Cisplatin

Cisplatin is a prescription drug used in the treatment of cancers of the ovary, bladder and testes. The drug is given by intravenous injection, and is also known by its brand name Platinol.

What is Cisplatin and Where does it Come From?

Cisplatin, or CDDP¹, is an inorganic compound consisting of a platinum atom (Pt) bound to two chlorides (Cl) and two ammonia molecules (NH₃). Cisplatin is a square planar molecule, which means that it truly is the shape shown below as opposed to being tetrahedral, or pyramid-shaped. This is important as it means that the two chlorides are right next to one another.

		NH3
		|
Cl	—	Pt	—	NH3
		|
		Cl

The compound was first synthesised by M Peyrone in 1884 and is therefore also referred to as Peyrone's Chloride. However, it wasn't until the 1960s that the potential of Cisplatin was noticed. In 1961, Barnett Rosenberg began an experiment to discover the effect of electric fields on the growth of Escherichia coli, only to find that the bacteria had grown to be hundreds of times longer than normal. A series of investigations led Barnett's group to the conclusion that the platinum electrodes were reacting with the chloride solution, leading to the production of several molecules, including cisplatin. They concluded that cisplatin was stopping the bacteria from dividing but not affecting their growth, suggesting a possible role for cisplatin in cancer chemotherapy. Tests on mice confirmed this, and the drug was eventually approved for use in 1978.

What Does it do and Why?

Each of the chlorides in cisplatin can be replaced by a water molecule, which can then be displaced by binding to a nitrogen on a nucleotide in RNA or DNA. As there are two chlorides, the drug can react with the two strands of DNA, cross-linking them so that they can't split apart during DNA replication or to allow the production of RNA. This has the effect of killing and interfering with the growth of tumour cells while also increasing their susceptibility to genetic damage from radiation.

The Side Effects of Cisplatin

Contrary to popular belief, all drugs do in fact have a range of other possible effects, as they don't just affect their intended target. This is especially true of cisplatin as it targets every cell in your body, with the dose required to kill the patient being just greater than that required to kill the tumour cells. The following side effects are therefore sometimes seen:

• Bone marrow toxicity, leading to a depressed immune system.
• Nephrotoxicity, causing damage to the kidneys.
• Neurotoxicity, sometimes leading to deafness.
• Impaired wound healing.
• Alopecia (hair loss) due to damage to the hair follicles.
• Damage to the gut lining, leading to problems absorbing nutrients.
• Severe nausea and vomiting.
• Sterility caused by damage to normal ovary or testes cells.
• Teratogenicity

Cisplatin is also known to cause specific damage to the kidney and peripheral nervous system. Due to the toxic nature of cisplatin, it is important that patients on the drug look out for various warning signs, which indicate that they should notify their doctor immediately:

• Shortness of breath or wheezing.
• Swelling of the feet or ankles.
• Dizziness and/or fainting.
• Seizures or fitting.
• Fever or chills.
• Black, tar-like stools².
• Abnormal bruising or bleeding.

When and How is Cisplatin Used?

Cisplatin can be used to treat a variety of tumours including carcinoma of the head and neck, lungs, breast, bladder and adrenal cortex³, but is most effective in the treatment of germ cell⁴ cancers of the testes and ovary. It also has a use in the treatment of mesothelioma.

Cisplatin is given intravenously for up to five days followed by a break of two or three weeks - this is known as one cycle of treatment. Patients are often given diuretics and encouraged to drink plenty of fluids in order to dilute the toxic effects of cisplatin as it passes out through the kidneys, and the nausea and vomiting caused by the drug can be controlled to a certain extent by antiemetics. The patient's hearing and kidney function are often tested in between cycles. The drug may also be used to flood the cavity left after removal of a tumour to ensure that all the remaining tumour cells are killed.

Combined Treatment

Cisplatin may be given with other anti-cancer drugs as this can decrease the survival rate for some cancers. The rationale behind combined therapy is that if a tumour cell develops resistance to one of the drugs, the other(s) will kill it. Also, some drugs are more deadly to cells at the edge of the tumour where the blood supply is good, and need to be combined with drug which kills those inside the tumour. Cisplatin may also be combined with radiotherapy, as the drug tends to sensitise the tumour cells to radiation.

Should I be Taking Cisplatin?

This is something for a trained professional to decide, as the risks will outweigh the benefits if the drug is taken needlessly. Anti-cancer drugs are not a magical cure-all for all the cancers in the world and each specific cancer needs different treatment, and so cisplatin is not the right drug for everyone.

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¹ CDDP stands for cis-diamminedichloroplatinum (II).
² Another word for poo.
³ Part of an important gland that sits just above the kidney.
⁴ Eggs and sperm.