Professional Documents
Culture Documents
By
Dr Dambo
Introduction
• Chemotherapy:- the treatment of disease
or infection with chemicals or drugs
• Effective chemotherapy for gynaecological
cancers exploits xteristic differences b/w
tumour cells and normal cells to
selectively kill malignant cells without
producing serious, irreversible harm to
vital organs and tissues.
• Research in molecular biology and cell kinetics,
has improved knowledge on the scientific basis
of cancer chemotherapy, which is serving in the
development of new drugs, establishment of
more rational protocol basic for the design of
protocols, the optimal use of the presently
available drugs.
• Long-lasting remissions and occasional cures
for several types of cancer have been achieved
with antitumour drugs. E.g up to 90% of patients
with metastatic choriocarcinoma achieve a
normal life expectancy, and almost 100% of
those without metastases are cured now.
• The effect of the drugs may be monitored
by the level of Beta-hCG which provide a
reliable index of tumour growth.
• The use of cytotoxic drugs for Ca of the
Cx vagina and vulva is still on clinical trial
basis, since this tumours usually grow
more slowly, and cytotoxic drug treatment
has been palliative but not curative;. these
types of cancer are better controlled by
surgery and radiation therapy, and
chemotherapy should be considered only
when these standard methods have
proved ineffective
• Among the uncommon gynaecological Ca
that may require chemotherapy are germ
cell tumours of the ovary, uterine, vaginal
or vulvar sarcomas. Because these
tumours are rare, little is known about
there sensitivity to antitumour drugs.
Normal cell cycle
• Go: resting phase (cell not committed to division)
• G1 enzyme produced necessary for DNA production (18 hours)
• S: DNA synthesis (20hours)
• G2: specialized protein and RNA synthesis (3hours)
• M: mitosis (1hour)
Cell Kinetics
• Cell kinetics is helpful in understanding the
dynamics of tumour cells, in which some
cells divide more slowly than others some
cells enter or leave a nondividing state,
and some are lost from the tumour
population entirely.
• The MITOTIC INDEX (MI) is the fraction of
cells in mitosis in a steady-state.
• GROWTH FRACTION (GF) is the overall
proportion of proliferating cells in a given
tumour
• CELL CYCLE TIME denotes the amount
of time needed by a proliferating cell to
progress through the cell cycle and
produce a new daughter cell.
• DOUBLING TIME is the time required for
the tumour cell population to double.
Effects on chemotherapy on the
cell cycle
• The effects of various classes of anticancer
agents on tumours depend on the basic events
occurring in the 4 main phases of the cell cycle
and the pharmacologic mechanisms of the drug
action, and these cytotoxic effects influence the
design of rational drug regimens.
• Two basic classes of antineoplastic drugs are
recognised:
-Cell cycle(phase) specific agents
-Cell cycle(phase) non-specific agents.
• CELL CYCLE SPECIFIC drugs: lethal to cells
only during a reproductive phase.
• More effective in tumours in which a large
proportion of cells are actively dividing , as
occurs when the cell mass is low.
• They produce a greater kill, if given in multiple,
repeated fractions rather than as a large single
dose.
• Drugs include:
-methotrexate/fluorouracil: s phase
-corticosteroids/asparaginase: G1 phase
-bleomycin: G2 phase
-vinca alkaloids: M phase
• CELL CYCLE NON SPECIFIC drugs:- are able
to sabotage the cells no matter what
phase they are in.
• Are effective in large tumours in which the
growth fraction LI and MI are low.
• Drugs in this group are dose dependent, since a
single bolus injection generally kills the same
number of cells as do repeated doses totaling
the same amount ie, the degree of cell kill is
directly proportional to the absolute dose given
• Drugs include:
-Alkylating agents
-Nitrosoureas
-Antibiotics
Nitrosoureas
Cellular differentiation Carmustine
Of clones Go Resting
Stem cell
(Recruitment)
1. Vinca alkalloids
(vincristine, vinblastine)
2.Taxanes (paclitaxel) 1. steroids?
3. Podophyllotoxins 2. Asparaginase Cell cycle(phase)-non specific agents
(etoposides) 3. diglycoaldehyde
18hrs
G1
• Alkylating agents
1 hr
(cyclophosphamide, busulfan,
chlorambucil)
Stem • Anthracycline antibiotics
cell
3 hrs G2 (doxorubicin, dactinomycin)
• Miscellaneous (cisplatin,
S carboplatin)
20 hours