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INTRODUCTION.
EPIDEMIOLOGY AND ETIOLOGICAL FACTORS.
HISTORY OF DEVELOPMENT AND CLASSIFICATION.
PHARMACOKINETICS AND INNOVATION OF NEWER
AGENTS.
INTERFERENCE AND MECHANISM OF ACTION OF
ACTION ARRESTING IMMATURE CELL PROLIFERATION.
AGENTS WHICH POTENTIATE THE FUNCTION OF
CHEMOTHERAPEUTICAGENTS.
CLINICAL APPLICATION AS PRIMARY TREATMENT AND
AS ADJUVANT IN MALIGNANTLESIONS.
DRUGSENSITIVITY TO VARIOUS LESIONS AND
THERAPYREGIMES.
ROUTES OF ADMINISTRATION OF VARIOUS
CHEMOTHERAPEUTICAGENTS.
MARKERS USED TO INTERFERE WITH CELL GROWTH
TO STUDY THE PERFORMANCE OF THE DRUG.
INTRODUCTION
Malignancies of the head and neck region includes cancer of
the oral cavity; i.e., of the lip (International Classification of
Diseases, ninth revision (code140-ICD9:140), tongue (ICD9:141),
and other intra-oral sites (ICD9: 143-145). The salivary glands
(ICD9:142) are not normally included when describing oral
cancer, i.e., of the oropharynx (ICD9:146), nasopharynx
(ICD9:147), and hypophaynx (ICD9:148). Malignancies of these
sites are generally clubbed together as head and neck cancer, or
mouth/pharyngeal cancer, or oro-pharyngeal cancer, or sometimes
just oral cancer, because of the common etiological/risk factors
associated with these sites, with the exception of nasopharyngeal
cancers.17
literature
on
chemotherapy
from
its
historical
and
The
Sex
cancer
Lip (140)
Males
Australia, South
13.5
Canada,
12.7
Newfoundland
Spain, Granada
12.0
Females Australia, South
3.2
Thailand, Khon Kaen
2.7
Israel: Jews bone in 1.6
Israel
Tongue (141) Males France, Bas-Rhin
8.0
India, Bombay,
6.5
US,
Connecticut: 6.0
Black
Females India,Karunagappally, 3.7
Philippines, Manila
2.1
Mouth (143-
Males
1.6
12.4
0.1
0.2
India, Bangalore
China, Shanghai
US, Puerto Rico
India, Bangalore
0.2
0.0
0.2
0.2
Jaban, Yamagata
China, Tianjin
Poland, Kielce
0.4
0.5
0.8
Belarus
Canada,
0.2
0.4
New
Brunswick
China, Shangai
Peru, Lima
0.5
0.5
5)
Oropharynx
India, Trivandrum,
Italy, Trieste
Females India, Bangalore,
Singapore, India
Philippines, Manila
Males France, Somme
10.8
8.4
8.9
3.6
3.2
13.3
China, Tianjin
Finland
Spain, Zargoza
Japan, Yamagata
China, Tianjin
Israel: All Jews
0.8
1.0
0.2
0.3
0.4
0.3
6.7
5.7
China, Shanghai
Finland
0.3
0.4
1.6
1.0
0.9
15.0
8.3
6.8
China, Shanghai
Belarus
Finland
China, Shanghai
Israel: All Jews
Philippines,
0.1
0.1
0.1
0.1
0.2
0.3
(146)
Slovenia,
US
Connecticut:
Black
Females Switzerland, Geneva
US, SEER: Black
Thailand, Chiang Mai
Hypopharynx Males France, Calvados,
India, Bombay
Switzerland, Vaud
Manila
Females India, Madras
2.4 China, Shanghai
0.0
Switzerland, Vaud
1.0 Finland
0.1
US, Atlanta: Black
0.8 Japan, Miyagi
0.2
Notes: Numbers given are age-standardized (world) annual incidence rates per
100,000 population. Source: Parkin et al.(1997)
SEER: Surveillance, Epidemiology and End Results (Program of NCI, US).
to 0.5 per 100,000; of the oropharynx varies from 13.3 to 0.3 per
100,000; and hypopharynx varies from 15.0 to 0.1 per 100,000.
