A phase III trial comparing prednimustine (LEO 1031) to chlorambucil plus prednisolone in advanced breast cancer

Abstract

Prednimustine is an ester of chlorambucil and prednisolone. The drug has had some activity in experimental as well as in human tumors, including breast cancer. The objective of the current study is to compare the clinical effectiveness and toxicity of prednimustine with its components of chlorambucil plus prednisolone, and to compare the clinical effectiveness and toxicity of a continuous treatment with an intermittent one. Two hundred and one patients with advanced breast cancer were randomized to the following treatments: I: prednimustine continuously; 40 mg/m2 d; II: prednimustine intermittently, 160 mg/m2 d 1 to 5, repeated every three weeks; and III: chlorambucil 8 mg/m2 d plus prednisolone 8 mg/m2 d, both given continuously. All treatments were given orally. One hundred and ninety five patients were evaluable for assessment of response to the treatments. The response rates were 21% in both of the prednimustine‐treated groups, whereas only 11% of the patients treated with chlorambucil and prednisolone responded. The duration of remission with continuous prednimustine was longer than with the other two treatment groups, but not significantly so. One hundred and ninety five patients were evaluable for assessment of hematologic toxicity. No differences were observed between the two prednimustine‐treated groups, whereas the group treated with chlorambucil plus prednisolone experienced a significantly higher degree of leukopenia and/or thrombopenia. Subjective toxicities, nausea, vomiting and psychical symptoms were only moderate in the three treatment groups, but significantly more pronounced in the group treated with intermittent prednimustine. Because of these promising results, prednimustine should be compared to other alkylating agents in patients with advanced breast cancer in randomized trials.

The clinical pharmacology of chlorambucil and prednimustine [letter]

“…Finally, Plym Forshell and colleagues (1983) state that in one study prednimustine was superior to a combination of chlorambucil plus prednisolone, both in terms of greater efficacy and reduced toxicity (Lober et al, 1983). We are unable to comment on this interesting observation as these data have not been published.…”

To determine the cytotoxicity of chlorambucil and one of its nitro-derivatives, conjugated to prasterone and pregnenolone, towards eight human cancer cell-lines

“…13 C NMR spectra were recorded using the listed NMR spectrometers at 125.77, 90.55 and 75.47 MHz, respectively. Mass spectra were recorded on a VG ZAB 2SE high resolution mass spectrometer, with Opus V3.1 and DEC 3000 Alpha Station and microanalysis were recorded on a LEEMANS C E440 Elemental Analyzer.…”

New Cytotoxic Drugs in Treatment of Breast Cancer

“…Response to prednimustine is significantly higher in patients without prior chemotherapy (41 %) compared to patients with prior chemotherapy (17%) (44). Side effects of prednimustine are moderate which has been the rational for combining that drug with other drugs, known to be associated with limited toxicity and thus to obtain combinations less toxic than those usually applied.…”