Side Effects of Carboplatin
Carboplatin is less chemically reactive than cisplatin,
which is why it is less toxic to the kidneys and nervous system.
The downside is that the lower reactivity means a higher concentration
is needed to fight the cancer, and bigger doses of the drug. It
is estimated that carboplatin is 8 to 45 times less effective
than cisplatin.
The most troubling effect of carboplatin tends to
be damage to the bone marrow, in a process called myelosuppression.
This leads to anemia. Blood cells produced by the marrow can drop
to 10% of normal levels. This level bottoms out a few weeks after
carboplatin administration.
Other reported side effects:
- loss of appetite or weight
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stomach pain
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diarrhea
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constipation
- peripheral neuropathy
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changes in vision and taste
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These are common side effects of many chemotherapy drugs, especially
the alkylating
agents. Carboplatin also is known to damage the kidneys (it
is nephrotoxic) and the inner ear (in a process called
ototoxicity.)
Nausea and vomiting can be severe in some patients, and antiemetic
drugs are often given.
Neoplasms, especially consisting of certain cell types, are known
to develop resistance to alkylating agents. This resistance has
been linked, at least in part, to the expression of an enzyme
known as MGMT (O6-MethylguanineDNAmethyltransferase). MGMT is
able to repair DNA errors caused by alkylating agents. For example,
temozolomide causes a potentially cytotoxic lesion in oxygen 6
of guanine nucleotides in DNA. MGMT enzymatically removes this
methyl group, repairs the DNA, and negates the effect of the chemotherapy.
In normal cells this would be advantageous; a cellular mechanism
to prevent DNA disruption in cells that are normal physiologically.
However cancers are also able to express this protein (and perhaps
even overexpress it) thus rendering certain alkylating agents
ineffective. Drugs that inhibit MGMT activity may be used as an
adjunct to alkylating agents in order to overcome this resistance
and improve the tumor-killing effect.
Prolonged exposure to alkylating agent can result in up to 10
to 15 fold increase in resistance. Studies have shown this is
due to a response by the body resulting in higher glutathione
and metallothionein levels. Metallothionein is a protein that
binds to heavy metals and rises when metal levels in the blood
are elevated.
In general, chemotherapy drugs can be broken down by enzymes
outside any cells and by nonmalignant cells near the tumor. This
degrades the action of the chemotherapy agent.
The size of a tumor can influent the efficacy of the drug. Larger
tumors are more difficult for the drug to penetrate, and also
more difficult for nutrients and oxygen to get to the interior
cells of the tumor (indeed, this is the idea behind angiogenesis
inhibitors – cutting off the growth of capillaries that serve
the tumors.)
Oncologists have long known that faster-growing tumor respond
more favorably to anticancer drugs that slower-growing ones. For
instance, testicular cancer tumors double in size every 21 days
while colon cancer tumors double every 95 days and pulmonary adenocarcinoma
tumors double every 154 days.
The growth rate of a tumor is at a maximum when it is at 37%
of its maximum (limiting) size.
The limiting toxicities for the platinum drugs tend to be renal
– they cause acute tubular necrosis. They can also cause secondary
cancers. Ototoxity (ear drum damage) is also a possibility.
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