Lip cancer is particularly common in Australian and Canadian
populations with its incidence in males going up to 13.5 per
100,000. It is not so common in the South-East and East Asian
countries.
The
disease every year, and again, over 80 per cent of these deaths are
from the developing world (Pisani et al., 1993).
Thus, cancer of the head and neck region is an important
cancer globally. For the developing world it is certainly of great
significance, and ranks fourth in frequency. In males, however, it
is the third most common cancer, and in females it ranks fourth
However, in western
The
OUTLINE
CANCER CHEMOTHERAPY
A. Period 1946-1960
OF
DEVELOPMENT
OF
developments
chemotherapy.
in
the
field
of
combination
indication
of
definitive
role
for
adjuvant
chemotherapy.
- Recognition, in long-term survivors, of the late toxicities
of anti-cancer drugs particularly when combined with
radiotherapy.
- Development of the concepts of immunotherapy in man.
Disappointing results despite widespread application.14
Examples
1.Alkylating
agents
Nitrogen
mustard
Chlorambucil
Ifosfamide
Melphalan
Thiotepa
Cisplatin
Carboplatin
II.Antimetabolites
Methotrexate
5-Fluorouracil
Ara-C
Hydroxyurea
Fludarabine
III. Antibiotics
Actinomycin-D
Doxorubin
(Adriamycin)
Daunorubicin
Mithramycin
Mitomycin
Bleomycin
Mitoxantrone
DTIC
M-AMSA
Malignancies Used
in
Lymphomas
Chronic
lymphoblastic
leukemia
Sarcomas
Myeloma
Breast cancer
Ovarian cancer
Head and neck cancer
Breast
and
gastrointestinal
cancer
Acute myeloblastic
leukemia
Chriocarcinoma
Genitourinary cancer
Head and neck cancer
Lymphoma
Acute myeloblastic
leukemia
Germ cell cancer
Gastrointestinal, lung,
Breast cancer
Head
and
neck
cancers
Sarcomas
Lymphoma
Testicular,
breast and
cancers
Lymphoma
Toxicities
Leucopenia
Anemia
Thrombocytopenia
Nausea
and
vomiting
Neurotoxicity
Alopecia
Mucositis
Diarrhea
Leucopenia
Anemia
Thrombocytopenia
Alopecia
Leucopenia,
anemia,
and
thrombocytopenia
Mucositis
Diarrhea
Skin disturbances
Alopecia
Nausea
and
vomiting
Cardiac
and
pulmonary toxicity
lung, Leukopenia
bladder Anemia
Thrombocytopenia
Alopecia
Nausea
Sarcomas
Leucopenia
Acute myeloblastic Anemia
Procarbazine
Hexamethylmel
amine
Asparaginase
leukemia
Thrombocytopenia
Hodgkin;s lymphoma Nausea
Ovarian cancer
Bleeding
Acute lymphoblastic
leukemia
Thorough pharmacokinetic
Immediately
Movement of drug into and out of either compartment is a firstorder process and the rate constants k12, k21, and kel have
dimensions of inverse time (e.g., min-1, hr-1).
A typical two-
INTERFERENCE
AND
MECHANISM
OF
ACTION
General
Chemotherapy is planned on the basis of observed
differences between normal and tumour cells in response to antitumour agents used both as single and in combination. Part of the
difference between normal and neoplastic cells can be emphasized
that cell kinetics cannot explain all the consequences of tumourcell exposure to a drug, since these are also dependent upon
pharmacokinetics, biochemistry and tumour biology.
