in daily treatment and in a two-weekly intermittent schedule. Continuously given treatment may be easier to govern and, thereby, allow for higher treatment intensity. With respect to toxicity, daily doses of approximately 30-40 mg in previously untreated patients may be recommended.
Topics: Adult; Aged; Aged, 80 and over; Dose-Response Relationship, Drug; Drug Administration Schedule; Female; Humans; Lymphoma, Non-Hodgkin; Male; Middle Aged; Prednimustine
PubMed: 8164452
DOI: 10.1007/BF02989664 -
Hematological Oncology 1992Forty-five patients with low grade non-Hodgkin's lymphomas were studied with respect to the fraction of S-phase cells in fresh tumour material by flow cytometric...
Forty-five patients with low grade non-Hodgkin's lymphomas were studied with respect to the fraction of S-phase cells in fresh tumour material by flow cytometric analysis. Patients with stage I lymphomas were treated with radiotherapy, patients with stage II-IV lymphomas with Prednimustine (Sterecyt). Patients with lymphocytic lymphomas of CLL type were only treated if they had symptoms. Median S-phase fraction in the samples was 2.0 per cent. A significantly shorter survival was found for patients with lymphocytic lymphomas with S-phase fractions > 2.0 per cent compared with cases showing lower S-phase fractions. No significant difference in survival was found in the subgroups of immunocytic or follicular and follicular/diffuse centroblastic/centrocytic lymphomas. In a Cox multivariate analysis, in which also age, constitutional symptoms, stage and morphology were included, the fraction of S-phase cells was found to be a statistically significant, prognostic parameter for low grade lymphomas, mainly due to the result in the subgroup of lymphocytic lymphomas.
Topics: Cell Cycle; Cell Division; Cell Separation; Flow Cytometry; Humans; L-Lactate Dehydrogenase; Lymphoma, Non-Hodgkin; Middle Aged; Multivariate Analysis; Prognosis; S Phase; Thymidine Kinase
PubMed: 1398513
DOI: 10.1002/hon.2900100307 -
Journal of Clinical Oncology : Official... Feb 1992A prospective trial with a new combination of etoposide, mitoxantrone, and prednimustine (VMP), specifically devised for elderly patients with non-Hodgkin's lymphoma... (Clinical Trial)
Clinical Trial
PURPOSE
A prospective trial with a new combination of etoposide, mitoxantrone, and prednimustine (VMP), specifically devised for elderly patients with non-Hodgkin's lymphoma (NHL), was undertaken.
PATIENTS AND METHODS
Between January 1987 and April 1990, 52 consecutive unselected patients older than 70 years (median age, 75.6 years) with stage I to IV intermediate- and high-grade NHL, or with stage III to IV low-grade malignancy with symptomatic disease received etoposide and prednimustine 80 mg/m2 orally for 5 days and mitoxantrone 8 to 10 mg/m2 day 1 intravenously (IV), every 21 days. Fourteen patients were previously treated.
RESULTS
Among the 48 assessable patients, the objective response rate was 81%; 46% of the patients achieved a complete response (CR). The overall toxicity seemed to be acceptable, with 15 (7%) episodes of grade 4 leukopenia and 41 (18%) episodes of grade 3, over a total of 226 administered cycles. The median survival was 12 months. The patients who obtained CR have a longer survival than those who did not (34 v 8 months; P less than .001). Fifty-eight percent of patients achieving CR were free from relapse at 24 months; up to 36 months from the start of therapy, 25% were free from relapse. As far as patients affected by diffuse histiocytic lymphoma, 66% of previously untreated patients obtained a CR, and 55% of them were still disease-free at 24 months from the start of therapy.
CONCLUSION
We conclude that VMP is effective, well tolerated, and feasible on an outpatient basis in an unselected, elderly population affected by unfavorable NHL.
Topics: Age Factors; Aged; Aged, 80 and over; Ambulatory Care; Antineoplastic Combined Chemotherapy Protocols; Drug Evaluation; Etoposide; Female; Humans; Lymphoma, Non-Hodgkin; Male; Mitoxantrone; Prednimustine; Prognosis; Prospective Studies; Survival Analysis; Treatment Outcome
PubMed: 1732423
DOI: 10.1200/JCO.1992.10.2.228 -
Annals of Hematology Feb 1992Thirty-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...
Prednimustine and mitoxantrone (PmM) in patients with low-grade malignant non-Hodgkin's lymphoma (NHL), chronic lymphocytic leukemia (CLL), and prolymphocytic leukemia (PLL).
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. Twenty-five 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 out-patient visits and costs.
Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Female; Humans; Leukemia, Lymphocytic, Chronic, B-Cell; Leukemia, Promyelocytic, Acute; Lymphoma, Non-Hodgkin; Male; Middle Aged; Mitoxantrone; Prednimustine
PubMed: 1554799
DOI: 10.1007/BF01715350 -
Journal of Internal Medicine Feb 1992We observed a decrease in serum bilirubin, alkaline phosphatases (ALP) and IgM in five patients with primary biliary cirrhosis (PBC) treated with Prednimustin (Sterecyt)...
We observed a decrease in serum bilirubin, alkaline phosphatases (ALP) and IgM in five patients with primary biliary cirrhosis (PBC) treated with Prednimustin (Sterecyt) for 6 months. In contrast to pretreatment findings, C3 activation was undetectable during treatment in three patients where normalization of serum IgM was achieved. After discontinuation of Prednimustin, bilirubin and ALP levels rapidly returned to pretreatment values, although IgM remained normal for up to 6 months in some patients. We conclude that Prednimustin might be of value in patients with symptomatic PBC where liver transplantation is not an option, and that it should be evaluated in a controlled study. However, the rapid reactivation of the disease after conclusion of treatment must be considered.
