Carboplatin

Quick Summary

Carboplatin is a type of chemotherapy drug that’s highly effective for mesothelioma treatment. As an anti-cancer drug, carboplatin stops mesothelioma cells from replicating, which kills them off and slows down cancer growth. Carboplatin if often combined with Alimta—another chemotherapy drug—for optimal treatment effectiveness.

What is Carboplatin?

Carboplatin is a chemotherapy drug often sold under the brand name Paraplatin and Paraplatin NovaPlus. Carboplatin is a derivative of cisplatin and was discovered by Dr. Tom Connors and Dr. Ken Harrap of Michigan State University in the 1970’s. The pair of scientists were funded by the Institute of Cancer Research to create a new chemotherapy drug that had the same benefits of cisplatin but with fewer side effects.

Dr. Connors and Dr. Harrap were successful after testing approximately 300 derivatives and would go down in cancer history for the discovery. The drug received FDA approval in 1989, and the inventors and funding organizations received the Queen’s Award for Technological Achievement in 1991. More than five decades after its initial creation, carboplatin remains one of the most effective chemotherapy drugs, valued for its lower toxicity than cisplatin.

Carboplatin’s primary use is for ovarian cancer, which often spreads through the patient’s abdominal cavity when metastasizing. Carboplatin is also used to treat mesothelioma and some other abdominal and lung cancers.

How is Carboplatin Administered?

Carboplatin is typically administered intravenously into the bloodstream, through an infusion in the arm. A nurse or doctor will place a small tube into the patient’s arm and hooks the tube up to a chemotherapy drip. This process allows the drug to enter the bloodstream directly. In some cases, a central line will be administered instead of a traditional IV, which allows carboplatin to be administered to larger veins. Patients who receive central lines will typically keep them in for the duration of their therapy—up to several months.

Carboplatin can also be administered as part of the hyperthermic intraperitoneal chemotherapy (HIPEC) procedure, commonly referred to as heated chemotherapy. HIPEC is a process in which the internal organs are bathed in a chemotherapy solution and is performed after mesothelioma tumors are surgically removed. By soaking the abdomen in carboplatin, the drug can reach microscopic mesothelioma cells that are often left behind after surgery.

Carboplatin’s treatment cycle is typically 21 days. Carboplatin will be administered for approximately one hour on treatment day, with no additional chemotherapy for the next 20 days. At the end of the cycle, a new cycle may begin, once again involving a single-dose treatment for the duration of the treatment cycle.

How Does Carboplatin Treat Mesothelioma?

Carboplatin treats mesothelioma by attacking cancer cells at a genetic level. Mesothelioma occurs when cancer cells multiply throughout the body, and carboplatin attempts to impede that multiplication by altering the cells’ DNA. Cellular DNA is comprised of two individual DNA strands that tell a cell how to behave and multiple. Many anti-cancer agents work by damaging each of those individual DNA strands, which the cells then have to repair. Carboplatin takes that process one step further and cross-links the two damaged strands together, making it significantly harder for the cell to repair itself.

In other words, carboplatin destroys the cancer cells’ ability to reproduce, which then slows down or completely stops its growth within a patient. One of the processes that allows mesothelioma to occur is the cancer’s ability to override natural death cycle and overproduce.

Carboplatin identifies cells that are reproducing at rapid rates and then damages their DNA, forcing them into apoptosis, the process of cells dying off.

However, carboplatin doesn’t only attack cancer cells. Because it seeks out cells that reproduce quickly, it’s notorious for damaging healthy red and white blood cells as well. Fortunately, these cells typically return to their regular levels 28 days after carboplatin is received.

Carboplatin Drug Combinations

Carboplatin is most commonly combined with pemetrexed, often referred to under the brand name Alimta. Carboplatin and pemetrexed have been proven to be more effective in combating mesothelioma than either drug alone, as carboplatin’s platinum base essentially super boosts the positive effects of pemetrexed—an effect called “synergistic”. However, pemetrexed and cisplatin have better results than pemetrexed and carboplatin, and carboplatin is typically only used when a patient may not be able to endure the harsher cisplatin solution.

Carboplatin has also been combined with gemcitabine, a coupling nicknamed “GemCarbo.” Gemcitabine and carboplatin have proven to be as effective as pemetrexed and carboplatin in fighting cancer. However, gemcitabine has a higher toxicity than pemetrexed, which is why most oncologists favor the pemetrexed combination.

