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
• stomach pain
• diarrhea
• constipation
• peripheral neuropathy
• nausea and vomiting
• changes in vision and taste
• mouth blistering
• fatigue
  

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.

Chemotherapy drugs as hazardous materials

Many oncology drugs are hazardous. The National Institute for Occupational Health and Safety (NIOSH) has even issued regulations and guidelines for healthcare workers who handle chemotherapy agents.

The Institute for Safe Medication Practices (ISMP) lists Carboplain among drugs which have a heightened risk of causing significant patient harm when used incorrectly.