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.
DOSAGE AND ADMINISTRATION
The usual oral dosage is 0.1 to 0.2 mg/kg body weight daily for 3 to 6 weeks
as required. This usually amounts to 4 to 10 mg per day for the average patient.
The entire daily dose may be given at one time. These dosages are for initiation
of therapy or for short courses of treatment. The dosage must be carefully adjusted
according to the response of the patient and must be reduced as soon as there
is an abrupt fall in the white blood cell count. Patients with Hodgkin's disease
usually require 0.2 mg/kg daily, whereas patients with other lymphomas or chronic
lymphocytic leukemia usually require only 0.1 mg/kg daily. When lymphocytic
infiltration of the bone marrow is present, or when the bone marrow is hypoplastic,
the daily dose should not exceed 0.1 mg/kg (about 6 mg for the average patient).
Alternate schedules for the treatment of chronic lymphocytic leukemia employing
intermittent, biweekly, or once-monthly pulse doses of chlorambucil have been
reported. Intermittent schedules of chlorambucil begin with an initial single
dose of 0.4 mg/kg. Doses are generally increased by 0.1 mg/kg until control
of lymphocytosis or toxicity is observed. Subsequent doses are modified to produce
mild hematologic toxicity. It is felt that the response rate of chronic lymphocytic
leukemia to the biweekly or once-monthly schedule of chlorambucil administration
is similar or better to that previously reported with daily administration and
that hematologic toxicity was less than or equal to that encountered in studies
using daily chlorambucil.
Radiation and cytotoxic drugs render the bone marrow more vulnerable to damage,
and chlorambucil should be used with particular caution within 4 weeks of a
full course of radiation therapy or chemotherapy. However, small doses of palliative
radiation over isolated foci remote from the bone marrow will not usually depress
the neutrophil and platelet count. In these cases chlorambucil may be given
in the customary dosage.
It is presently felt that short courses of treatment are safer than continuous
maintenance therapy, although both methods have been effective. It must be recognized
that continuous therapy may give the appearance of “maintenance”
in patients who are actually in remission and have no immediate need for further
drug. If maintenance dosage is used, it should not exceed 0.1 mg/kg daily and
may well be as low as 0.03 mg/kg daily. A typical maintenance dose is 2 mg to
4 mg daily, or less, depending on the status of the blood counts. It may, therefore,
be desirable to withdraw the drug after maximal control has been achieved, since
intermittent therapy reinstituted at time of relapse may be as effective as
Procedures for proper handling and disposal of anticancer drugs should be used.
Several guidelines on this subject have been published.1-8 There
is no general agreement that all of the procedures recommended in the guidelines
are necessary or appropriate.
Hepatic Impairment: Patients with hepatic impairment should be closely
monitored for toxicity. As chlorambucil is primarily metabolized in the liver,
dose reduction may be considered in patients with hepatic impairment when treated
with LEUKERAN. However, there are insufficient data in patients with hepatic
impairment to provide a specific dosing recommendation.
LEUKERAN is supplied as brown, film-coated, round, biconvex tablets containing
2 mg chlorambucil in amber glass bottles with child-resistant closures. One
side is engraved with “GX EG3” and the other side is engraved with
Bottle of 50 (NDC 0173-0635-35).
Store in a refrigerator, 2° to 8°C (36° to 46°F).
1. NIOSH Alert: Preventing occupational exposures to antineoplastic
and other hazardous drugs in healthcare settings. 2004. U.S. Department of Health
and Human Services, Public Health Service, Centers for Disease Control and Prevention,
National Institute for Occupational Safety and Health, DHHS (NIOSH) Publication
2. OSHA Technical Manual, TED 1-0.15A, Section VI: Chapter 2.
Controlling Occupational Exposure to Hazardous Drugs. OSHA, 1999. http://www.osha.gov/dts/osta/otm/otm_vi/otm_vi_2.html
3. American Society of Health-System Pharmacists. ASHP guidelines
on handling hazardous drugs. Am J Health-Syst Pharm. (2006) 63:1172-1193.
4. Polovich, M., White, J. M., & Kelleher, L.O. (eds.) 2005.
Chemotherapy and biotherapy guidelines and recommendations for practice (2nd.
ed.) Pittsburgh, PA: Oncology Nursing Society.
GlaxoSmithKline, Research Triangle Park, NC 27709.