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At least 19 recordsLinked to original sources
PubMed1979

The use of estramustine and prednimustine versus prednimustine alone in advanced metastatic prostatic cancer patients who have received prior irradiation.

Estramustine has been shown previously to be an effective drug in the treatment of metastatic prostatic cancer, demonstrating significant objective and subjective responses in long-term non-randomized trials and in other randomized trials. In this study prednimustine alone has shown a minimal over-all objective response rate of 12.9% of the cases, although with marked subjective improvement of pain relief and patient performance status. The combination of prednimustine with estramustine did not result in improvement of objective or subjective response parameters. The effects in terms of responses or in terms of toxicity for either agent were not additive when they were given in combination. Cross-over for those patients whose disease progressed on prednimustine therapy to estramustine had some benefit in over-all survival. Prednimustine alone or in combination with estramustine may be used safely and could improve markedly the quality of life for irradiated patients with advanced prostatic cancer who failed on hormonal treatment and have too poor a bone marrow reserve to be treated by other currently available myelosuppressive agents.

Chlorambucil↗
PubMed1978

The use of estramustine and prednimustine versus prednimustine alone in advanced metastatic prostatic cancer patients who have received prior irradiation.

Estramustine has been shown previously to be an effective drug in the treatment of metastatic prostatic cancer, demonstrating significant objective and subjective responses in long-term non-randomized trials and in other randomized trials. In this study prednimustine alone has shown a minimal over-all objective response rate of 12.9 percent of the cases, although with marked subjective improvement of pain relief and patient performance status. The combination of prednimustine with estramustine did not result in improvement of objective or subjective response parameters. The effects in terms of responses or in terms of toxicity for either agent were not additive when they were given in combination. Cross-over for those patients whose disease progressed on prednimustine therapy to estramustine had some benefit in over-all survival. Prednimustine alone or in combination with estramustine may be used safely and could improve markedly the quality of life for irradiated patients with advanced prostatic cancer who failed on hormonal treatment and have too poor a bone marrow reserve to be treated by other currently available myelosuppressive agents.

Drug Therapy, Combination↗
PubMed1991

A pharmacokinetic study of prednimustine as compared with prednisolone plus chlorambucil in cancer patients.

The pharmacokinetic characteristics of prednisolone and of chlorambucil and its beta-oxidized metabolite, phenylacetic mustard (PAM) were studied in plasma after the oral administration of 200 mg prednimustine (Sterecyt) and a regimen consisting of 20 mg prednisolone plus 20 mg chlorambucil, respectively. A total of 12 cancer patients completed this trial. The drugs were given in a cross-over study as single doses, and serial plasma samples were collected for 32 h. Chlorambucil and PAM were assayed by a gas chromatographic/mass spectrometry method and prednisolone, by radioimmunoassay. The median relative availability of the prednisolone and chlorambucil moiety in prednimustine was 19% and 16%, respectively. Prednisolone, as well as chlorambucil and PAM, appeared later and at a significantly lower concentration in plasma after treatment with prednimustine as compared with the mixture of chlorambucil and prednisolone. We also found that the elimination phase of chlorambucil and PAM in plasma is prolonged after the administration of prednimustine as compared with chlorambucil per se. In contrast, the elimination of the prednisolone moiety of prednimustine and that following the administration of a plain prednisolone tablet did not seem to differ. The modified plasma profile of the alkylating components following prednimustine administration may be important for the clinical efficacy of prednimustine.

Adult↗
PubMed1978

Mammary tumour inhibition and subacute toxicity in rats of prednimustine and of its molecular components chlorambucil and prednisolone.

Prednimustine, a chlorambucil ester of pregnisolone, retarded growth of DMBA-induced mammary tumours in rats and reduced the number of tumours. A combination of chlorambucil and prednisolone (C + P) in the same proportion as in prednimustine, had similar effects, 8 and 26 mg per kg of the C + P combination being equipotnet to 16 and 64 mg per kg of prednimustine, respectively. The mortality figures suggested that prednimustine was considerably less toxic than equipotent doses of C + P. This toxicity difference was confirmed in a parallel investigation of the subacute toxicity in rats of prednimustine and C + P. This study showed that the mortality, reduction of lymphocytes and platelets, and bone marrow depression was much lower after pregnimustine than after equimolar amounts of the C + P combination. The results suggest that the low toxicity of prednimustine makes this drug a better cytostatic agent than the C + P combination treatment.

Animals↗
PubMed1989

Randomised trial comparing prednimustine with combination chemotherapy in advanced ovarian carcinoma.