The proliferation of tumour cells is not entirely autonomous,
neither is it constant; it varies with the size of the tumour and is
related to its blood supply. Animal studies show that the
characteristics of tumour cell proliferation have an important
influence on the response to chemotherapy. Skipper (1971) has
reviewed some of the principles concerned and the following
generalizations can be made for experimental tumours.14|
postsynthetic phase (G2); and (4) mitosis (M) ensues the G2 cell,
containing a double complement of DNA, divides into two
daughter G1 cells. Each of theses cells may immediately reenter
the cell cycle or pass into a nonproliferative stage, referred to as
G0. The cells of certain specialized tissues may differentiate into
functional cells that are no longer capable of division. On the
other hand, many cells, especially those in slow-growing tumors,
may remain in the G0 state for prolonged periods, only to be
recruited into the division cycle again at a much later time. Most
antineoplastic agents act specifically on processes such as the
synthesis of DNA or of the mitotic spindle. Other block the
synthesis of DNA precursors or damage the integrity of DNA.
While most of the known anticancer drugs are G 1 is the period
between mitosis and the beginning of DNA synthesis. Resting
cells (cells that are not preparing for cell division) are said to be
in subphase of G1, G0. S is the period of DNA synthesis; G 2 the
premitotic interval; and M the period of mitosis. Example of cellcycle-dependent anticancer drugs are listed in blue below the
phase in which they act. Drugs that are cytotoxic for cells at any
index
decreases.
The
growth
of
most
the
statistician
who
first
described
the
Note that for both A and B rapidly proliferating cells are more
sensitive than slowly proliferating cells
Predominantly non-phase
dependent
Alkylating agents
Nitrosoureas
Anthracyclines
Imidazole carboxamide (DTIC)
Mitomycin C
Actinomycin D
Predominantly phasedependent
Vinca alkaloids
Hydroxyurea
Cytosine arabinoside
Methotrexate
6-Mercaptopurine
6-Thioguanine
Procarbazine
Podophyllotoxins - VM26
- VPP 16-213
Drug metabolism
Most anti-cancer agents are metabolized in the body, usually
to products which are inactive having lower lipid solubility. These
are then excreted. In some instances, active metabolites are
produced (e.g. cyclophosphamide).
Drug absorption, distribution and excretion
EXCRETION
Biotransformation to
active or inactive
product(s)
A.
Biotransformation
involving
hydroxylation,
animal
model
the
hypoxic
cell
sensitizers
bleomycin.
Chemosensitization by Vasocative Drugs
Several vasoactive drungs can selectively reduced blood
flow and increases the percent of hypoxic areas in experimental
tumor systems.
bioreductive
alkylating
agents
mitomycin
and
impressive.
A new analog, SR-4482 is more toxic than SR-4233 in vitro,
and less toxic in vivo.Several important effects of the
nitroimidazole compounds (hypoxic cytotoxicity, thiol depletion,
and chemosensitization) are felt to be due to reduction of the
parent compound. The benzotriazines are activated by enzymatic
reduction.
plasma
levels
of
10m
IUdR
for
optimal
radiosensitization.
Early clinical trials using the halogenated pyrimidines
demonstrated excessive normal tissue reactions without increased
antitumor efficacy in patients with head and neck cancer. Since
the halogenated pyrimidines are absorbed preferentially in
actively dividing cells, it is not surprising that severe mucosal
toxicity was encountered. Since BUdR is associated with
photosensitivity, recent interest has focused on IUdR.
More
cis-plantinums
When BSO
However, glutathione
Vitamin A is
of
the
most
important
factors
in
selecting
because
of
increased
local
toxicities
seen
with
local
Concurrent
chemotherapy:
The
drugs
are
used
after
surgery
and
before
radiotherapy
(Sandwich)
Sandwich method: Here chemotherapy is administered
after surgery and before delivering radiotherapy.
Various agents have been used either singly or in
combination as chemotherapy. The agents used are Methotrexate,
bleomycin, 5-flurouracil (5-Fu), vinblastine and cisplatinum. The
commonly
used
combinations
being
methotrexate
and
2.
3.
4.
same
chemotherapy
Combined chemo-radiotherapy
Since the late 1960s several efforts were made to commune
chemotherapy with radiotherapy. The concept of combining
chemotherapy and radiation in the treatment of locally advanced
squamous cell carcinoma of the head and neck, particularly
unresectable or inoperable lesions, is attractive.
