Chemotherapy In Cancer

Definition
Chemotherapy is the therapeutic use of chemical agents to treat a disease especially
through administration of one or more cytotoxic drugs to destroy or inhibit the growth &
division of cancer cells.

Mechanism of Action
Cancer is uncontrollable growth of cells coupled with malignant behaviour (invasion &
metastasis) caused by interaction between genetic susceptibility & environmental factors.

These factors lead to accumulation of genetic mutations as oncogenes (genes that control
growth rate of cells) & tumour suppressor genes (genes that help to prevent cancer) which
gives cancer cells malignant characteristics.

Most chemotherapeutic agents works by impairing mitosis effectively by targeting fast

dividing cells.They prevent mitosis by various mechanisms including:
- Damaging DNA
- Inhibition of the cellular machinery involved in cell division
- Induction of a programmed form of cell death called apoptosis

As chemotherapy affects dividing cells,so tumours with high growth rates as acute
myelogenous leukaemia & aggressive lymphoma including Hodgkin's lymphoma are more
sensitive to chemotherapy. Unfortunately, tumours with slower growth rates such as
indolent lymphoma are less sensitive to chemotherapy. Heterogenic tumours may display
varying sensitivity to chemotherapeutic agents.

Other Uses
Chemotherapy is a broad term including cytotoxic agents and antimicrobial agents
Some chemotherapeutic agents used in diseases other than cancer such as autoimmune
disorders & non-cancerous plasma cell dyscriasis
They are often used in lower doses which means minimal side effects such as:

- Methotrexate in rheumatoid arthritis, psoriasis & ankylosing spondylitis

- Cyclophosphamide in lupus nephritis in SLE

Cyclophosphamide also can be used before bone marrow transplantation (hematopoietic

stem cell transplant)

Efficacy
Efficacy of chemotherapeutic agents depends on,
- Cancer type
- Stage of the Cancer
- Type of chemotherapy used
- Dosage of the chemotherapeutic agents
Types
Anticancerous drugs are classified into
1) Anti metabolites
- Folic acid antagonist: Methotrexate
- Purine antagonist: Mercaptopurine, Azathioprine
- Pyrimidine antagonist: 5-Flurouracil

2) Alkylating agents
- Nitrogen Mustards: Cyclophosphamide
- Nitrosources: Carmustine, Lomustine
- Alkyl sulphonates: Busulphan

3) Plant alkaloids
- Vinblastine
- Vincristine

4) Cytotoxic antibiotics
- Actinomycin D
- Bleomycin
- Doxorubicin

5) Hormones & Anti-hormones

- Oestrogen: Prostate cancer
- Progesterone: Endometrial cancer
- Androgen: Breast cancer
- Cortisone: Acute lymphocytic leukaemia (ALL)
- Anti-oestrogen: Tamoxifen in Breast cancer
- Anti-androgen: Flutamide in Prostate cancer
- GnRH Analogue: Leuprolide in Prostate cancer

6) Radioactive isotopes
- Iodine 131: Cancer Thyroid gland
- Phosphorus 32: Polycythemia Vera

7) Miscellaneous agents
- Asparaginase enzyme
- Cisplatin
- Procarpazine
- Hydroxyurea
- Interferons

Treatment strategies
Chemotherapy:
May be given to cure or to palliate the patient
May be given as neo-adjuvant or as adjuvant therapy
May be given alone or with other cancer treatment options
May be one type only or combination therapy
Common combinations in chemotherapy regimens

Cancer Type Drugs Acronym

Breast Cancer Cyclophosphamide, CMF
Methotrexate, 5-flurouracil
Doxorubicin, AC
Cyclophosphamide
Hodgkin’s Lymphoma Docetaxel, Doxorubicin, TAC
Cyclophosphamide
Doxorubicin, Bleomycin, ABVD
Vinblastin, Dacarbazine
Mustine, Vincristine, MOPP
Procarbazine, Prednisolone
Non Hodgkin’s Lymphoma Cyclophosphamide, CHOP
Doxorubicin, Vincristine,
Prednisolone
Germ Cell Tumour Bleomycin, Etoposide, BEP
Cisplatin
Stomach Cancer Epirubicin, Cisplatin, 5- ECF
Flurouracil
Epirubicin, Cisplatin, ECX
Capecitabine
Colorectal Cancer 5-Flurouracil, Folinic acid, FOLFOX
Oxaliplatin
Bladder Cancer Methotrexate, Vincristine, MVAC
Doxorubicin, Cisplatin
Lung Cancer Cyclophosphamide, CAV
Doxorubicin, Vincristin

Route Of Administration
- Intrravenous (the most common)
- Orally
- Intramuscular
- Subcutaneous
- Intrathecal (into the fluid around spinal cord)

Whatever the route of administration, it eventually reached the bloodstream and carried
throughout the body so that they can reach to the cancer cell.

Side Effects
Side effects comes from the fact that the drug cannot differenciate between cancer cells &
other rapidly dividing cells in the body such as:
- hair follicles
- bone marrow
- lining of the mouth
Not everyone receives chemotherapy will experience side effects but it should be
remembered that most side effects aretemporary & gradually disappeared once your
treatment has stopped

Side effect varies according to the regime choosed but m/c side effects are:

1)Bone marrow suppression = Myelosuppression

- WBCs: Leukopenia = Infections
- RBCs: Anemia
- Platelets: Thrombocytopenia = Bleeding

2) Hair loss

3) Skin changes

4) GIT problems
- Anorexia, nausea, vomiting, diarrhoea
- Stomatitis & mouth ulcers
- Taste changes

5) Hepato & oto toxicity

6) Urate nephropathy

7) Gonadal Cells
- Sterility
- Teratogenicity
- Mutagenicity

8) Delayed wound healing

9) Carcinogenicity

Limitations
Chemotherapy does not always work and even when it is useful it may not completely
destroy the cancer. Blood brain barrier psoas an obstacle to delivery of drugs to brain.
Blood vessels of the tumours are very different from those seen in normal tissues. Tumour
vasculature is poorly formed and does not deliver an adequate blood supply to all areas of
the tumour. This leads to issues with drug delivery because many drugs will be delivered
to the tumour by circulatory system.

Resistance
Resistance is a major cause of failure in chemotherapy. Few possible causes of resistance
in cancer.

One of them is the presence of small pumps on the surface of cancer cells that actively
move the chemotherapy drugs from inside to outside the cell. Cancer cells produce high
amounts of these pumps which called p. glycoproteins.
Another mechanism of resistance is gene amplification; a process in which multiple cop ies
of genes are produced by cancer cells. They overcome the effect of drugs that reduce the
expression of genes involved in replication, with more copies of the genes, drugs cannot
prevent all expressions of the genes. Therefore the cell can restore its proliferative ability.