Overview of Gynaecological Cancer Treatment

Cancers that occur in the reproductive tract organs of females are called gynecological cancers.

Named according to the part of the tract where the cancer occurs.

Ovarian- many types of cancers occur in the ovary, most common is epithelial.

Tubal cancer- very rare, most are secondary

Uterine-cancers- most common is endometrial carcinoma.

Cervical cancer is the commonest gynecological cancer in the developing countries

Vaginal cancers

Vulval cancers

Choriocarcinomas and placental site tumors- these are pregnancy related cancers

• Dependent on site of cancer
• Abnormal vaginal bleeding especially postmenopausal
• Offensive vaginal discharge
• Abdominal mass
• Ulcers/sores on the vulva
• Wart like growths

Increasing age

Exposure to hormones-either produced in the body or taken as medication

Viral infections-human papilloma virus

Strong family history

Diagnosis is usually by biopsy of the tissue and histology of the sample

Sometimes in cases of pregnancy related cancers estimation of level of HCG may be used

Treatment is usually multi-disciplinary (different professionals working as a team.

Dependent on

• Type
• Stage
• General health of the woman

SURGERY –is the main stay of treatment for gynecological cancers especially when early diagnosis is made.

Chemotherapy - cytotoxics and hormones

Radiotherapy

Palliative

4 phases

1. G1—synthesis of enzymes and regulatory protein prior to DNA synthesis (resting)
2. S phase—DNA synthesis and replication
3. G2 phase—RNA, protein synthesis
4. M phase –Mitosis

Cell cycle time—denotes time taken by proliferating cell to go through the cell cycle and produce a new daughter cell

Varies but is fairly constant for a specific tumor

Cell cycle concept is very important for cancer chemotherapy

Dividing cells are most sensitive to cytotoxic agents

Synergistic combinations of drugs with better cancer killing potentials.

Chemotherapeutic agents are of 2 varieties

• Cell cycle non-specific
• Cell cycle specific

Cell cycle non-specific

• Cisplatin
• Carboplatin
• Cyclophosphamide

Cell cycle specific

• G1—Actinomycin D
• S phase— Methothrexate, 5FU etc.
• G2 phase— Etoposide, Bleomycin
• M phase— Vinblastine, vincristin
• Go phase- Nitrosureas

Principles

Rapidly growing tumors are more amenable

Constant fraction of neoplastic cells are killed with each dose

Effect of drugs depend on

• Mass and growth rate
• Sensitivity of resting phase cell
• Immuno-competence of host cell
• Type and schedule of agents

Combination chemotherapy is superior.

Drugs used should have different mechanism of action, different range of toxicity, synergistic effect

Dose is adjusted according to the tolerance of patient and pretreatment evaluation must be done

Precautions

Do not mix the drugs

Flush infusion set with normal saline in between the drugs.

To avoid sclerosis of vein, run some normal saline after each drug/avoid extravasation

Give antiemetics before start of therapy

Based mainly on mechanism of action and structural similarity.

Alkylating agents

Transfer their alkyl radicals to nucleic acids, prevent cell division by cross-linking the DNA strands, are CCNS and are good for bulky slow growing tumors (e.g. cyclophosphamide, the platinum agents)

Antimetabolites

Act by inhibiting essential metabolic agents required for synthesis of purines, pyrimidines and nucleic acid

Examples:

• Methotrexate, a folic acid antagonist, prevents reduction of folic acid to folinic acid by inhibiting dihydrofolate reductase.
• 5-Fluorouracil, a pyrimidine analogue, blocks thymidine synthesis and prevents DNA replication
• 6- Mercapto-purine, a purine derivative, attaches to enzyme catalytic site

Antibiotics

Prevent DNA replication, cause single and double stranded DNA breaks. CCNS

e.g.

• Actinomycin D
• Bleomycin
• Doxorubicin, etc.

Plant derivatives and Taxane

Cell cycle specific. They act as spindle poison and arrest mitosis at metaphase.

E.g. Vincristine and vinblastin (from plant vinca rosea).

Taxanes, obtained from bark of pacific yew tree(taxus brevifolia) act to disturb assembly and stabilization of microtubules e.g. Paclitaxel and docetaxel

The camptothecin analogs, Topotecan and Irinotecan inhibit topoisomerase-I causingle stranded DNA break.

Other plant derivative include etoposide

Hormones

These drugs induce regression of hormone responsive tumor.

Progesterone preparations e.g. hydroxyprogestrone caproate, medroxyprogestrone acetate etc..

Antiestrogens e.g. Tamoxifen acts by competitive receptor binding, helpful in estrogen dependent tumors

Miscellaneous

Hexamethylamine: acts as antimetabolite

Hydroxyurea: increases radiosensitivity of malignant tissues.

Biological: interferon, antibodies etc. act by increasing host immune defense