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Phase II trial of Prednimustine. Leo-1031 (NSC-134087) in acute non-lymphocytic leukemia.

18 patients with acute non-lymphocytic leukaemia were treated with Prednimustine, a chlorambucil ester of prednisolone, as a single drug. 5 patients responded with falling blast counts in peripheral blood, but only 1 obtained a complete remission of 3 months' duration. Since the activity of Prednimustine is lower than that of other commonly used drugs in acute non-lymphocytic leukaemia, future studies should concentrate on other aspects, such as treatment of patients with steroid receptor-positive blast cells or other types of leukaemia.

Adult

[Effect of Prednimustine (Leo 1031) in chronic lymphatic leukemia].

46 ambulatory patients with chronic lymphocytic leukemia were treated with Prednimustine either continuously (daily or each other day 20 mg) or intermittently (daily 20 mg for 14 days, followed by a pause of 4 weeks). A good response was seen in 28 patients lasting up to 17 + months (mean 4,5 + months) after terminating therapy. Patients without prior chemotherapy have improved earlier and to a smaller amount of the total dose applicated. Signes of bone marrow toxicity (anaemia, thrombocytopenia) were observed in 8 cases, gastrointestinal side effects in 7 cases, cutaneous exanthema in 3 cases, and one patient exhibited a severe stomatitis after treatment. Prednimustine constitutes an effective drug for chronic lymphatic leukemia.

Adult

Prednimustine combined with mitoxantrone and 5-fluorouracil for first and second-line chemotherapy in advanced breast cancer.

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. Dose-limiting 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 occurred 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.

Adult

Cellular kinetics of prednimustine versus chlorambucil plus prednisolone in vitro.

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.

Animals

Remission induction with carboplatin-epirubicin-prednimustine followed by consolidation radiotherapy in advanced ovarian cancer.

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.

Antineoplastic Combined Chemotherapy Protocols

[Treatment of aggressive non-Hodgkin's lymphoma in aged patients with a combination of methyl-GAG, etoposide and prednimustine].

The authors report the results of a chemotherapy regimen of methyl-GAG, etoposide and prednimustine in 21 elderly patients (median age = 78 years) with aggressive non-Hodgkin's lymphoma. Sixteen patients responded (11 complete remissions, 5 partial remissions) with minor toxic side-effects. This regimen could be proposed for patients whose age and/or cardiovascular status prohibit treatment with usual anthracycline-containing chemotherapy programs.

Aged

CCNU, etoposide, and prednimustine (CEP) in refractory Hodgkin's disease.

Starting in February 1980, 58 patients with Hodgkin's disease refractory to both MOPP and ABVD received as third-line chemotherapy a combination of CCNU or lomustine, etoposide, and prednimustine (CEP). Complete response (CR) was achieved in 40% of cases and partial response (PR) in 14%. The median duration of CR was greater than 15 months, and the median survival of complete responders was longer than 24 months. In addition, CEP alternating with ABVD was given to 21 patients refractory to MOPP chemotherapy. In this series, CR was documented in 67% of patients with a median duration of 24+ months and a median survival of 36+ months. Treatment was generally well tolerated, and all acute side effects were reversible. Present findings indicate that CEP is an effective regimen in patients refractory to MOPP and ABVD.

Antineoplastic Combined Chemotherapy Protocols

Advanced mycosis fungoides: chemotherapy with etoposide, methotrexate, bleomycin, and prednimustine.

We assessed the efficacy and toxicity of a chemotherapeutic regimen in patients with stage II-IV mycosis fungoides. Eleven previously treated outpatients received etoposide and methotrexate p.o. and bleomycin i.v. every 3 weeks. There was 1 complete remission for 2 months and 7 partial remissions with a median duration of 6 months (range 2-16 months). Three patients showed stable disease lasting 1-5 months (median 2 months). In 4 patients, remissions were maintained with prednimustine after 10 courses of induction chemotherapy. Mild nausea occurred in all patients and severe leukocytopenia and thrombocytopenia in 1 patient. Toxicity of the treatment regimen was acceptable and response rates comparable to those seen by others with more toxic single-agent or combination chemotherapies.

Adult

Prednimustine (NSC-134087, Leo 1031) treatment of lymphocytic and lymphocytic-histiocytic lymphomas.

Nineteen patients with advanced lymphocytic or lymphocytic-histiocytic lymphomas were treated with Prednimustine (NSC-134087, Leo 1031). The median induction dose was 25 mg/m2 a day by mouth (range 11-42). Ten patients had previously received radiation or chemotherapy, or both. Four patients had a complete remission and eleven a partial remission. The median duration of remission was 12.5+ months for complete responders and 5 months for partial responders. Thirteen patients had a moderate myelosuppression. One patient had urticaria and pruritus and refused further treatment.

Bone Marrow

Prednimustine therapy for advanced prostatic cancer.

23 patients with advanced, hormonal-resistant, prostatic cancer were treated with daily oral prednimustine--a combination of prednisolone and chlorambucil. 8 patients (35%) subjectively responded with disappearance of skeletal pain and improvement in appetite, weight and sense of well being. 3 patients had objective evidence of tumour regression. Clinical toxicity was moderate, and only occasional myelosuppression was encountered. The ease of administration and predictable toxicity of prenimustine make it a potentially useful agent, alone or in combination, for advanced prostatic cancer.

Adrenal Glands

Continuous treatment of non-Hodgkin's malignant lymphoma with prednimustine (Leo 1031).

The effect of Prednimustine was evaluated in 37 patients with generalised non-Hodgkin's lymphomas. The patients were divided into three groups according to dosage and previous treatment. Totally, in all three groups, 22 complete and 10 partial remissions were observed. During follow-up, five of the complete responders and all partial responders have relapsed. Leucopenia and thrombocytopenia were induced in several patients, but were always moderate and reversible after withdrawal of the drug. In some patients with a history of peptic ulcer or diabetes mellitus, these conditions were aggravated.

Adult

Treatment of resistant Hodgkin's disease with CCNU, etoposide and prednimustine (CEP).

Starting in January 1984, 63 patients with resistant Hodgkin's disease received CEP as salvage-usually third-line-chemotherapy. Complete response (CR) was achieved in 3%, partial response (PR) in 51%. The median duration of remission (CR + PR) was greater than 15 months. Treatment was generally well tolerated. Our results confirm that CEP is an effective therapeutic regimen in resistant Hodgkin's disease.

Adolescent

Prednimustine.

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Animals