A total of 76 patients with advanced epithelial ovarian carcinoma were randomised to receive 6 months of treatment with either a combination of hexamethylmelamine, 5-fluorouracil, cisplatin and prednimustine or prednimustine alone following initial surgery. Pathologically confirmed response rates were 35% for combination chemotherapy and 28% for prednimustine, and the overall survival was identical for the two groups. Seven patients achieved a pathologically defined complete response, one of whom relapsed at 8 months; the others remain disease-free 18-36 months (median, 23 months) after presentation. The extent of initial surgery significantly affected the survival of patients receiving prednimustine but not of those receiving combination chemotherapy. Prednimustine can produce durable responses in advanced ovarian cancer using a schedule that results in negligible toxicity.

Altretamine↗
PubMed1989

Studies on the pharmacokinetics of chlorambucil and prednimustine in patients using a new high-performance liquid chromatographic assay.

Following the oral administration of either chlorambucil/prednisolone or prednimustine to patients, the plasma levels of free chlorambucil and phenylacetic acid mustard, the beta-oxidation product of chlorambucil, were measured using a new high-performance liquid chromatographic (HPLC) assay. This assay permitted the simultaneous detection of the analyzed compounds with a lower limit of detection of 30 ng/ml. The pharmacokinetics of chlorambucil and phenylacetic acid mustard were found to be entirely different when prednimustine was administered as opposed to its components chlorambucil and prednisolone together. After the ingestion of the conjugate, the plasma concentration-time curves of chlorambucil and phenylacetic acid mustard showed a "delayed" pattern compared with those obtained after the administration of the components. The mean area under the concentration-time curves (AUCs) of prednimustine-derived chlorambucil and phenylacetic acid mustard were 25% and 40%, respectively, of the areas obtained after a stoichiometrically equivalent dose of chlorambucil. Free plasma prednimustine could not be detected at any time. This different pharmacokinetic behavior might offer an explanation for the superior therapeutic effects of prednimustine demonstrated by clinical studies.

Chlorambucil↗
PubMed1977

Preliminary clinical study of prednimustine in lung cancer.

Prednimustine is a prednisolone ester of chlorambucil which has been found effective in a variety of tumors. Eleven patients with advanced carcinoma of the lung (5 adenocarcinoma, 3 squamous cell carcinoma, 2 small cell carcinoma and 1 large cell carcinoma) were treated at a dosage of 40 mg. per day. Nine had previously failed on combination chemotherapy. No objective responses were observed. Leukopenia or thrombocytopenia were found in 4 patients with nadirs of 2,000 WBC and 60,000 platelets. The lack of response may be a function of the inability of lung carcinoma to concentrate the drug as shown with radioactive labeled Prednimustine. The malignant cells may lose their glucocorticoid binding capacity normally present in the lung. Determination of glucocorticoid binding capacity or Prednimustine uptake might predict the effectiveness of Prednimustine in the treatment of tumor. Prednimustine was well tolerated and may be given safely in advanced malignancies. Further studies with high intermittent doses and selection of tumors with steroid binding properties are now in progress.

Adenocarcinoma↗
PubMed1979

Prednimustine in adult acute myeloid leukaemia.

In 23 patients with acute myeloid leukaemia (AML) and over the age of 64, four remissions (17%) were obtained with Prednimustine as a single drug. The daily dose was 24--60 mg orally. In 14 patients aged between 35 and 64 years who were treated with Prednimustine 60--80 mg daily and vincristine 2.25 mg i.v. every 7--10 days, six remissions were obtained (43%). Upon remission, patients were given ,0--40 mg of Prednimustine daily as maintenance therapy. Drug-induced pancytopenia preceding remission was not recorded in any patient. There were no side effects of major importance during maintenance therapy, and the median duration of remission was 8 months. It is concluded that the low toxicity of Prednimustine in normal bone marrow cells is of value, especially in elderly patients with AML.

Adult↗
PubMed1991

Comparative pharmacokinetics of chlorambucil and prednimustine after oral administration.

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.

Administration, Oral↗
PubMed1986

Prednimustine in advanced breast cancer: a review.

This review summarizes the available data of phase II and phase III single-agent trials with predminustine and one phase II trial of prednimustine in combination with methotrexate, 5-fluorouracil, and tamoxifen in the treatment of advanced breast cancer. The data available so far indicate that the drug is more active than in combined treatment with the two components, chlorambucil and prednisolone. Future trials should be designed to analyze whether this could be ascribed to a sustained release of the components from the parent drug. The data also indicate that prednimustine is as active but less toxic than cyclophosphamide, but this needs to be confirmed in ongoing randomized comparisons. A number of phase II and phase III trials with prednimustine as a part of combinations are in progress. Mature results from these studies are needed to define the future role of prednimustine in the systemic therapy of breast cancer.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1990

High risk of therapy-related leukemia and preleukemia after therapy with prednimustine, methotrexate, 5-fluorouracil, mitoxantrone, and tamoxifen for advanced breast cancer.

