principles of chemotherapy

Principles of cancer therapy

Cellular biology
There are two distinct phases in the life cycle of all cells :mitosis (M phase)and interphase, the interval between successive mitoses.
Interphase is subdivided into three phases:G1 phase , S phase ,and G2 phase
Some cells leave the cycle temporarly or permanently and enter the G0 or resting phase.

The growth fraction of the tumor is the proportion of actively dividing cells.

Chemotherapeutic agents and radiation kill cells by fist –order kinetics, which means that a constant proportion of cells is killed for a given dosage regardless of the number of cells prsent

Chemotherapyclassification of chemotherapeutic agents

1- cell cycle –nonspecific agents:such as alkylating agents, cisplatin , and paclitaxel
2-cell cycle-specific agents:like hydroxyurea and methotrexate act during S phase , bleomycin acts in G2 and vinca alkaloids act in M phase

Principles of chemotherapy

1-They are selected on the basis of previous experience
2-The drugs are usually given systemically so the tumor can be treated regardless of its anatomic location
3-To increase the local concentration, certain drugs may occasionally be administered topically by intraarterial infusion or by intrathecal or intracavitary 1


4-Chemotherapy is generally not administered if the white cell count is less than 3000/mm3 or if the platelet count is less than 100,000/ mm3
5-Nadir blood counts are obtained 7 to 14 days after treatment, and subsequent doses may need to be reduced,

6-Dosage reduction may also be necessary because of toxicity to other organs , such as GIT ,liver or kidneys
7-Resistance to chemotherapy may be temporary or permanent.
8-Temporary resistance is mainly related to the poorvascularity of bulky tumors and an increasing proportion of cells in the relatively resistant G0 phase

9-Permanent resistance mainly results from spontaneous muttation to phenotypic resistance and ocurrs most commonly in bulky tumors
10-Permanent resistance may also be acquired by frequent exposure to chemotherapeutic agents

Chemotherapeutic agents

The common agents used in gynecological malignancies:
Alkylating agents:cyclophosphamide
antimetabolites:methotrexate
Antibiotics:bleomycin ,doxorubicin
Plant alkaloids: vincristine
Other drugs:cisplatin

Radiation therapy

Radiation may be defined as the propagation of energy through space or matter.
Types of radiation :electromagnetic and particulate.


Electromagnetic radiation
Visible light
Infrared light
Ultraviolet light
X-rays (photons)
Gamma rays(photons)

Particulate radiation

Particulate radiation consists of moving particles of matter ,their energy consists of the kinetic energy of moving particles
The particles include the following:
Neutrons
Protons
electrons

Unit of radiation measurement

The Gray is equivalent to an absorbed energy of 1 joule per kilogram of absorbing material

Biologic considerations

Ionization of molecules:radiation damage is caused by the ionization of molecules in the cell , with the production of free radicals.
Oxygen effect:in the absence of oxygen ,cells show a twofold to threefold increase in their capacity to survive radiation exposure.


Pharmaacologic modification of the effect of radiation :a variety of chemical compounds are capable of enhancing the lethal effects of radiation.
Time- dose fraction of radiation:a dose that is too high sterilizes the tumor but results in an unacceptably high complication rate .if the interval between each fraction increases, the total dose must increase to produce the same biologic effect

Major factors influencing the outcome of radiation therapy

Normal tissue tolerance
Malignant cell type
Total volume irradiated
total dose delivered
Total duration of therapy
Number of fractions
Type of equipment used
Tissue oxygen concentration

Modalities of radiation therapy

In general , there are two radiation techniques:teletherapy and brachytherapy
In teletherapy , a device quite removed from the patient is used , as with external beam techniques.
In brachytherapy ,the radiation source is placed either within or close to the target tissue ,as with intracaitary and interstittial techniques.

External beam therapy

External radiation allows a uniform dose to be delivered to a given field
External radiation is usually used to shrink a large tumor mass before brachytherapy


Intracavitary radiation
It is used particularly in the treatment of cervical and vaginal cancer
All applicators now in use should be “afterloaded”which means that they are placed in the patient and their position checked by radiography before the radioactive substance is loaded into the applicator.

Interstitial radiation

In which the radioactive source is placed directly in the tumor may be delivered by removable or permanent implants
Permanent implants are used for inaccessible tumors.they use radioisotopes such as radon 222 or iodine 125 .
Removable implants are placed in tumors that are accessible (cervcal or vaginal tumors)

Complications associated with radiation

Acute complications:cellular swelling , tissue edema ,and tissue necrosis.acute cystitis, proctosigmoiditis, enteritis, bone marrow depression

Chronic complications:occur 6 months or more after radiation:

1- radiation enteropathy:proctosigmoiditis , ulceration, rectovaginal fistula, rectal or sigmoid stenosis, small bowel injuries.
2- vaginal vault necrosis
3- urological injuries:hemorrhagic cystitis and fistula

Hormonal therapy

The estrogen receptor (ER) status of primary and metastic breast cancer has been shown therapeutic and prognostic significance.
The (ER) and progesterone receptor (PR)status of endometrial cancer also have.


Clinical applications
Estrogen exposure increases the production of both ER and PR , whereas progestrone inhibits production of both ER and PR.
In breast cancer , patients whose tumors contain ER and PR have an 80% response rate to hormonal manipulation.
An objective response to progestin therapy occurs in about one third of patients with recurrent or metastatic endometrial carcinoma.

Pain mangement

Pain in gynecologic cancer may be the result of soft tissue infiltration , bone involvement , neural involvement, muscle spasm, infection within or near tumor masses , or bowel colic .
Peripherally acting drugs such as acetaminophen (paracetamol) should rarely be omitted from analgesic regimes, and rectal suppositories are useful if oral intake is not appropriate

Opioid use will be necessary for severe pain.

Controlled- release morphine tablets are a significant advance in convenience of administration as they need to be given only every 12 to 24 hours.
When pain is neurogenic in origin, an opioid and a peripherally acting drug should usually be supplemented by a tricyclic antidepressant , an anticonvulsant or a corticosteroid.

End of life issues

When it becomes clear that the patient is dying , the goal are to control symptoms .
Any unnecessary tube or equipment should be removed .
Nursing care should focus on pressure areas ,mouth care .with sublingual lorazepam if the patient is agitated

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