This document discusses chemotherapy in gynecology. It describes the clinical uses of chemotherapy including as a sole treatment, as an adjuvant therapy after surgery, or as a neo-adjuvant therapy along with surgery or radiotherapy. It discusses concepts such as complete response, partial response, and cell cycle phases. It also covers factors important to chemotherapy like drug administration methods, essential investigations, precautions, complications, mechanisms of action for various drugs, and treatment of some specific gynecological cancers.

1. Chemotherapy in Gynaecology
The use of drugs to treat diseminated cancer
Clinical use of chemotherapy
1. The sole method of treatment
2. An adjuvant therapy—after surgery for occult
disease.
3. A neo- adjuvant –along with surgery or
Radiotherapy.
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2. Complete response
Disappearance of measurable disease in
Four weeks.
Partial response
Reduction of more than 50% of tumour mass
In 4 weeks.
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3. Chemotherapy and cell cycle
Cell cycle time
The time needed by a proliferating cell to
progress through the cell cycle and produce a
daughter cell.
Doubling time
Time taken for tumour cell population to double
in rapidly growing solid tumour, slowing of
doubling time.
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4. Cell loss - determines the tumour growth rate.
Death of cells, migration or metastasis.
Growth fraction - the number of dividing cell In a
tumour.
100% in rapidly growing tumour.
Actively growing cells are most vulnerable to
chemotherapy
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5. Cell Cycle
Four phases
1. G1 – protein synthesis phase
2. S phase – DNA is copied and
synthesised prior to cell division
3.G2 & M phase – chromosome
condensation
and segregation.
4. G0 – resting phase -programmed cell
Death (apoptosis)
A few cells to cell cycle.
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6. Lethal effect of CT agent : According to cell cycle
Phase
Cisplatin,Carboplatin
Alkylating agent -- all phases, but more in
G2 & G1/S boundary.
Antimetabolites -- in S phase
Etoposide.Taxanes -- in G2'M phase.
Vinka alkaloids
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7. Other factors of importance in CT
1. Length of therapy
2. Tissue concentration of the drug.
3. tumour load at the start of therapy.
Tumour with large growth fraction
- high dose intermittent therapy.
Slowly growing tumour( small growth fraction )
- continuous Tt.
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8. Combination of antitumour drugs
Concurrent / sequential – to increase
The effectiveness.
Less toxicity and less chance of
resistance.
Superior to single agent in leukaemia,
Lymphoma & some ovarian tumours.
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9. Cell kill hypothesis
Which states that , the effect of cancer therapy on
tumour cell population demonstrate first order
kinetics; i.e, the proportion of tumour cells killed is
a constant percentage of the total number of cells
present. It is proportional to the dose of the drug
used. 9
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10. Clinical considerations during CT
1. Administration of drug
Single drug therapy
Sequential drug therapy
Combination drug therapy.
Advantages of combination therapy
Greater therapeutic response
Less toxicity
Drug resistance is less or delayed
Higher rate of complete remission
Long period of disease free interval 10
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11. Disadvantages of combination therapy
Hospitalisation is needed
Careful and well supervised monitoring
Cost of Tt is high
Work- up and supervision of the patient
Pathological diagnosis and extent of the
Disease must precede initiation of Tt
Evaluation of general condition of the Pt
Periodic review of response to Tt
Evaluation of vital organs
Tumour markers before and after Tt 11
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12. 3. Essential investigations during Tt
Haemoglobin and platelet count
Renal function tests
( renal toxic drug like methotrexate )
Liver function tests
ECG and cardiac function
( cardiotoxic drugs -adriamycin)
PFT ( pulmonary toxic drug- Bleomycin)
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13. Special precautions during Chemotherapy
Antiemetic before the drug therapy
(Metoclopramide, Chlorpromazines)
Renal toxic drug- hydration before & after Tt
For I/v access, use angiocath
Inspect for evidence of fungal infection
Granulocytes < 1000/ c mm, stop drug.
- give blood transfusion
Platelets < 40000/ cmm, stop drug. Give
Blood transfusion and platelet 13
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14. Complications of chemotherapy
CT drugs acts on malignant and normal cells
Toxicity
1. Bone marrow suppression
( low WBC and platelet count (Nadir value)
1O days after alkylating agents,15-16 days
After carboplatin)
Not for Vinka alkaloids & bleomycin.
