General Principles
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Factors influencing cancer:
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Environmental carcinogens may
be the most important
-
Chemical carcinogens: implicated
in human and animal cancer--
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Constituents in tobacco
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Azo dyes
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Aflatoxins
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Benzene
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Most carcinogens appear mutagenic
based on the Ames test.
-
Herpes and papilloma group DNA
viruses and type C RNA viruses: implicated in
animal cancer.
-
Oncogenic RNA viruses contain
reverse transcriptase capability, allowing
integration of viral genomic information into the
whole cell.
-
HTLV-1,a particular human T cell
leukemia virus, appears implicated in oncogenesis.
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Certain genes appear to cause
oncogenic transformation -- oncogenes.
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Tumor suppressor genes, when
damaged or lost, may cause neoplastic disease.
Cellular Considerations
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Transformed cells proliferate
abnormally, forming local tumors.
-
Cancer treatment may involve
surgery, radiation, and/or chemotherapy.
-
In 1998,
about half of patients with cancer can be cured
with drug treatment contributing in about 17% of
cases.
-
Cancer chemotherapy can be curative
even in metastatic disease. For example:
-
Certain cancers are more resistant
to current treatment (current drug treatment may
be effectively palliative):
-
Cancer
Cell Burden:
-
Dosing Principles
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Drugs: more
effective in combination (may be
synergistic)
-
More effective if
drugs do not share common mechanisms of
resistance.
-
More beneficial if
drugs do not overlap in major toxicities.
-
Drugs should be in
administered near their maximum
individual doses
-
Drugs should be
administered as frequently as possible --
to maximize dose intensity (dose per unit
time) limiting tumor regrowth.
-
Desirable: maximum
cell kill with each treatment cycle,
using the highest those possible,
repeating doses as frequently as
tolerable.
Salmon, S. E. and Sartorelli, A.
C. Cancer Chemotherapy, in Basic and Clinical
Pharmacology, (Katzung, B. G., ed) Appleton-Lange, 1998,
p. 881-911. |
Calabresi, P. and Chabner, B.A.
Chemotherapy of Neoplastic Diseases. In, Goodman and
Gillman's The Pharmacologial Basis of Therapeutics,(Hardman, J.G,
Limbird, L.E, Molinoff, P.B., Ruddon, R.W, and Gilman, A.G.,eds)
TheMcGraw-Hill
Companies, Inc.,1996, pp.1225-1232. |
Chabner, B.A., Allegra, C.J,
Curt, G.A. and Calabresi, P. Antineoplastic Agents. In,
Goodman and Gillman's The Pharmacologial Basis of Therapeutics,(Hardman,
J.G, Limbird, L.E, Molinoff, P.B., Ruddon, R.W, and Gilman, A.G.,eds)
TheMcGraw-Hill
Companies, Inc.,1996, pp.1233-1286. |
→Anticancer
drugs classes (Click Here)←
→Anticancer
Drug Classes: Adverse Effect Click Here):←
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Myelosuppression
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Myelosuppression: most common dose
limiting toxicity
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Leukopenia
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Thrombocytopenia
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Anemia
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Neutropenia increases infectious complication
risk
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Neutrophil counts less
than 10^9/L with fever
-
Thrombocytopenia: less likely to be dose
limiting than leukopenia
-
Anemia: transfusions not usually
required, except with high-dose
chemotherapy protocols
Reference: Slapak, C.A., and Kufe,
D.W. Principles of Cancer Therapy : In Harrison's
Principles of Internal Medicine 14th edition, (Isselbacher,
K.J., and Braunwald, E., Wilson, J.D., Martin, J.B., Fauci,
A.S. and Kasper, D.L., eds) McGraw-Hill, Inc
(Health Professions Division), 1998, pp. 523-537.
-
Dopamine
Antagonists
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Metoclopramide (Reglan):
-
Dopamine
antagonist (centrally and
peripherally)
-
Parenteral
administration: effectively
reduces nausea and vomiting
associated with the most
emetogenic chemotherapeutic drugs
-
Metoclopramide, in
high doses, can cause
extrapyramidal side effects;
often administered with an
antihistamine (diphenhydramine
(Benadryl)) or a benzodiazepine (lorazepam (Ativan)).
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Serotonin
Antagonists:
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Ondansetron (Zofran); Granisetron
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5 HT3 blockers
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Centrally acting: CTZ
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Peripherally acting: vagus
nerve
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Effective in treating nausea and
vomiting due to cisplatin (Platinol)
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No dystonic reactions (by
contrast to metoclopramide)
Cannabinoids
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Dronabinol
-
Available in oral
formulation
-
Effective against
milder moderate emetogenic agents
or protocols
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Significant mood
alteration; including dysphoric
reactions.
-
Other Agents:
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Alopecia
-
Agents that cause the most
significant hair loss:
-
Cyclophosphamide (Cytoxan)
-
Dactinomycin (Cosmegen)
-
Doxorubicin (Adriamycin, Rubex, Doxil)
-
Paclitaxel (Taxol)
-
Vincristine (Oncovin)
-
ref: Slapak, C.A., and Kufe, D.W.
Principles of Cancer Therapy : In Harrison's Principles of
Internal Medicine 14th edition, (Isselbacher, K.J., and Braunwald,
E., Wilson, J.D., Martin, J.B., Fauci, A.S. and Kasper, D.L.,
eds) McGraw-Hill, Inc (Health Professions Division), 1998, pp.
523-537.
-
Stomatitis
-
Pain relief:
-
ref: Slapak, C.A., and Kufe, D.W.
Principles of Cancer Therapy : In Harrison's Principles of
Internal Medicine 14th edition, (Isselbacher, K.J., and Braunwald,
E., Wilson, J.D., Martin, J.B., Fauci, A.S. and Kasper, D.L.,
eds) McGraw-Hill, Inc (Health Professions Division), 1998, pp.
523-537.
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