Therapy-related acute non-lymphocytic leukemia or preleukemia was observed in five of 71 patients with advanced breast cancer treated with combination chemotherapy comprising prednimustine, methotrexate, 5-fluorouracil, mitoxantrone, and tamoxifen. In this closely followed cohort of patients the cumulative risk of leukemic complications was 25.4% +/- 10.3% (+/- SE) 37 months after start of chemotherapy. The relative risk of overt leukemia was 339 (95% CI: 41-1223), as two cases were observed versus 0.0059 cases expected. The very high risk of leukemia and preleukemia observed may partly reflect the advanced age of the patients (mean, 61 years) and partly the diagnostic procedures used, which included cytogenetic screening of all patients developing refractory cytopenia. A particularly high leukemogenic effect of prednimustine or a synergism between prednimustine and other drugs used in this study cannot be excluded. In the light of the above results, the authors caution against the use of intensive combination chemotherapy with alkylating agents as in the current study in potentially curable patients with breast cancer.

Adult↗
PubMed1991

Mitozantrone and prednimustine in the treatment of advanced breast cancer--a toxic regimen with low activity.

The combination of mitozantrone and prednimustine has been reported to elicit response rates of around 50% in patients with advanced breast cancer. In the present trial, either three or nine courses of this combination were given to previously untreated patients with advanced breast cancer. Mitozantrone was given at 12 mg/m2 on day 1 and prednimustine was given orally at 130 mg/m2 on days 1-5; treatment was repeated every 4 weeks. A total of 34 patients were treated; the performance status was 0-1 in 29 subjects and 2 in 5 cases. Locoregional disease only was present in 13 patients; 9 showed lung involvement; 8, liver; 3, bone; and 1, stomach involvement. A total of 10 subjects had received no prior hormone therapy. The median disease-free interval from the time of initial diagnosis was 24 months (range, 0-144 months). In all 14/23 patients exhibited an oestrogen receptor level of greater than 20 fmol. Grade 1 nausea and vomiting occurred in 16 patients and that of grade 2-3, in 11 subjects; nausea was prolonged for greater than 10 days in 7 cases. Grade 4 neutropenia occurred in 2 patients. The response rate was 21% (95% confidence interval, 8%-38%). The combination of mitozantrone and oral prednimustine is toxic and displays low activity.

Adult↗
PubMed1992

Prednimustin treatment in primary biliary cirrhosis: a preliminary study.

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.

Aged↗
PubMed1989

Prednimustine treatment in malignant lymphomas.

Prednimustine (Stereocyt, Leo 1031) is a chlorambucil ester of prednisolone. Results from clinical trials confirm that prednimustine is active in malignant lymphomas. The efficacy of Stereocyt was evaluated in 25 patients, who were divided into three subgroups: 10 patients with refractory Hodgkin's disease and 7 with refractory non-Hodgkin lymphoma (NHL), while 8 patients received prednimustine as primary therapy for low-grade NHL. Totally 17 partial remissions were observed in all three groups of patients. Leukopenia and thrombopenia were induced in 3 patients, but were mild and reversible after withdrawal of the drug.

Adult↗
PubMed1985

Value of prednimustine in treating non Hodgkin's lymphomas of favourable histological type.

24 patients with non-Hodgkin's lymphomas of low-grade malignancy (stage III and IV) were treated either with a single drug (prednimustine) or with combination chemotherapy (cyclophosphamide, vincristine and prednisone). Response to therapy was similar in both groups. Prednimustine induced complete remission in 6 from 13 patients, while in that group treated with combination chemotherapy a complete remission was recorded in 4 from 11 patients. Both regimens were well tolerated. Therapy with prednimustin has an advantage in oral administration enabling it to be used in out-patient practice.

Adult↗
PubMed1977

Combined therapy of advanced prostatic carcinoma with estramustine and prednimustine.

We treated 21 patients with stage D prostatic adenocarcinoma who had had unsuccessful hormonal therapy with a combination of 600 mg. per M.2 per day estramustine phosphate (Estracyt) and 15 mg. per M.2 per day prednimustine (Stereocyt, Leo 1031) in daily oral doses. Estramustine is a combination of estradiol and nitrogen mustard, and alone has shown objective responses in advanced prostatic cancer. Prednimustine is an ester of chlorambucil and prednisone. The preliminary results (after 2 to 9 months of therapy) show 5 patients (24 per cent) did not benefit from the drug and 7 patients (33 per cent) are stable. These preliminary results indicate the possible advantage of adding an alkylating agent (prednimustine) to estramustine in advanced prostatic carcinoma. Currently, a national randomized trial by the National Prostatic Cancer Project is evaluating this therapeutic innovation.

Aged↗
PubMed1992

Assembly of prednimustine low-density-lipoprotein complexes and their cytotoxic activity in tissue culture.

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.

3T3 Cells↗
PubMed1992

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.

Adult↗