2. Nausea and vomiting
Most emetogenic – cisplatin, doxorubicin
Less emetogenic - carboplatin
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15. 3. Alopecia
Temporary – cyclophosphamide, taxanes,
Doxorubicin & etoposide
No hair loss – carboplatin & cisplatin
Scalp cooling reduce hair loss.
Cannot tolerate for > 1 hour.
4. Renal toxicity
Methotrexate and cisplatin
Pre and post chemotherapy hydration
Carboplatin – no renal toxicity
Cisplatin – Hypomagnesaemia- self limiting 15
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16. 5. Cardiotoxicity
Doxorubicin- cardiomyopathy , conduction
Problem and CCF .
6. Lungs – Bleomycin – pulmonary fibrosis.
X- ray chest & PFT before Tt.
Inform anaesthetist beforehand
7. Liver – Methotrexate – hepatocellular damage
Doxorubicin – excreted in bile
Cyclophosphamide- activated in liver
8.Reproductive system
Infertility
( successful pregnancy after Tt for
Germ cell tumour of ovary ) 16
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17. Fertility not returned after cyclophosphamide
And procarbacin ( Hodgekins disease)
Menstruation -Permanent cessation in
elderly.
Temperorly in young.
In pregnancy – abortion & congenital defects
9. Skin – skin rashes and pigmentation
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18. mechanism of action
A. drugs interfering with the biosynthesis of DNA,
RNA and tissue proteins
1. Antimetabolites
Folic acid analogue – methotrexate
Purine analogue – 6- mercaptopurine
Pyrimidine analogue – 5- FU
2. other agents with similar action
Hydroxyurea
Procarbazine
B. Drugs interfering with replication, transcription
And translation
1. Interfering with replication
a. Alkylating agents
Nitrogen mustard, chlorambucil
Cyclophosphamide, Melphalan.
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19. b. Ethylene amines
Triethylene melamine ( TEM )
Hexamethyl melamine, Tri ethylene
Thiophosphoramide ( thio-TEPA )
c. Sulfonic esters
Piperazine derivatives, Mitomycin-C
2. drugs interfering with transcription
a. Actinomycin
b. Mithramycin
c. Quinacrine
d. Daunorubicin
3. drugs interfering with translation
a. puromycin 19
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20. C. Agents with radio- mimetic effects
a. Bleomycin
b. Streptonigrin
D. Agents intering with mitotic spindle
a. Colchicine
b. Vincristine
c. Vinblastine
E. Inhibitors of protein synthesis
a. L- Asparginase
b. Azaserine
D. Oter drugs
a. DTIC
b. Triolone
c. Chalones 20
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21. G. New drugs
a. Cisplatin
b. Carboplatin
c. Etoposide,
d. Taxanes
Paclitaxel ( Taxol ) singly or combination
Duration of therapy
Not definite
A tumour- not palpable contains many
cells – need further therapy.
6 - 12 months or five courses of Tt.
Tumour marker
Dose – depends on Ht, Wt and surface area.
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22. Routes of administration
a. i/v, i/m
b. Oral,
c. Intra peritonial
d. intrapleural
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23. TREATMENT OF SOME GYNAEC CONDITIONS
CA vulva
5 FU ( 5 – fluorouracil)
Local excision
Ca Vagina
Meta stasis of chorio Ca – Methotrexate
and Actinomycin D
Ca Cervix
Doxorubicin 120mg/mtsq + Cisplatin 50 mg/kg IV over
24 hrs weekly for 6 cycles
Endometrial Ca
CT less used
Surgery with radiotherapy – main Tt
Metastasis – Progesterone (MDPA 1gm I/M weekly or 400mg/day
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24. CA Ovary
Major role after surgery
Prophylactic post op. CT in stage 1C
In advance stage – palliative therapy
Unresectable tumor, CT followed by debulking
Cisplatin & Taxol – main drugs
Carboplatin – less emetic
less nephrotoxic
less mylosuppression
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25. Immunotherapy
To improve the immunity of the patient
Gene therapy – under research
Stem cell therapy
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26. Thanks
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