ALKYLATING AGENTS &

PLATINUM ANALOGS
• Alkylating agents are drugs that alkylate (donate an alkyl group to) other
molecules by covalent bonds.
• They also alkylate DNA, RNA and various enzymes and there is interstand
cross-linking of DNA.
Actions :
Alkylating agents exert
1. Cytotoxic effects: Alkylating agents destroy the rapidly multiplying
cells—both cancer cells and normal host cells.
2. Immunosuppressant effects: Alkylating agents are good
immunosuppressants for which they are used in rheumatoid arthritis and
other autoimmune disorders.
3. Radiomimetic effects: The actions of alkylating agents resemble that of
radiotherapy
Cyclophosphamide:
• Cyclophosphamide is a prodrug converted to the active metabolite
aldophosphamide in the liver.
• Aldophosphamide is inturn converted to phosphoramide mustard and
acrolein.
• Phosphoramide is thought to be responsible for cytotoxic activity while
acrolein causes adverse effects.
• Cyclophosphamide is well absorbed on oral administration with high
bioavailability and, therefore, it can be given orally or iv. It also has
immunosuppressant properties.
Adverse effects:
• Apart from common adverse effects to anticancer drugs,
cyclophosphamide causes cystitis due to a metabolite acrolein.
• This can be prevented by giving IV Mesna, irrigating the bladder with
acetylcysteine, and by giving large amounts of fluids.
Uses
• Cyclophosphamide can be used in Hodgkin’s lymphoma in place of
mechlorethamine in MOPP regimen.
• In non-Hodgkin’s lymphomas (NHL), it can be used with doxorubicin (hydroxy–
daunomycin), vincristine (oncovin) and prednisolone (CHOP regimen).
Cyclophosphamide is also useful in Burkitt’s lymphoma in children, leukemias
and myeloma.
• Cyclophosphamide is an immunosuppressive agent.
Dose: 2–3 mg/ kg/day oral. CYCLOXAN, ENDOXAN 50 mg tab 200, 500, 1000
mg inj.
BUSULPHAN
• Busulfan, an alkyl sulfonate, has selective activity against cells of the myeloid
series and was the drug of choice in chronic myeloid leukaemia—but now other
drugs are preferred .
• Busulfan can cause skin pigmentation, hyperuricaemia, gynaecomastia and
pulmonary fibrosis
Platinum Analogs
• Cisplatin, carboplatin and oxaliplatin are platinum containing compounds.
They get converted to the active form in the cell, inhibit DNA synthesis
and cause cytotoxicity almost like alkylating agents.
• Cisplatin causes ototoxicity with tinnitus, loss of hearing and
nephrotoxicity. To reduce nephrotoxic effects, cisplatin is given as slow
infusion with adequate hydration and a diuretic.
• Cisplatin is particularly emitogenic but vomiting is often well controlled
with a 5-HT3 antagonist like ondansetron.
• Though peripheral neuropathy and anaemia can occur, cisplatin is
relatively less toxic to bone marrow.
• Cisplatin is used in solid tumours like ovarian, testicular and bladder
cancer and cancers of the head and neck;
• Carboplatin is a less toxic derivative of cisplatin
Advantages over cisplatin are:
• Carboplatin is less nephrotoxic and does not require strict hydration
unlike cisplatin
• Less toxic to gut—less vomiting
• Milder neurotoxicity
• Milder ototoxicity
For the above reasons, it is better tolerated and is often preferred in place of
cisplatin. However, it is more bone marrow toxic.
bmchselaiyurchennai bharathsuperspecialityhospital