CHEMOTHERAPY PART 2

Dr. Alfeches Lecture

Purine Antagonist
6-Thiopurines
6-MP, 6-Thioguanine
o Converted to nucleotides by
enzyme hypoxanthine-guanine
phosphoribosyl transferase
o Given orally
o Equivalent myelosuppression
occurs in both 6-MP and 6-TG
o Metabolism of 6-MP is inhibited
by allopurinol
6-MP converted to an
inactive metabolite by an
oxidation reaction catalyzed
by xanthine oxidase
Allopurinol + 6-MP= excess
toxicity
Does of 6-MP
reduced by 5075%
o Myelotoxic with peak neutropenia
and thrombocytopenia in 7 days
Fludarabine
Purine analog active in CLL and low grade
lymphoma
Rapidly dephosphorylated to 2-fluoroarabinofuranosyladenosine
Phosphorylated intracellularly by
deoxycytidine kinase Tripohosphate
Inhibition of DNA synthesis and function
Intravenously
Renal excretion
Main dose limiting toxicity:
myelosuppression
Patients using fludarabine should receive
PCP prophylaxis using cotrimoxazole
Cladribine
Purine nucleoside analog with high
specificity for lymphoid cells
Active in hairy cell leukemia, CLL, low
grade lymphomas
Intravenous
Renal excretion

Major toxicities: myelosuppression, fever,

opportunistic infection

Vinca Alkaloids
- Binds to microtubules and inhibit mitotic
spindle formation
- Resistance occurs by acquisition of
multidrug resistance phenotype or
development of microtubules with
decreased vinca alkaloid binding
1.
2.
-

Vincristine
Administered intravenously
Metabolized in the liver= 70%
BHL, HL, ALL, MM, Ewings sarcoma,
Wilms tumor, rhabdomyosarcoma
Dose limiting toxicity: neurotoxicity
(paresthesia of the fingers and lower legs,
loss of deep-tendon reflexes
Constipation is common
Cranial nerve palsies, ataxia, seizure,
coma
Bone marrow suppression is not common
Vinblastine
Alkaloid derived from Vinca rosea
Metablized by the liver P450 system
Majority of the drug excreted in the feces
via the hepatobiliary system
Potent vesicant
Adverse effect: nausea, vomiting, bone
marrow suppression, alopecia
HL, NHL, Breast cancer

Antitumor Antibiotics
1. Anthracyclines
2. Doxorubicin
3. Daunorubicin
4. Idarubicin
5. Epirubicin
6. Mitoxantrone
Main dose-limiting toxicity of all
anthracyclines: