SEMINAR 2

CHEMOTHERAPY IN GYNAECOLOGY
BY:HASPREET
KHUGEN
SUKANYA
FARDEENA BEGUM
Introduction of chemotheraphy
-Inhibiting cell proliferation
-Cytotoxic drugs interfere with cell division at various points of the
cell cycle (i.e: S-phase {synthesis of DNA), M-phase {mitosis})
-Chemotherapy should be restricted to the patients in whom diagnosis of
cancer has been confirmed by either biopsy or cytology .
- All chemo-therapeutic agents have potential side effects, and it is
important to ascertain whether the patient has measurable disease and /
or elevated tumor markers
-Particularly before starting therapy in patients with metastatic disease ,
so that response can be assessed objectively.
ISSUES TO BE DISCUSSED
1. Natural History of the Particular Malignancy
a. Diagnosis of a malignancy made by biopsy
b. Rate of disease progression
c. Extent of disease spread

2. Patients Circumstances and Tolerance

a. Age, general health, underlying diseases
b. b. Extent of previous treatment
c. c. Adequate facilities to evaluate, monitor, and treat potential drug toxicities
d. d. The patients emotional, social, and financial situation

3. Likelihood of Achieving a Beneficial Response

e. Cancers in which chemotherapy is curative in some patients (e.g., ovarian germ cell tumors)
f. . Cancers in which chemotherapy has demonstrated improvement in survival (e.g., epithelial ovarian cancer)
g. Cancers that respond to treatment but in which improved survival has not been clearly demonstrated (e.g., metastatic
cervical cancer)
h. Cancers with marginal or no response to chemotherapy (e.g., melanoma)
• A course of chemotherapy involves one or more drug
• Each regimen is given at:
• Set time intervals
• Given number of cycles
• Eg: Carboplatin –Once every 3 weeks for a total of 6 cycles.
Methods used to assess:
• Clinical Examination
• Measurement of tumour markers
• Radiological imaging
CHEMOTHERAPEUTIC AGENT MECHANISM INDICATION RELEVANT SIDE EFFECTS
BIOLOGICAL AGENTS Bind to VGEF receptor Epithelial Ovarian HTN & GI perforation
Bevacizumab and prevent angiogenesis CA(EOCA)
PLATINUM DRUGS Inhibits DNA replication EOCA, CA Cervix & Nephrotoxicity,Neurotox
Cisplatin, Carboplatin Endometrium, Vulva icity.
TAXANES Inhibits mitosis during M EOCA, CA Cervix, Neurotoxicity
Paclitaxel phase by binds to tubulin Endometrium
Topoisomerase II inhibitors Inhibits the repair of EOCA, CA Myelosupression
double strand breaks in Endometrium,Uterine Mucositis
Doxyrubicin DNA sarcoma
ALKYLATING AGENTS Inhibits DNA replication CA Cervix Haemorrhagic Cysitits
Ifsofamide
ANTIMETABOLITES DNA synthesis inhibition Vulval Ca Mucositis
5 Fluorouracil
EOCA, Cervical CA Peripheral edema
Gemcitabine
ANTIOBIOTICS DNA synthesis inhibition Germ Cell CA Pulmonary fibrosis
Bleomycin
Side effects:
Cancer during pregnancy
• the diagnosis of cancer during pregnancy poses difficult dilemmas for
the pregnant patient, her family, and the medical team. Cancer in
pregnancy is rare, complicating up to 0.02% to 0.1% of pregnancies
annually.
• The cancers most commonly diagnosed in pregnancy are breast
cancer, cervical cancer, thyroid cancer, Hodgkin’s lymphoma, and non-
Hodgkin’s lymphoma.
Seminar 3
Chemotherapy in Gynaecology

Chemotherapy in Endometrial Cancer &

Cervical Cancer
By: Sukanya A/P Visvalingam (QIUP-201509-001893)
Quest International University

Endometrial Cancer
Chemotherapy is not used to treat stage I and II endometrial cancers.

Reserved to treat incurable patients with disseminated or recurrent endometrial

cancer, often after the failure of hormonal therapy

Chemo drugs used to treat endometrial cancer may include:

• Paclitaxel (Taxol)
• Carboplatin
• Doxorubicin (Adriamycin) or liposomal doxorubicin (Doxil)
• Cisplatin
• Docetaxel (Taxotere)
Quest International University

Most often, 2 or more drugs are combined for treatment.

The most common combinations include;

carboplatin/paclitaxel and cisplatin/doxorubicin.

Less often carboplatin/docetaxel and cisplatin/paclitaxel/doxorubicin may be used.

Quest International University

Sometimes chemo is given for a few cycles, followed by radiation. Then chemo is given
again. This is called sandwich therapy. It's sometimes used for endometrial papillary
serous cancer and uterine carcinosarcoma.

Another treatment option is to give chemo with radiationis also called chemoradiation.

The chemo can help the radiation work better, but it can be harder on the patient
because the combination causes more side effects.
Quest International University

Cervical Cancer
Chemo used to treat cervical cancer that has spread to other organs and tissues
(advanced cervical cancer). It can also be helpful when cervical cancer comes back after
treatment with chemoradiation (recurrent cervical cancer).

The chemo drugs most often used to treat cervical cancer that has come back or
spread to other areas include:
• Cisplatin
• Carboplatin
• Paclitaxel (Taxol)
• Topotecan
*Combinations of these drugs are often used.
Quest International University

For some stages of cervical cancer, the preferred treatment is radiation and chemo
given together is also called concurrent chemoradiation. The chemo helps the
radiation work better.

Options for concurrent chemoradiation include:

 Cisplatin given weekly during radiation. This drug is given into a vein (IV) before the
radiation appointment.
(If cisplatin is not a good option carboplatin may be used instead.)

 Cisplatin plus 5-fluorouracil (5-FU) given every 3 weeks during radiation.

Quest International University

Some other drugs can be used as well, such as;

 Docetaxel (Taxotere)
 Ifosfamide (Ifex)
 5-fluorouracil (5-FU)
 Irinotecan (Camptosar)
 Gemcitabine (Gemzar)
 Mitomycin
 Bevacizumab (Avastin)

Or any targeted drug can be added to chemo.

Vaginal Carcinoma and
Uterine sarcoma
By Khugen Raj
Vaginal carcinoma
• Can be divided into primary and secondary type
• The primary vaginal carcinoma should fulfil the following criteria.
• The primary site of growth is in the vagina.
• The cervix and the vulva must not be involved.
• There must not be clinical evidence of metastatic disease.
• Secondary vaginal malignancy follows carcinoma vulva, cervix or
urethra by direct spread.
Vaginal carcinoma
• Treatment
• Radiotherapy or surgery or the combination
is the accepted modality of therapy for
invasive primary carcinoma of the vagina.
• Stage 1 is treated with surgery
• Upper 1/3:Radical hysterectomy, partial
vaginectomy and bilateral pelvic
lymphadenectomy is the treatment of choice
• Lower-third:Radical vulvectomy with removal
of bilateral inguinofemoral lymph nodes along
with vaginectomy.
• Stage 2-4
• Radiation by external beam therapy with intracavity or interstitial radiation
• Chemotherapy is also an option. It is used in advances stage or in recurrence
• Types include
• Bleomycin
• doxorubicin
• Cisplatin
• Carboplatin
• Fluorouracil (5-FU)
• Paclitaxel (Taxol®)
• Docetaxel (Taxotere®)
• Irinotecan

• two or more chemotherapy drugs together if you have advanced vaginal cancer.
• You usually have treatment once every 3 or 4 weeks with a break afterwards.
• This makes up a cycle of chemotherapy.
• Most people have a course of about 6 treatments or cycles.
Mainly used drugs
• Doxorubicin(adriamycin)
• 50 mg/m2/iV weekly. Repeat every 3-4 weeks
• S.E-bd, alopecia, cardiac toxicity, myopathy, stomatitis
• Precautions: avoid in significant heart disease, ECG monitoring

• Bleomycin
• 10–12 mg/m2/IV/IM weekly
• S.E:
• skin: hyperpigmentation,ulceration, alopecia.
• Pulmonary: pneumonitis,fibrosis, dyspnea
• Precaution:avoid in renal or pulmonary disease
• Radiation therapy is widely used as a primary treatment for invasive
vaginal cancer.
• Teletherapy (external radiation) reduces the tumor volume and
sterilizes the regional (pelvic and inguinofemoral) lymph nodes
• Complications of radiotherapy include vaginal stenosis, bladder and
rectal fistula.
• Cure rate: Overall 5-year survival rate ranges from 80 percent for
stage I disease to 10 percent for stage IV disease.
Uterine sarcoma
• Classification of uterine sarcomas(gynecologic oncology group)
• Leiomyosarcomas
• Endometrial stromal sarcomas
• Malignant mixed müllerian tumor (homologous and heterologous)
• Other uterine sarcomas.

• Chemotherapy is used as an alternative to radiotherapy in uterine

sarcoma.
• Stage I Uterine Sarcoma
• Treatment of stage I uterine sarcoma may include the following:
• Surgery (total abdominal hysterectomy, bilateral salpingo-oophorectomy, and lymphadenectomy).
• Surgery followed by radiation therapy to the pelvis.
• Surgery followed by chemotherapy.

• Stage II Uterine Sarcoma

• Treatment of stage II uterine sarcoma may include the following:
• Surgery (total abdominal hysterectomy, bilateral salpingo-oophorectomy, and lymphadenectomy).
• Surgery followed by radiation therapy to the pelvis.
• Surgery followed by chemotherapy.

• Stage III Uterine Sarcoma

• Treatment of stage III uterine sarcoma may include the following:
• Surgery (total abdominal hysterectomy, bilateral salpingo-oophorectomy, and lymphadenectomy).
• A clinical trial of surgery followed by radiation therapy to the pelvis.
• A clinical trial of surgery followed by chemotherapy

• Stage IV Uterine Sarcoma

• There is no standard treatment for patients with stage IV uterine sarcoma. Treatment may include a clinical trial using
chemotherapy.
• Adjuvant chemotherapy is the mainstay of treatment of advanced or recurrent
ULMS.
• Choices of chemotherapy
• Doxorubicin(adriamycin)
• Anthracycline antibiotic with antineoplastic activity
• Prevents DNA replication and inhibit protein synthesis.
• Inhibits topoisomerase 2
• 50 mg/m2/iV weekly. Repeat every 3-4 weeks
• S.E-bd, alopecia, cardiac toxicity, myopathy, stomatitis
• Precautions: avoid in significant heart disease, ECG monitoring

• Vincristine(oncovin)
• A plant derivative
• 0.4–1.4 mg/m2 IV weekly
• S.E: paresthesia, weakness, loss of reflexes, foot drop, bone marrow depression,
reticulocytopenia, alopecia, hoarseness, anemia
• Precautions:avoid extravasation, dose adjustment with liver disease
• Cyclophosphamide
• Alkylating agent
• 750–1,000 mg/m2 of body surface/IV. Single dose every 3 weeks.50–110 mg/m2 by mouth (PO)
• S.E:bone marrow depression (bd) alopecia, cystitis
• Precaution:adequate fluid intake

• ifosfamide (ifex)
• An alkylating agent
• 7-10 gm/m2 IV over 3–5 days, to be repeated every 3–4 weeks
• S.E-alopecia, bone marrow depression, cystitis
• Precautions-uroprotectant

• New treatment involves combination use of gemcitabine and docetaxel. Highly effective in
leiomyosarcoma that has metastasized and cannot be surgically removed.

• Prognosis
• The prognosis is unsatisfactory. The 5-year survival rate ranges from 10–30 percent
 CHEMOTHERAPY IN VULVA
CARCINOMA AND
GESTATIONAL
TROPHOBLASTIC NEOPLASIA
PRESENTED BY FARDEENA BEGAM BAIROSKAN
 CHEMOTHERAPY IN VULVA
CARCINOMA :
• The main treatment for vulvar cancer is surgery. If a biopsy shows that vulvar cancer is present and that it
appears to only be in the vulva, for most patients the next step is surgery. Radiation therapy and
chemotherapy may be used if the cancer cannot be entirely removed with surgery, if the cancer has a
high risk of coming back, and/or if the lymph nodes are involved with cancer.

• Surgery and Chemotherapy in main treatment in carcinoma of vulva

• 5 Fluorouracil,mitomycin and cisplastin as radiation sensitizer is effective in treating such patient.
CHEMOTHERAPEUTIC MECHANISM OF INDICATION RELEVANT SIDE
AGENT ACTION EFFECTS
PLATINUM DRUGS Inhibits DNA EOCA, CA Cervix & Nephrotoxicity,Neurot
Cisplatin, Carboplatin replication Endometrium, Vulva oxicity.

ANTIMETABOLITES DNA synthesis Vulval Ca Mucositis

5 Fluorouracil inhibition
EOCA, Cervical CA Peripheral edema
Gemcitabine
GESTATIONAL TROPHOBLASTIC
NEOPLASIA (GTN)
• Gestational trophoblastic disease (GTD) is a group of rare diseases in
which abnormal trophoblast cells grow inside the uterus after
conception.

• Hydatidiform mole (HM) is the most common type of GTD.

• Gestational trophoblastic neoplasia (GTN) is a type of gestational

trophoblastic disease (GTD) that is almost always malignant. It includes :-
• Invasive moles
• Choriocarcinomas
• Placental-site trophoblastic tumors
• Epithelioid trophoblastic tumors
• The diagnosis of GTN does not require histopathology. Diagnosis is made
solely with serum testing of hCG levels.

The diagnostic criteria for a GTN are:

A plateau (+/- 10%) in hCG levels over at least 3 weeks (i.e. 4 consecutive values);
• A rise (≥ 10%) in hCG levels over at least 2 weeks (i.e. 3 consecutive values);
• Persistence of hCG at ≥ 6 months after molar evacuation
• Histologic evidence of choriocarcinoma
• Presence of metastatic disease
STAGING:

Staging : FIGO 2000 Anatomical staging

CHEMOTHERAPY:
• Blood counts+liver function tests+kidney function test daily
• X ray chest repeat only if HCG titres plateaus or rises.
• Serum HCG weekly
• Treatment should not be repeated if
 wbc <3000 cu mm
 Polymorphonuclear leucocytes <1500 cu mm
 Platelet count <1 lakh /cu mm
 Significant elevation of BUN,SGPT

Continue treatment at 1 to 3 weekly interval until 3 consecutive negative weekly HCG titres.
Continued for consolidation phase of six to 8 weeks after normalisation of HCG levels.
INDICATION OF CHEMOTHERAPY IN
GTD
• 1.Histological e/o of choriocarcinoma
• 2.E/O metastasis in brain ,liver ,GIT or radiological opacity > 2 cm on CXR.
• 3.Pulmonary,vaginal or vulva metastasis unless HCG levels are falling
• 4.Heavy vaginal bleeding with E/O GIT or Intra peritoneal perforation.
• Rising HCG after evacuation
• Serum HCG >20,000 more than 4 weeks after evacuation
• Elevated HCG six months after evacuation even if falling
• For the GTN is scored to be low risk (score 6 or less ) :
monotherapy – methotrexate and folinic acid rescue.

• For the GTN is scored to be high risk (score 7 or more ) :

multidrug chemotheraphy (EMA-CO regimen)
EMA : etoposide, methotrexate and dactinomycin.
CO : cyclophosphamide and vincristine.
EMA alternates with CO every week.

• Such women will receive methotrexate (50mg IM every 48 hours for 4 doses) with
calcium folinate (folinic acid) rescue (15mg orally 30 hours after methotrexate).

• Courses are repeated every 2 weeks and prognosis is almost

100%.
• Side effects are mucosal ulceration and conjunctivitis.
• Hair loss is not seen in this regimen.
• The EMA-CO regimen is recommended for high-risk cases given
every 2 weeks.
• The treatment causes reversible alopecia and is myelosuppressive.
• Cumulative 5-year survival of patients given EMA-CO is between
75 to 90%.
• Post-chemotherapy follow-up :

After conclusion of chemotherapy, hCG estimations are weekly

until 6 consecutive normal results ( < or equals 2 iu/L )
Then every fortnight until a further 8 normal results and then
monthly
REFERENCE
1. https://www.cancer.org/cancer/endometrial-cancer/treating/chem
otherapy.html
2. https://www.cancer.org/cancer/cervical-cancer/treating/chemother
apy.html
3. https://www.cancer.net/cancer-types/cervical-cancer/types-
treatment
4. DC DUTTA TEXBOOK OF GYNAECOLOGY
5. https://www.jogc.com/article/S1701-2163(15)30999-3/fulltext#