Leukeran

LEUKERAN (chlorambucil) is indicated in the treatment of chronic lymphatic (lymphocytic) leukemia, malignant lymphomas including lymphosarcoma, giant follicular lymphoma, and Hodgkin’s disease. It is not curative in any of these disorders but may produce clinically useful palliation.

Chlorambucil should not be used in patients whose disease has demonstrated a prior resistance to the agent. Patients who have demonstrated hypersensitivity to chlorambucil should not be given the drug. There may be cross-hypersensitivity (skin rash) between chlorambucil and other alkylating agents.

Because of its carcinogenic properties, chlorambucil should not be given to patients with conditions other than chronic lymphatic leukemia or malignant lymphomas. Convulsions, infertility, leukemia, and secondary malignancies have been observed when chlorambucil was employed in the therapy of malignant and non-malignant diseases. There are many reports of acute leukemia arising in patients with both malignant and non-malignant diseases following chlorambucil treatment.

In many instances, these patients also received other chemotherapeutic agents or some form of radiation therapy. The quantitation of the risk of chlorambucil-induction of leukemia or carcinoma in humans is not possible. Evaluation of published reports of leukemia developing in patients who have received chlorambucil (and other alkylating agents) suggests that the risk of leukemogenesis increases with both chronicity of treatment and large cumulative doses.

However, it has proved impossible to define a cumulative dose below which there is no risk of the induction of secondary malignancy. The potential benefits from chlorambucil therapy must be weighed on an individual basis against the possible risk of the induction of a secondary malignancy. Chlorambucil has been shown to cause chromatid or chromosome damage in humans. Both reversible and permanent sterility have been observed in both sexes receiving chlorambucil.

A high incidence of sterility has been documented when chlorambucil is administered to prepubertal and pubertal males. Prolonged or permanent azoospermia has also been observed in adult males. While most reports of gonadal dysfunction secondary to chlorambucil have related to males, the induction of amenorrhea in females with alkylating agents is well documented and chlorambucil is capable of producing amenorrhea. Autopsy studies of the ovaries from women with malignant lymphoma treated with combination chemotherapy including chlorambucil have shown varying degrees of fibrosis, vasculitis, and depletion of primordial follicles.