Many single agents or combinations of drugs were used with
radiotherapy . The most common single agents selected for
combination with irradiation were, hydroxyurea, methotrexate or
bleomycin. The efficacy of these agents combined with radiotherapy
has not been established in randomized oral cancer, which often results
in interruption of therapy.
The search for better and safer agents to combine with
radiotherapy led to the administration of Cisplatin. Cisplatin is an
active agent in squamous cell cancers of the head and neck. It does not
produce mucositis of the oral cavity and should not interfere with the
delivery
of
radiotherapy.
Cisplatin
possesses
properties
of
trails
of
single
agent
chemotherapy
or
died,
or
refused
therapy
respectively.
treatment
options
are
limited.
Traditionally,
dihydrofolate reductase.
to
fluorodeoxyuridine
monophosphate
(5-F-
toxicity
is
myelosuprresion,
specifically
the
1970s,
the
many
trails
using combination
same dose and schedule but have obtained overall response rates,
usually in the range of 25% to 30%, with approximately 10%
achieving a complete response.
Efforts have been made over the past several years to
improve the response rates of the cisplatin 5-FU combination.
Some of this research efforts has focused on (1) substituting the
analogue carboplatin for cisplatin, (2) modulating 5-FU with
leucovorin, and (3) dose escalating the cisplatin combined with
the use of chemoprotectors to try to prevent cisplatin-related
toxicities.
advantage.
toxicity and cost for the patient when compared with single
agents.
Although higher responses and, in particular, complete
responses, can be obtained with the use of cisplatin and 5fluororuacil, more toxicity is noted with this combination than
with single agents.
Primary Chemotherapy
Primary chemotherapy refers to the use of chemotherapy,
given either before local therapy, concurrent, with radiation, or
after local treatment has been completed. The rationale for using
chemotherapy prior to local treatment is based on factors such as
(1) an improved patient performance status, (2) an intact vascular
supply to the tumor bed, and (3) the eradication of
micrometastasis to prevent regional and distant metastases.
Induction (Neoadjuvant)
The initial observation made was that response rates using
single agents, such as cisplatin, bleomycin, and methotrexate,
were higher for patients who had not received prior local therapy
In the 1970s,
treatment
for
nasopharyngeal
carcinoma
carcinoma
is
believed
to
be
These tumors
Chemotherapy has
have shown activity in this disease, but the most active and
frequently
used
are
cisplatin,
doxorubicin,
5-FU,
Miscellaneous groups
A number of diverse histologic tumors present less
commonly in the head and neck area for which chemotherapy has
been
utilized.
These
include
sarcomas,
lymphomas,
rhabdomyosarcomas,
fibrosarcomas,
synovial
particularly
with
doxorubicin-based
rates with chemotherapy are similar to those seen for other sites
and are largely partial response.
Adjuvant
chemotherapy
STAGING
MEDICAL ONCOLOGY
Radiotherapy
and/or surgery
RADIOTHERAPY
Chemotherapy
SURGICAL ONCOLOGY
DENTISTRY
If response to
chemotherapy
If no response to
chemotherapy
No treatment
Hydrocortisone
500mg IV
Hydrocortisone
500mg IV
5FU 500mg IV
Vincristine 2mg
IV
MTX
100mg
IV
MTX
100mg
IV
MTX
100mg
IV
BLEOMYCIN
Folinic acid
15mg
15mg 15mg
15mg
Drugs
Investigator
DeWell (1975)
Richman (1976)
Eisenberger (1980)
BLE, HOU
Huang (180)
Yagoda (1975)
BLE, MTX
Cortes* (1980)
Costanzi* (1976)
Pitman (1979)
MTX, CDP
Livingston (1976)
Kaplan (1979)
Price* (1975)
VCR-Vincristine;
HOU-Hydroxyurea;
MTX-Methodologies
CDp-Cis-diammine
blastine;
dichloroplatinum;
6MP-6
BCG-Bacillus
No.
