Review of Pharmacology - 9E (2015)

Review of Pharmacology
Marrow sparing cytotoxic drugs
• Vincristine
• Bleomycin
• L-asparaginase
whereas vincristine is ‘marrow sparing’ but is neurotoxic (peripheral neuropathy). Vinca
alkaloids can also result in SIADH.
• Vinblastine’s most important clinical use is the curative therapy of metastatic testicular
tumors.
• Vincristine with glucocorticoids is the treatment of choice for inducing remission
in childhood leukemias. It can also be used for pediatric solid tumors (Wilm’s tumor,
neuroblastoma and rhabdomyosarcoma) and lymphomas.
Chemotherapy C: Antineoplastic Drugs
640
Irinotecan is now the treatment
of choice for advanced colorectal
carcinoma in combination with
5-FU.
Etoposide induced secondary
leukemia
• Develops at short time interval
• Lacks preceeding myelodysplastic
stage.
Taxanes
Paclitaxel and docetaxel interfere with mitotic spindle formation by preventing disassembly
of microtubules. Paclitaxel causes hypersensitivity reactions (due to Cremophor-containing
vehicle) whereas docetaxel is devoid of this adverse effect. Protein bound paclitaxel (nabpaclitaxel)
has decreased risk of hypersensitivity reactions. Both of these drugs can cause bone
marrow suppression and neurotoxicity. Cisplatin decreases paclitaxel clearance and paclitaxel
can decrease doxorubicin clearance. Cabazitaxel is a microtubule inhibitor indicated in
combination with prednisone for hormone refractory metastatic prostate cancer.
Ixabepilone
It is a new drug approved for treatment of advanced breast carcinoma resistant to anthracyclines
and taxanes. It is given in combination with capecitabine. It acts by binding to tubulin and
promoting microtubule stabilization, thereby arresting cells in the G 2
-M phase of cell cycle.
Erbulin Mesylate
It is a microtubule inhibitor recently approved for treatment of patients with metastatic
breast cancer.
Estramustine
It is a combination of estrogen and mechlorethamine (nitrogen mustard) and is used for
the treatment of prostatic carcinoma. It acts as anti-mitotic drug by binding to tubulin. It can
produce estrogenic side effects (gynaecomastia and impotence).
Topoisomerase Inhibitors
Camptothecins
Irinotecan and topotecan are obtained from Camptotheca acuminata tree and act by inhibiting
topoisomerase I (this enzyme nicks, introduces negative supercoils and reseals the DNA
strand). Topotecan is used in advanced ovarian carcinoma and is excreted by renal route.
Irinotecan is a prodrug that is converted in the liver to an active metabolite, SN-38. It is
eliminated in bile and feces and thus its dose should be reduced in hepatic failure. Irinotecan
is now the treatment of choice for advanced colorectal carcinoma in combination with 5-FU.
• Dose limiting toxicity of topotecan is neutropenia whereas it is diarrhea for irinotecan.
• Irinotecan can also lead to myelosuppression.
• Irinotecan can also result in a cholinergic syndrome (manifested as diarrhea, sweating,
hypersalivation, lacrimation, rhinorrhea, abdominal cramps and bradycardia) due
to inhibition of acetylcholine esterase. It occurs within 24 hours.
Epipodophyllotoxins
Podophyllotoxin was used for its emetic, cathartic and antihelminthic effects. It acts by binding
to tubulin but its derivatives; etoposide and teniposide act by inhibiting topoisomerase
II resulting in DNA damage through strand breakage. These drugs act at the junction of
late S and early G 2
phase of cell cycle. These drugs can cause gastrointestinal distress and
myelosuppression.
• Etoposide is indicated for testicular, prostatic and oat cell carcinoma [of lung].
• Etoposide therapy can result in acute non-lymphocytic (acute monocytic or monomyelocytic)
leukemia. This leukemia develops at a short time interval (1 to 3 years)
after the end of therapy as compared to alkylating agents induced leukemia (require
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