Topics: Aged; Female; Humans; Immunoglobulin M; Liver Cirrhosis, Biliary; Liver Function Tests; Male; Middle Aged; Prednimustine
PubMed: 1541936
DOI: 10.1111/j.1365-2796.1992.tb00515.x -
Cancer Chemotherapy and Pharmacology 1992The lipophilic anticancer drug prednimustine was incorporated into model low-density-lipoprotein (m-LDL) using a novel modified method. The major steps of this procedure... (Comparative Study)
Comparative Study
The lipophilic anticancer drug prednimustine was incorporated into model low-density-lipoprotein (m-LDL) using a novel modified method. The major steps of this procedure involve the preparation of a microemulsion containing the drug and the complexing of this emulsion with apolipoprotein B (apo B) that has been delipidated by heptane extraction. The resulting particles contained on average 338 mol prednimustine/mol apoB and exhibited a diameter that was ca. 2.5 times that of native LDL. The cellular binding, uptake, and metabolism of the complexes were found to be similar to those of native LDL. The cytotoxic activity of the complexes was monitored in vitro against T-47D breast cancer cells and normal 3T3 fibroblasts. The activity of prednimustine in m-LDL against T-47D cells after 24 h treatment was nearly 50% higher than that of the free drug, whereas in 3T3 cells the difference was relatively small. The results indicate that it is possible to target drug/m-LDL complexes to cancer cells exhibiting high LDL-receptor activity.
Topics: 3T3 Cells; Animals; Apolipoproteins B; Cell Division; Cell Survival; Dose-Response Relationship, Drug; Drug Carriers; Emulsions; Humans; Lipoproteins, LDL; Mice; Prednimustine; Time Factors; Tumor Cells, Cultured
PubMed: 1733558
DOI: 10.1007/BF00686259 -
Cancer Chemotherapy and Pharmacology 1992Intracellular concentrations of prednimustine (PM), chlorambucil (CLB), phenylacetic acid mustard (PAAM) and prednisolone (P) were measured in different experimental... (Comparative Study)
Comparative Study
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.
Topics: Animals; Carcinoma; Chlorambucil; Chromatography, High Pressure Liquid; Colonic Neoplasms; Mammary Neoplasms, Experimental; Melanoma, Experimental; Nitrogen Mustard Compounds; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Prednimustine; Prednisolone; Rats; Time Factors; Tumor Cells, Cultured
PubMed: 1537076
DOI: 10.1007/BF00685948 -
International Journal of Clinical... 1992Adjuvant chemoradiotherapy was administered to 26 patients with stage Ic-IV ovarian cancer after radical cytoreductive surgery. All patients received six cycles of...
Adjuvant chemoradiotherapy was administered to 26 patients with stage Ic-IV ovarian cancer after radical cytoreductive surgery. All patients received six cycles of carboplatin, epirubicin, and prednimustine and had no clinical evidence of disease after completion of chemotherapy. They received whole-abdominal radiation and radiation to the retroperitoneal lymph nodes. This protocol was discontinued for five (23%) patients because of myelosuppression, progressive disease, or withdrawal. One patient had a small bowel obstruction due to intraperitoneal adhesions. The survival of ten stage-III ovarian cancer patients, who received chemoradiotherapy and were evaluable for assessment of treatment efficacy, was retrospectively compared with the survival of 11 stage-III patients who received chemotherapy only. At 36 months, a slight advantage of the chemoradiotherapy versus the chemotherapy-only group was observed (p = 0.11). These preliminary results suggest that adjuvant chemoradiotherapy may prolong the "no evidence of disease" interval of radically operated ovarian cancer patients. Toxicity is acceptable when second-look surgery is avoided and when subsequent radiotherapy is limited to patients with no evidence of disease.
Topics: Antineoplastic Combined Chemotherapy Protocols; Carboplatin; Chemotherapy, Adjuvant; Combined Modality Therapy; Epirubicin; Female; Humans; Lymphatic Irradiation; Ovarian Neoplasms; Prednimustine; Remission Induction
PubMed: 1297644
DOI: No ID Found -
Annals of Oncology : Official Journal... 199180 patients with advanced epithelial ovarian carcinoma were treated for 6 months with cisplatinum and prednimustine following initial surgery. Response to treatment was... (Clinical Trial)
Clinical Trial
80 patients with advanced epithelial ovarian carcinoma were treated for 6 months with cisplatinum and prednimustine following initial surgery. Response to treatment was assessed by second-look surgery. The objective response rate was 69% with 38% achieving a complete response for up to 55 months. The toxicity of this regimen was acceptable. Statistically, de-bulking or partial de-bulking had a significant beneficial effect on the likelihood of a complete response. The best survival figures were associated with maximum de-bulking. The combination of cisplatinum and prednimustine is a new and active regimen for operable advanced epithelial ovarian carcinoma.
Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Squamous Cell; Cisplatin; Drug Evaluation; Female; Follow-Up Studies; Humans; Middle Aged; Ovarian Neoplasms; Prednimustine
PubMed: 1801882
DOI: 10.1093/oxfordjournals.annonc.a057859 -
RoFo : Fortschritte Auf Dem Gebiete Der... Oct 1991
Topics: Adult; Antineoplastic Combined Chemotherapy Protocols; Bleomycin; Cyclophosphamide; Doxorubicin; Etoposide; Female; Glyoxal; Hodgkin Disease; Humans; Ifosfamide; Prednimustine; Prednisone; Procarbazine; Thymus Hyperplasia; Tomography, X-Ray Computed; Vinblastine; Vincristine
PubMed: 1718486
DOI: 10.1055/s-2008-1033281