Cisplatin

Quick Summary

Cisplatin is a platinum-based drug, first discovered by a scientist named Michele Peyrone in 1845. At the time, cisplatin was called Peyrone’s salt or Peyrone’s chloride, but its cancer-fighting properties weren’t fully recognized until 1969.

What is Cisplatin?

Cisplatin is a chemotherapy drug that sometimes goes by the generic name CDDP, or the brand names Platinol and Platinol-AQ. Cisplatin is one of the standard drugs used in the treatment of mesothelioma, as well as numerous other forms of cancer.

In the late 60’s, Barnett Rosenberg accidentally discovered platinum’s ability to disrupt the division of cells like cancer. He was researching cells in magnetic fields when he observed that cells charged by platinum electrodes no longer divided. He initially blamed the magnetic field but later concluded it was the platinum that disrupted the cells, and accurately predicted its ability to fight tumors.

In 1978, the FDA approved use of cisplatin in the treatment of cancer, and it has been a routinely used chemotherapy drug ever since.

How is Cisplatin Administered?

Cisplatin is injected into the bloodstream through an intravenous drip. Medical staff will place a small tube into the patient’s vein, which is then connected to a bag that will drip cisplatin and any other chemotherapy drugs being administered.

In some rare cases, cisplatin may be administered through a central line. A central line connects directly to a larger vein in the chest or arm and is used when an IV isn’t possible within the smaller veins that are typically used.

Cisplatin can be prescribed in a variety of cycles, ranging from every 3 or 4 weeks to once per week.

How Does Cisplatin Treat Mesothelioma?

Cisplatin treats mesothelioma by targeting cancer cells and disrupting their ability to properly divide.

Cancer is caused by cells that grow abnormally, dividing and multiplying at rates that are too fast for the body to control. While normal cells stop reproducing when they come into contact with other cells, cancer continues to multiply and grow together, resulting in the masses commonly referred to as tumors.

Cisplatin works by preventing cancer cells from being able to multiply. It finds cells that are dividing at abnormal rates and then disrupts the DNA that gives cells their reproductive instructions. Cells that can’t divide are forced into apoptosis, or “cell suicide.” Simply put, cisplatin damages the cells’ DNA and forces them to die.

However, cisplatin and other chemotherapy drugs aren’t able to tell the difference between cancer cells and healthy cells. As a result, it’s quite common for red and white blood cells to also get destroyed during chemotherapy. Smart drugs attempt to resolve this with the development of drugs that will properly identify cancer cells, but this form of mesothelioma treatment is still undergoing testing and trial.

Cisplatin Drug Combinations

Cisplatin is often combined with pemetrexed, also called Almita, because of their proven ability to complement one another. Clinical trials have proven that the two drugs together have better outcomes than either drug on their own. Patients who receive cisplatin and pemetrexed are often required to take folic acid supplements and steroid tablets and receive vitamin B12 injections.

Cisplatin has also been researched in combination with gemcitabine, which has proven equally effective to cisplatin and pemetrexed. However, cisplatin and gemcitabine has stronger side effects in patients and is more challenging to administer. As a result, oncologists favor combining cisplatin with pemetrexed instead of gemcitabine whenever possible.

Cisplatin can also be combined with vinorelbine, known under the trade name Navelbine, a chemotherapy drug derived from periwinkle plants.

Current Cisplatin Clinical Trials

Cisplatin and pemetrexed is currently recognized as the best chemotherapy combination for mesothelioma and some other forms of cancer. As a result, cisplatin and pemetrexed are often used as a baseline when evaluating the efficacy of new chemotherapy drugs and other cancer therapies.

One Phase III clinical trial underway is comparing cisplatin and pemetrexed against a combination of targeted drugs called nivolumab and ipilimumab. These two targeted drugs interrupt the signal pathways that instruct cells how to behave, ultimately immobilizing the cancer cells. Unlike chemotherapy, which targets any cell that multiplies too quickly, targeted drugs seek out specific genetic markers that are only found in mesothelioma or other cancer cells. Many pharmaceutical companies and research centers are investing in these alternative therapies, as they could help fight and potentially cure cancer, with fewer patient side effects.

In addition, several current clinical trials are researching the maximum dosage of cisplatin that can be used in hyperthermic intraperitoneal chemotherapy (HIPEC). Also referred to as heated chemotherapy, HIPEC is a process in which the abdomen and organs are soaked in a warm chemo solution after a surgical operation, directly targeting any of the microscopic mesothelioma cells left behind. Surgical oncologists are attempting to find out exactly how much cisplatin can be placed directly into the body without causing excessive harm to mesothelioma patients.

Because of its powerful effects against cancer and its long history of use, cisplatin has been involved in hundreds of clinical trials, many of which have focused on mesothelioma patients.

Cisplatin Side Effects

Cisplatin is an effective but highly toxic chemotherapy drug. As a result, mesothelioma patients often experience unpleasant side effects, and the monitoring for these can be quite rigorous. Patients who are receiving cisplatin are also likely to have regular blood work to check blood and electrolyte levels, as well as general organ function.

Physical examinations and hearing tests are also performed periodically to check reflexes for specific symptoms that may indicate the cisplatin dosage is too high. In fact, it’s quite common for oncologists to adjust a patient’s cisplatin dose, as they attempt to appropriately balance benefits with side-effects.

The most common side effects of cisplatin are nausea and vomiting for up to one week after treatment, decreased white and red blood cell counts, temporary kidney toxicity, hearing loss or ringing in the ears, and low magnesium, calcium, or potassium levels. These side effects occur in more than 30% of patients who receive cisplatin.

The lowered red and blood cell counts can lead to other side effects, including infection, anemia, or excessive bleeding. This side effect typically peaks between 18 to 23 days after the initial treatment, with cell counts returning to normal 39 days after treatment ends.

Less common side effects for cisplatin, occurring in 10 to 29% of patients receiving the drug, include loss in appetite, metallic taste in the mouth, hair loss, an increase in liver function, and peripheral neuropathy.

Peripheral neuropathy occurs when a patient loses feeling or sensation in their arms or legs. Though not as common as the other side effects, peripheral neuropathy is a serious condition that progressively worsens with treatment. In some cases, patients may find it difficult to move or walk, and the oncologist may lower the cisplatin dose. Modifying cisplatin doses is particularly important when these symptoms are present, as peripheral neuropathy can be irreversible.

Cisplatin is recognized as an aggressive treatment option and is often the first choice for mesothelioma patients. However, the severity of side effects means it’s not right for everyone. Carboplatin was developed as an alternative to cisplatin, sharing many of the benefits but with lesser impacts. Patients are often prescribed carboplatin over cisplatin if they are older, have other health concerns, or are allergic to cisplatin.

If you’ve been diagnosed with mesothelioma, contact one of our Support Experts today to find out more.

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Sources
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  7. U.S. National Library of Medicine. “Study of Nivolumab Combined With Ipilimumab Versus Pemetrexed and Cisplatin or Carboplatin as First Line Therapy in Unresectable Pleural Mesothelioma Patients (CheckMate743).“ Retrieved from https://clinicaltrials.gov/ct2/show/NCT02899299?term=cisplatin&cond=Mesothelioma&draw=3&rank=24. Accessed on January 24, 2018.
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Last modified: May 7, 2018