Chemotherapeutic DrugsThe various anti-
cancer drugs are classified as:
Other agents with alkylator activity are:
- Carmustine, etc.
- Cytosine (Cytarabine, Ara-C)
- 5- Fluoro uracil
- Actinomycin D
MECHANISM OF ACTIONMost chemotherapeutic agents exert their major toxic and anti-tumor effect by inhibiting the DNA synthesis of malignant and dividing cells. Hence, bone marrow and intestinal mucosa suffer the most toxicity.
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.
ROUTE OF ADMINISTRATIONSome 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:
COPP Protocol - Cyclophosphamide, Oncovin(Vincristine), Prednisolone and Procarbazine.
ABVD Protocol- Adriamycin, Bleomycin, Vinblastine and Dacarbazine.
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.
ADVERSE EFFECTSSince 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
MONITORING ON CHEMOTHERAPYMost of the drugs depress the bone marrow. The bone marrow function can be assessed by doing the blood cell counts (RBC counts, Hemoglobin, Platelet count, white cell count etc). The blood counts may fall at any time during the treatment or soon after that (usually about a week following intensive regimes). Blood counts should be checked ideally every day during intensive treatments and once in a week during maintenance treatments. Usually, the drugs are given only if the absolute neutrophil count is above 1000/cu mm (some centers take 1500/cu mm as the lower limit) and platelet count above 100,000/cu mm. However, during induction phase in Acute leukemia, treatment should continue as far as possible to prevent the inhibitory effect of the blast cell on the normal cell population in the bone marrow.
Vomiting on chemotherapy
Most chemotherapeutic agents produce vomiting for about 24 hours or a little longer. The various anti-emetics used are:
Antiemetic therapy should begin before the chemotherapy starts and not after the patient has started vomiting.
Ideally for intravenous injection, a venflon or a butterfly needle should be used. Metacarpal veins on the dorsum of the hand are usually preferred. Bruised and inflamed areas should be avoided. Each vein should be tested with normal saline before injecting chemotherapy and should be well flushed after administration.
If there is any leakage of vesicant drugs into the tissue, these will be severe necrosis and ulceration. Extravasation should be suspected if :
- Swelling arises at the site of the needle.
- The patient complains of a sharp stinging or burning sensation around the needle or cannula site.
- No blood is obtained with pull on the syringe.
- Resistance is felt on the plunger of syringe during bolus administration.
- Free flow of fluid is absent if an infusion is in progress.
If these signs are present, then stop administration immediately. Withdraw any solution by pulling back on syringe. Remove the needle. Cover site with icepack. Inject hydrocortisone or dexamethasone around the entire area twice daily until all redness disappears. If very severe, then fasciotomy may be required.