evaluated
No. with
50%
regression
15
Methotrexate + vincristine
28
15(53%)
Dibromodulcitol + bleomycin
20
5(25%)
Adriamycin + bleomycin
32
11(35%)
Methotreaxate + 5-fuorouracil +
cyclophosphamide + vincristine (modified
COMF)
10
Methotrexate + cyclophosphamide +
vincristine+prednisone (Coopers regimen)
18
4(22%)
13
Methotrexate+6-mercaptopurine + procarbazine
+ chlorambucil + thio-tepe + streptonigrin +
rufochromomycin + vinblastine
82
45(55%)
Drug combinations
Methotrexate + bleomycin
Year
Drug Schedule
No. of
Patients
Response %
CR
Overall
Kish, et al.
30
27
70
Rowland, et al.
21
24
71
Creagan, et al.
20
25
Merlao, et al.
17
Sridhar, et al.
20
17
72
Kish, et al.
18
22
72
Kish, et al.
20
10
20
Merlano, et al.
27
15
59
Dasmahapatra,
et al.
18
11
Amrein,
Waitzman
1985 C 80 mg/m2/24 h d1
5-FU 800 mg/m2 24 h d2-6
39
18
46
Raymond, Cyman
16
Not
Stated
75
Fosser, et al.
21
19
62
Responsea
56
2 CE, 35 improved
150-300mg/dy; then
100-200 mg/day PO
15
2 improved
3 PR, 3 improved
2 excellent and 2
moderate
responses
Improved
1 improved
Chlorambucil
0.2 mg/kg/day X 42
days PO
34
1 CR, 4 PR
Nitrogen mustard
None
0.6mg/kg in 3 divided
doses
41
5 improved
5-FU
15mg/kg/day X 5 IV;
then 7.1mg/kg every
other day until toxicity.
Maximum loading dose
per day, 1,000 mg
84
1 CR, 4 PR, 20
improved
5-FU
2 improved
5-FU
4-8mg/kg/day X 14-42
days
17
3 improved
5-FU
15-20 mg/kg/wk
12
1 CR, 1 PR
Drug
Dose Schedule
Drug
Dose Schedule
Hydroxyurea
80mg/kg q 3 days X 6
wks and 40 mg/kg PO
in 2 divided doses per
day X 21 days;
escalated to 60
mg/kg/day after 21
days if not toxic
Responsea
Evaluable
Patients
1
10
1 improved
3 improved
Vinblastine
0.1 mg/kg/wk to a
maximum of 0.3
mg/kg/wk IV
23
4 PR 7, improved
Procarbazine
150-400mg/day PO or
250-1,250mg single
dose IV
31
3 improved
Adriamycin
60-75 mg/m2 IV q 3
weeks
12
Adriamycin
Review of various IV
dose schedules, i.e., 6090 mg/m2, q 3 weks;
20-30 mg/m2/day X 3, q
3 wks; 0.4mg/kg day 1,
2, 7, 8, 9, 10, q 2 wks; 1
mg/kg/day, q 7 days
and 75 mg/m2: IA over
72h
76
11 PR
Mitomycin C
50mg/kg/day X 6; then
50 mg/kg every other
day until toxicity
Evaluable
Patients
CR +
PR
Response
Rate (%)
Median
Duration
(months)
24
13
23
35
Medenica et al.
Bleo 15 mg IV wk
26
13
50
8.5
(mean)
Vogl and
Kaplan (1979)
31
19
61
CR 7+
Wittes et al.
Treatment
CDDP 2 mg/kg IV q 3 wks
Bleo 0.25 mg/kg IV daily until
toxicity, 1-2 mg daily
maintenance
Moran et al.
(1982)
PR3
17
14
74
24
11
46
26
35
23
15
65
PR3
Pitman et al.
(1983)
MTX 124-250 mg IV
5-FU 600 mg/m2 IV 1h later
CR6
Leucovorin 10 mg/m2 q 6 h X
6 given weekly
Ringborg et al.
(1983)
16
52
Not
available
Investigator
Huang et al.
