PubMed · 265134
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L H Einhorn. 1977. Cancer chemotherapy.. https://pubmed.ncbi.nlm.nih.gov/265134/
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The kinetics and mechanism of hydrolysis of the cytotoxic drug chlorambucil were investigated. A study of the reaction order and of the pH, dielectric constant, and ionic strength effects on the reaction rate revealed that the hydrolysis was a limiting unimolecular nucleophilic substitution, the rate-determining step being the ionization of the first 2-chloroethylamine chlorine. The hydrolysis rate was markedly dependent on the protonation degree of the chlorambucil basic group. indicating that a cyclic ethyleneimmonium ion may be involved in the rate-determining step.
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.