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GENERAL

PRINCIPLES
OF
ANTICANCER
THERAPY
Edalyn R. Capili
Metropolitan Medical Center
College of Medicine

CAUSES OF CANCER
Sex, Age, Race, Genetic Predisposition
Exposure to environmental carcinogens
Ionizing radiation
Chemical carcinogens
HBV and HCV - Hepatocellular cancer
HIV - Hodgkins and non-Hodgkins lymphomas
HPV - Cervical cancer; Anal and Penile cancers;
and Oropharyngeal head and neck cancer
HHV-4 - Nasopharyngeal cancer, Burkitts
lymphoma, and Hodgkins lymphoma

CANCER TREATMENT
MODALITIES
Primary
chemotherapy
primary
treatment in patients who present with
advanced cancer for which no alternative
treatment exists.
Neoadjuvant chemotherapy - in patients
who present with localized cancer for which
alternative local therapies (surgery), exist
but which are less than completely
effective.
Adjuvant chemotherapy - after surgery
has been performed, and the goal is to
reduce incidence of both local and systemic
recurrence and to improve overall survival

THE CELL CYCLE


Phase that precedes DNA
synthesis (G1)
DNA synthetic phase (S)
Interval
following
the
termination of DNA synthesis
(G2)
Mitotic phase (M) in which the
cell,
containing
a
double
complement of DNA, divides
into two daughter G1 cells
Probability of moving into a
quiescent state (G0) and failing
to move forward for long
periods of time

THE CELL CYCLE


At each transition point in the cell cycle, p53
and chk-1 and 2, monitor the integrity of
DNA and, upon detection of DNA damage,
may initiate DNA repair processes or, in the
presence of massive damage, direct cells
down a cell death (apoptosis) pathway.
Each transition point requires activation of
CYCLIN-DEPENDENT
KINASES,
which
couple with corresponding regulatory proteins
called CYCLINS. The proliferative impact of
CDKs is in turn dampened by p16.
Tumor cells often exhibit changes in cell-cycle
regulation that lead to relentless proliferation.

GENERAL PRINCIPLES
Single clonogenic cell is capable of
producing progeny that kill the host.
The proliferation rate of cancer cell is
different from normal cell. Cytotoxic
drugs kill cancer cells by First Order
Kinetics.
Combined modality approach can be
used for cancer therapy.
Poly pharmacy can be used to
achieve TOTAL TUMOR CELL KILL.

GENERAL PRINCIPLES
Cytotoxic drugs are either cell
cycle nonspecific or cell cycle
specific.

Cell cycle nonspecific kill


resting as well as dividing
cells.
Cell cycle specific kill only
actively dividing cells.

Mechanisms and Sites of


action of some
Chemotherapeutic Agents
useful in Neoplastic
Disease

CELL CYCLE KINETICS


& ANTI-CANCER
EFFECT

Log-kill hypothesis
Dashed line no tx
given.
Arrows

tx
given
infrequently, result is
manifested
as
prolongation of survival
but with recurrence of
sxs between courses of
tx and eventual death
of the patient.
Inverse
relation

ROLE OF DRUG
COMBINATIONS
Efficacy: Somewhat effective when used alone against
tumor should be selected for use in combination.
Toxicity: Does not overlap with the toxicity of other
drugs in the combination.
Optimum scheduling: Used in optimal dose and schedule,
and drug combinations should be given at consistent intervals.
Mechanism of interaction: Clear understanding of the
biochemical, molecular, and pharmacokinetic mechanisms of
interaction to allow for maximal effect.
Avoidance of arbitrary dose changes: May reduce dose of
the most effective agent below threshold of effectiveness.

DOSAGE FACTORS
Dose intensity is one of the factors limiting ability of
chemotherapy or radiation therapy to achieve cure.
For chemotherapy, therapeutic selectivity is
dependent on the difference between dose-response
curves of normal and tumor tissues.
3 approaches to dose-intense delivery of
chemotherapy:
Dose escalation
Reducing the interval
Sequential scheduling

DRUG RESISTANCE
Primary/Inherent Resistance
absence of prior exposure to
available standard agents
Acquired Resistance
develops in response to exposure
to a given anti-cancer agent

CAUTIONARY NOTE
The
pharmacokinetics
and
toxicities of cancer drugs vary
among individual patients.
It is imperative to recognize
toxicities early, to alter
doses
or
discontinue
offending
medication
to
relieve
symptoms
and
reduce risk, and to provide
vigorous supportive care.

You were given this life


because you are STRONG
ENOUGH to live it!

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