(1980)
Treatment
Bleo 10 U SCC days 1 and 4
Evaluable
Patients
38
CR +
PR
Response
Rate (%)
Median
Duration
(months)
Jacobs
(1982)
Same as
above:
MTX + 5FU+
leucovorin
30
Vincristine 2 mg IV day 1
33
24
25
16
64
30
21
70
PR6.5
Kish et al.
(1982)
CR11
517
intra-arterial (IA)
intracavitary (IC)
subcutaneous (SQ)
intramuscular (IM)
topical (TOP)
oral (PO)
intravenous (IV)
The following three routes of administration allow for high
drug concentrations in the disease area while minimizing the
systemic concentrations, and thus the side effects:
intrathecal
intra-arterial
intracavitary
Administering chemotherapy intrathecally allows the drugs
to reach the central nervous system to prevent or treat local
disease. The majority of chemotherapy agents do not cross the
blood-brain barrier, so they must be delivered directly into the
cerebrospinal fluid. This is accomplished by either:1) a lumbar
puncture or 2)utilizing an indwelling subcutaneous cerebrospinal
intramuscular
topical
Many of the antineoplastic agents are irritating or damaging
to body tissue, so it is inadvisable to give a subcutaneous or
intramuscular injection of these agents. Some drugs that can be
given by the subcutaneous route are cytosine arabinoside
(ARA-C) and the interferons, while bleomycin and methotrexate
can be given intramuscularly. L-asparaginase is one drug that may
be given either by the subcutaneous or intramuscular route.
Topical
administration has
limited usefulness
with only
vomiting,
or
dysphagia,
the
patients
state
of
the
peripheral
IV
site
for
complications
and
Appropriate
Choice of
Venipuncture Site
forearm
hand
forearm
Satisfactory Vein/Undesirable
Location
hand
Consider central
venous line*
Consider central
venous line*
*In some situations, central venous lines are inserted before the patient is
started on a chemotherapy protocol.
Avoid antecubital
fossa
Needle size
Rationale
Larger veins permit more rapid
infusion and administration of
drugs
Larger veins permit more rapid
circulation of potentially
irritating drugs
Mobility of arm restricted
Risk of extravasation increased
due to patient mobility
Ealry infiltration and
extravasation difficult to assess
due to subcutaneous tissue
Repair of infiltration would be
difficult and debilitating for the
patient
Potentially irritating drugs
reach circulation sooner, with
less irritation to peripheral
veins
Smaller gauge needles less
likely to puncture wall of vein;
less scar tissue at insertion site;
and less pain on insertion
Sequencing of
medications
Particular
intravenous
method of
administration
Silastic Catheters
The Broviac silastic catheter (Davol Inc., Cranston, R.I.)
was first reported in 1973. It was a small-bore, 18-gauge catheter
that as originally described as being safe for infusing Total
Parenteral Nutrition (TPN) on a long-term basis (Simon 1987). In
1979, the larger bored, 16-gauge Hickman catheter (Davol Inc.,
Cranston, R.I.) was reported to be sage for intravenous infusions
including blood transfusions and blood samples (Simon 1987).
The Hickman-Broviac catheters became the front runners for not
only a type of central venous access device but also for a surgical
technique of inserting such catheters. The Hickman-broviac
technique for catheter insertion was designed to reduce an
undesirable complication in the long-term use of these catheters:
infection (Raaf 1985).
Implantable Venous Access Ports (VAPs)
Venous access ports (Vaps) consist of two main features:
the port housing made of either plastic, stainless steel, or titanium
with the resealable silicone septum, and the silastic catheter which
cycle.
prognostic
marker
and
its
association
with
the
perineural invasion.
