Chemotherapeutic Agents Action Cell Cycle,Side Effects

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CHEMOTHERAPY- GENERAL GUIDELINES

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Chemotherapeutic Drugs Types and Agents

Chemotherapeutic Agents Faq's

Dr Ira Shah
M.D, DCH (Gold Medalist), FCPS, DNB
Edited by Dr. Bharat R Agarwal
Consultant Pediatric Hematologist and Oncologist.

Q. Is it true that different chemotherapeutic agents act at different cell cycles?

A. Yes that is true. The cell cycle is divided into the following stages:

G0 phase-resting cells
G1 phase-proteins and RNA are synthesized
S phase-cellular contents of DNA doubles
G2 phase-DNA synthesis ceases. Microtubules are formed for mitosis.
M phase- Mitosis

+ Cells in the G0 phase are usually refractory to chemotherapy.
+ G1 phase specific drug is L-asparaginase
+ S phase specific drugs are procarbazine, cytarabine, Hydroxyurea, 6-Mercaptopurine, Methotrexate,6-Thioguanine etc.
+ G2 phase specific drugs are Bleomycin, Etoposide.
+ M phase specific drugs are Vincristine and Vinblastine.

Tumors with a large proportion of cells in G0 tend to be relatively chemoresistant. An initial reduction in tumor cell population (e.g. by surgery or radiotherapy) may bring resting cells into cycle (recruitment) thus increasing the susceptibility of cells to subsequent chemotherapy.

Q. How are these agents given?

A. Some drugs like Vincristine, Doxorubicin should be given only intravenously and some drugs like Mercaptopurine, Prednisone are given orally. Preservative-free Methotrexate can be given intrathecally to destroy the cancer cells in the CNS in diseases like Acute leukemias and lymphomas.

All pediatric oncology centers have treatment protocols for cancers. Some commonly used protocols are as follows:

Hodgkin's lymphoma-

COPP Protocol - Cyclophosphamide, Oncovin(Vincristine), Prednisolone and Procarbazine.
ABVD Protocol- Adriamycin, Bleomycin, Vinblastine and Dacarbazine.

Non-Hodgkin's lymphoma-

COMP Protocol - Cyclophosphamide, Oncovin, Methotrexate and Prednisolone.
CHOP Protocol - Cyclophosphamide, Hydroxydaunorubicin (Doxorubicin), Oncovin and Prednisolone.

Most of the anticancer drugs are metabolized in the liver and excreted by the kidneys. Hence, before starting chemotherapy, a base line investigation to rule out existing liver and kidney dysfunction should be done.

Q. What are the side effects of these agents?

A. Since they act on rapidly dividing cells, their major toxic effects are seen on the bone marrow, GI tract, and skin and hair. Most of these agents cause nausea, vomiting, mucositis, bone marrow suppression, alopecia and diarrhea. Other side effects are more specific to particular agents e.g.

Prednisolone - Bilateral necrosis of head of femur, cushingoid appearance
Cyclophosphamide - Sterility, Hemorrhagic cystitis
Ifosfamide - Hemorrhagic cystitis
Daunorubicin - Cardiomyopathy
Doxorubicin - Cardiomyopathy
Bleomycin - Pulmonary fibrosis
L- asparaginase - Pancreatitis, Thromboembolic phenomenon
Vincristine - Peripheral neuropathy

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