Numerous combinations have been tested with carboplatin, including raltitrexed, but no combination has proven better than its pairing with pemetrexed.

Current Carboplatin Clinical Trials

Carboplatin is currently administered in clinical trials for a couple of purposes. In some studies, carboplatin (and sometimes pemetrexed) are used as a baseline to test against new therapies. Because carboplatin is considered one of the better chemotherapy agents to fight against mesothelioma, it makes sense that scientists make comparisons against it when improving chemotherapy drugs and other therapies.

For example, one clinical trial underway is testing the pemetrexed and carboplatin combination alongside TTFields, a device used in alternating electric field therapy. The Phase II study is attempting to determine whether delivering electrical fields to a mesothelioma tumor can help destroy it.

Another Phase II trial is reviewing pemetrexed and cisplatin, with the option to substitute for carboplatin after the first cycle, in combination with durvalumab, an antibody. Durvalumab is a checkpoint inhibitor, which works by blocking molecular interactions required for normal cell growth and death cycles.

A Phase III clinical trial is reviewing carboplatin and pemetrexed in comparison to nivolumab and ipilimumab, a targeted drug therapy that interrupts cell signal pathways that cancers use to debilitate the immune system. By disrupting this inhibition signal, nivolumab and ipilimumab enable the immune system to fight tumors more effectively. This combination is hoped to be a new therapy against pleural mesothelioma.

Carboplatin Side Effects

Carboplatin is often favored over cisplatin, a similar chemotherapy drug because carboplatin has fewer side effects. In fact, some people who take carboplatin don’t experience any side effects at all.

However, carboplatin is still an aggressive cancer-fighting drug, and there are a few side effects that are relatively common. The most common side effects, which are reported in more than 30% of mesothelioma patients taking carboplatin, are vomiting within 24 hours of injection, fatigue, hair loss, changes in taste, abnormal magnesium levels, and low blood cell counts.

Low blood cell counts occur when carboplatin attacks red and white cells, in addition to cancer cells. These cell counts are typically at their lowest approximately 21 days after receiving carboplatin and return to their normal levels within 28 days of receiving the drug.

Several additional side effects have been recorded in 10-29% of patients receiving carboplatin, including abdominal pain, constipation or diarrhea, infection, mouth sores, kidney problems, hearing loss, and abnormal electrolyte and enzyme levels.

Some patients experience peripheral neuropathy, which is a serious but uncommon side effect that results in decreased sensation in the legs or arm. This can present as numbness or tingling, or general lack of sensation, and can worsen as therapy continues. In some cases, patients may have significant challenges walking. If these symptoms occur, the carboplatin dosage may be reduced.

Like many chemotherapy drugs, the timing and severity of carboplatin’s side effects are predictable. Patients who experience side effects of any kind are encouraged to report them to their oncologist, who can provide guidance on normal versus abnormal reactions.

If you’ve been diagnosed with mesothelioma, contact our Patient Advocates today for more information on chemotherapy and other treatment options.

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Sources
  1. Chemocare. “Carboplatin.” Retrieved from http://chemocare.com/chemotherapy/drug-info/carboplatin.aspx. Accessed on January 22, 2018.
  2. Brazilian Journal of Pharmaceutical Sciences. “Carboplatin: molecular mechanisms of action associated with chemoresistance“ Retrieved from http://www.scielo.br/scielo.php?script=sci_arttext&pid=S1984-82502014000400693. Accessed on January 22, 2018.
  3. The Institute of Cancer Research. “Discovering early chemotherapy drugs.” Retrieved from https://www.icr.ac.uk/about-us/our-achievements/our-scientific-discoveries/we-discovered-chemotherapeutic-agents-which-are-still-in-use-more-than-50-years-later. Accessed on January 22, 2018.

  4. U.S National Library of Medicine. “Safety and Efficacy of TTFields (150 kHz) Concomitant With Pemetrexed and Cisplatin or Carboplatin in Malignant Pleural Mesothelioma (STELLAR).” Retrieved from https://clinicaltrials.gov/ct2/show/NCT02397928. Accessed on January 22, 2018.
  5. 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. Accessed on January 22, 2018.

Last modified: May 7, 2018