Agent
A. Alkylating Agents
1. Busulfan (Myleran)
2. Chlorambucil
3. Cyclophosphamide (Cytoxan)
4. Ifosphamide (Ifex)
5. Melphalan (Alkeran)
6. Nitrogen mustard
7. Thiotepa
(triethylenethiophosphoramide)
B. Antibiotics
1. Actinomycin D
(Dactinomycin)
2. Bleomycin (Blenoxane)
3. Daunorubicin (Cerubin)
4. Doxorubicin (Adriamycin)
5. Hexamethylmelamine
6. Mithramycin (Mithracin)
7. Mitomycin C (Mutamycin)
8. Mitoxanthrone (Novantrone)
C. Antimetabolites
1. Amethopterine (Methotrexate)
2. Cytarrabine (Cystar U)
3. Fluorouracil (Adrucil)
4. FUDR (Floxuridene)
5. Hydroxyurea (Hydrea)
6. Mercaptopurine (Purimethol)
7. Thioguaine (Lanvis)
Degree
Mild
Nausea Vomiting*
and
Severe
Moderate
+
++
+
0
+
0
0
+++
+++
0
++
0
0
0
+
0
0
+++
0
++
+++
++
+
+
++++
+++
+++
0
+++
++
+++
+
++
++
0
0
++
++
0
0
0
++++
+
+
+
++
+++
+++
+
++
+++
+++
++
++
++
0
++
+
+
+
0
0
Agent
Agent
D. Nitrosoureas
1. BCNU (BiCNU)
2. Lomustine (CeeNU)
3. Streptozocin (Zanosar)
E. Plant Alkaloids
1. Vimblastine (Velban)
2. Vincristine (Oncovin)
3. VP16 (Etoposide)
F. Platinum Complexes
1. Carboplatin (Paraplatin)
2. Cisplatinum (Platinol)
G. Miscellaneous
1. Aminoglutethamide (Cytadren)
2. L-Asparaginase
3. DTIC (Dacarbazine)
4. Interferon Alpha 2b
5. Mitotaine (Lysodren)
6. Procarbazine (Matuvadex)
7. Tamoxifen (Nolvadex)
Degree
Mild
Nausea Vomiting*
and
Severe
Moderate
++
+++
0
+++
++
+
0
0
++++
++++
0
0
+
0
++
0
0
+++
+++
0
++
++
0
+++
+
+++
0
+
+
+
+
++
++
++
+++
+++
++
0
++
0
+++
+
+
++
0
acid),
somatostatin.
FUDR,
6-mercaptopurine,
mitotane,
and
Treatment
a) Stop oral intake
b) Diphenoxyate with Atropine (lomotil) 1 t.i.d. to .i.d. PO
or loperamide (Imodium) 2 to 4mg q.i.d. PO
c) Patients failing to respond to Lomotil have been reported
by Petrilli et al. to resolve the diarrhea in 24 hours by
having the somatostain analog (Sandostatin) at a dose of
150 g/hr IV.
Stomatitis: Causes =actinomycin D (Cosmogen), amethopeterin,
cyclophosphamide,
cytosine
arabinoside,
daunorubicin,
Peripheral
neuropathy
cisplatin,
carboplatin,
arabinoside,
ifosfamide,
interferon,
mitotane,
ad
procarbazine.
c) Seizures cisplatin, interferon, hydroyurea, procarbazine,
and vincristine.
d) Cerebellar ataxia cisplatin, fluorouracil, and Ara-c.
e) Ototoxicity carboplatin.
f) Retinopathy tamoxifen.
Pulmonary Fibrosis or pulmonary interstitial disease. Causes =
amethopterine, BCNU, bleomycin, CCNU, methyl CCNU,
cytosine arabinoside, and myleran.
Actinomycin,
cyclophosphamide,
daunorubicin,
ulceration
with
extravasation:
Actinomycin
D,
cytosine
DTIC,
arabinoside,
fludarabone,
daunorubicin,
5-fluorouracil,
Amethopterin,
bleomycin,
5-fluorouracil,
CONCLUSION
Despite
BIBLIOGRAPHY
1. Alton Brantely B.: Biology of tumours and Head and
Neck cancer chemotherapy. Laryngoscope.91:11811187, 1986.
2.
Barton,
Gial
M.
Wilker:
Cancer
W.
Needleman:
Basic
principles
of