Chlorambucil toxicity

The most commonly used dose for fludarabine is 20 mg/m2 intravenously daily for 5 consecutive days, whereas chlorambucil can be taken daily as an oral tablet with the dose ranging from 4 to 10 mg/day.21 Fludarabine is associated with more toxicities than chlorambucil, including myelosuppression and prolonged immunosuppression.19 Resulting infectious complications may occur during the periods of prolonged immunosuppression. The ease of administration and limited side effects make chlorambucil a practical option for symptomatic elderly patients who require palliative therapy... 

Owing to the favorable activity profile of 66, which acts as a prodrug of the active species 62, additional studies were conducted on 66 to establish its cell-based profile. It was determined that 66 potentiated chlorambucil (74) toxicity in cell lines expressing GST Pl-1, namely HT-29, HT4-1, SK OV-3, and SK VLB. Also, while 66 alone did not prevent tumor growth in the HT4-1 xenograph model, 66 increased by 56% the tumor growth inhibitory effect of melphalan (75). 

Despite the fact that alkylating agents exhibit a common mechanism of action, their clinical use varies depending on differences in pharmacokinetics, metabolism, hpid solubility, ability to penetrate membranes, and toxicity. They can be classified as nitrogen-containing mustard derivatives (mechorethamine, chlorambucil, melfalan, cyclophosphamide, ifos-famide), derivatives of ethylenimine (thiotepa), nitrosoureas (carmustine, lomustine, strep-tozocin), alkylsulfonates (busulfan), and derivatives of platinum (cwplatin, carboplatin). 

With chlorambucil and melphalan, although administered orally complaints of nausea and vomiting are minimal. The other toxic effects are comparable to those of cyclophosphamide. Chlorambucil has marked immunosuppressant activity. 

Bone marrow toxicity is the major side effect of chlorambucil. Nausea is uncommon or mUd, and hair loss does not occur. Chlorambucil shares the immunosuppressive, teratogenic, and carcinogenic properties of the nitrogen mustards. 

Chlorambucil Leukeran Chronic lymphocytic leukemia Hodgkin disease non-Hodgkin lymphomas Blood disorders (leukopenia, thrombocytopenia, anemia,] skin rashes/itching pulmonary toxicity seizures... 

Chlorambucil (Leukeran) is the least toxic nitrogen mustard, and is used as the drug of choice in the treatment of chronic lymphocytic leukemia. It is absorbed orally, is slow in its onset of action, and may cause bone marrow depression. 

CHLORAMBUCIL H2 RECEPTOR BLOCKERS -CIMETIDINE t adverse effects of alkylating agent, e.g. myelosuppression Additive toxicity Monitor more closely monitor FBC regularly... 

CIMETIDINE BUSULFAN, CARMUSTINE, CHLORAMBUCIL CYCLOPHOSPHAMIDE, ESTRAMUSTINE, IFOS-FAMIDE, LOMUSTINE, THIOTEPA, TREOSULFAN T adverse effects of cytotoxic, e.g. myelosuppression Additive toxicity. Possible minor inhibition of cyclophosphamide metabolism via CYP2C9 Monitor more closely monitor FBC regularly. Avoid co-administration of cimetidine with cyclophosphamide... 

Chlorambucil A favourable influence on laboratory parameters and on inflammatory changes in histology was observed, but the morphological progression of PBC was not halted. Moreover, therapeutic use of chlorambucil is unacceptable owing to the danger of bone-marrow toxicity. (138)... 

Chlorambucil acts most slowly and is the lea.st toxic i any nitrogen mustard derivative in use. It is indicated es x cially in treatment of CLL and primary maeroglobuliiKiuu... 

Chlorambucil is noncombustible, but toxic, corrosive, or flammable thermal decomposition products such as carbon monoxide, hydrogen chloride, and oxides of nitrogen may form if involved in a fire. Because of possible aquatic toxicity concerns. 

Drugs with ovarian toxicity (busulfan, chlorambucil, cisplatin, cyclophosphamide, fluorouracil)... 

Chlorambucil, melphalan, and uracil mustard also have been associated with pulmonary fibrosis. Of the alkylating agents, only nitrogen mustard and thiotepa have not been reported to cause fibrotic pulmonary toxicity. ... 

Ever since MOPP therapy was created and the efficacy confirmed, researchers tried to modify the regimen in an attempt to improve efficacy and decrease toxicity. Some MOPP variations include MVPP (vinblastine substituted for vincristine), CVPP (cyclophosphamide substituted for mechlorethamine), and ChlVPP (chlorambucil substituted for mechlorethamine, and vinblastine substituted for vincristine) were attractive alternatives to MOPP because they offered equal efficacy and differing or less severe toxicities. The various combination chemotherapy regimens appear to produce initial complete response rates in over 80% of the patients treated, and result in a 55% to 65% cure rate for advanced Hodgkin s lymphoma. 

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. 

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