Cancer chlorambucil

Davies, I.D., Allanson, J.P., and Causon, R.C. 1999. Rapid determination of the anti-cancer drug chlorambucil (Leukeran) and its phenyl acetic acid mustard metabolite in human serum and plasma by automated solid-phase extraction and liquid chromatography-tandem mass spectrometry. J. Chrom-matogr. B. 732 173. 

A. Bielawska, K. Bielawski, K. Chrzanowski, S. Wolczynski, Prolinase-Activated Prodrug for Cancer Chemotherapy. Cytotoxic Activity of Proline Analogue of Chlorambucil in Breast Cancer MCF-7 Cells , Farmaco 2000, 55, 736-741. 

Cytotoxic agents which are used both for the treatment of cancer as for their immunosuppressive activity include cyclophosphamide, methotrexate, chlorambucil, vincristine, vinblastine and dactinomycin. 

Chlorambucil is an anticancer chemotherapeutic agent, used in the treatment of lymphomas. The targeting of this drug to the lymphatic system may improve the treatment of lymphatic cancers. Hence, a prodrug of chlorambucil was synthesized, with the parent drug attached to the 2-position of a triglyceride with palmitic acid in the 1 and 3 positions (Figure 6.6). 

Bielawska, A., Bielawska, K., Chrzanowski, K., and Wolczynski, S. Prolidase-activated prodrug for cancer chemotherapy cytotoxic activity of praline analogue of chlorambucil in breast cancer MCF-7 cells. II Farmaco 55 736-741, 2000. 

Ghose, T. Norvell, S.T. Guclu, A. Bodurtha, A. Tai, J. MacDonald, A.S. Immunochemotherapy of malignant melanoma with chlorambucil-bound antimelanoma globulins preliminary results in patients with disseminated disease. J. Natl. Cancer Inst. 1977, 58, 845-852. 

Chlorambucil is an alkylating agent that retards or stops growth of cancer cells. It is used to treat chronic lymphocytic leukemia, malignant lymphomas such as lymphosarcoma, giant follicular lymphoma, ovarian cancer, and Hodgkin s disease. 

Chlorambucil is known to be a human carcinogen based on sufficient evidence of carcinogenicity in humans. Leukemia was reported in a number of epidemiological studies in which chlorambucil was used as a chemotherapeutic agent either alone or in combination with other agents. The risk of developing cancer increases with increasing dose and time of treatment. 

McLean A et al. Pharmacokinetics and metabolism of chlorambucil in patients with malignant disease. Cancer Treatment Reviews, 1979, 6, Suppl 33-42. 

Tai A, Blair AH, Ghosh T. Tumor inhibition by chlorambucil covalently linked to antitumor globulin. Eur J Cancer Qin Oncol 1979 15 1357-1363. 

Cyclophosphamide prodnces a similar response rate as chlorambucil (30% to 40%) and can be used in patients who have difficulty tolerating chlorambncU or in whom response is not optimal. Some patients refractory to chlorambucil will respond to cyclophosphamide. Cyclophosphamide is less commonly used because of its risk of hemorrhagic cystitis and bladder cancer with prolonged treatment. ... 

Significant improvements were achieved with the drugs chlorambucil (Leukeran, 1952) and melphalan (Alkeran, 1954), both developed at the Chester Beatty Laboratory in London. These drugs were more water-soluble (and hence available by mouth rather than intravenous infusion) and more easily taken up by cancer cells. They were also less toxic to bone-marrow cells and have been widely used over the intervening years for the treatment of various leukaemias and other tumours. An interesting combination of the female sex hormone oestradiol with mechlorethamine was invented in Romania in 1966, and was marketed under the trade-name Estracyte (estra-mustine) for the treatment of prostatic cancer. 

Cll. Ciaccio, P. J., Tew, K. D., and LaCreta, F. P., The spontaneous and glutathione S-transfer-ase-mediated reaction of chlorambucil with glutathione. Cancer Commun. 2, 279-285... 

H6. Hall, A., Robson, C. N., Hickson, I. D., Harris, A. L., Proctor, S. J., and Cattan, A. R., Possible role of inhibition of glutathione S-transferase in the partial reversal of chlorambucil resistance by indomethacin in a Chinese hamster ovary cell line. Cancer Res. 49, 6265-6268 (1989). 

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