Platinol (cisplatin) is a platinum-based chemotherapy drug often used to treat pleural mesothelioma. The U.S. Food and Drug Administration (FDA) approved it in 1978. Cisplatin is often used in combination with other drugs and can cause serious side effects that must be carefully monitored.
What Is Cisplatin?
Cisplatin is a platinum-containing chemotherapy drug that specifically attacks fast-growing cells in the body. It is administered intravenously over several hours but often only once every three to four weeks.
For mesothelioma, cisplatin is usually combined with pemetrexed, gemcitabine, or immunotherapy drugs.
What Does Cisplatin Do in the Body?
Cisplatin causes cancer cells to die by binding to and distorting DNA, triggering cell death.[1] This drug also affects healthy cells and can lead to certain side effects. Patients are typically given as much of the drug as they can handle.
Which Cancers Does Cisplatin Treat?
FDA approval for cisplatin includes the treatment of advanced testicular, ovarian, and bladder cancers.[1]
Off-label uses for cisplatin include[2]
- Cancers of the head and neck
- Breast cancer
- Cervical cancer
- Lung cancer
- Mesothelioma
When first introduced in 1978, many considered cisplatin to be a cure for testicular cancer. Although its discovery was accidental, the drug has saved countless lives and continues to be an important part of cancer research and clinical trials.[3]
How Is Cisplatin Used in Mesothelioma Treatment?
In many cases, cisplatin is an off-label treatment for mesothelioma. It is a potent chemotherapeutic that helps some patients live longer. Cisplatin can be used in several ways to treat mesothelioma patients.
Oncologists may use it after surgery to clean up the cancer cells the surgeon could not physically remove.
For patients who are poor candidates for surgery, cisplatin and other drugs can help slow the progression of the disease.
Cisplatin with Gemcitabine
The only FDA-approved mesothelioma treatment with cisplatin is in combination with gemcitabine. Gemcitabine is a drug called an antimetabolite.
An Australian clinical trial found that about half of patients responded well to the combination. For these patients, survival time was extended by an average of ten months.[4]
A combination of radical surgery, radiation, and chemotherapy with cisplatin, doxorubicin, and cyclophosphamide significantly improved survival times for patients.[4]
Cisplatin with Doxorubicin
Combined with doxorubicin, cisplatin is often used for patients in advanced stages of mesothelioma. This drug combination, used mainly for palliative care, assists in relieving cancer symptoms and helping patients feel more comfortable.
Doxorubicin may also be combined with cisplatin for HIPEC, hyperthermia intraperitoneal chemotherapy. HIPEC treats peritoneal mesothelioma patients by circulating a bath of heated chemotherapy drugs through the abdominal cavity.[5]
A newer type of therapy, HITHOC, uses a similar strategy to treat pleural mesothelioma. Circulating a combination of cisplatin and doxorubicin through the chest cavity is still under investigation but is promising.
A study of HITHOC reported the treatment results on 71 patients in 2019. Each patient underwent pleurectomy/decortication surgery followed by HITHOC. For patients who could undergo complete resection of the tumors, the median survival time was an impressive 28.1 months.[6]
Cisplatin with Pemetrexed
Cisplatin has also been combined with Alimta (pemetrexed) for mesothelioma patients. Pemetrexed is an approved chemotherapy drug for mesothelioma.
Clinical trials show that patients with mesothelioma live longer when given this combination than when receiving cisplatin alone, and the FDA approved it as a therapy for pleural mesothelioma in 2004.[7]
Enhancing Sensitivity to Cisplatin
Cisplatin is a part of standard mesothelioma treatment, but its effectiveness is limited. Researchers recently reported on the combination of cisplatin with a drug called entinostat for mesothelioma treatment.
They found that the addition of this other drug enhanced the effectiveness of cisplatin by improving platinum uptake in the cancer cells.[8]
Cisplatin Resistance in Mesothelioma Patients
Combining cisplatin with other medications has been a basic treatment approach for decades for a very important reason. While cisplatin is often initially successful at stopping tumor growth, many patients have recurrences because they develop resistance to it.
Using cisplatin along with other chemotherapy drugs may decrease the risk that a patient will become resistant. Researchers also continue to develop other platinum-based chemotherapy drugs to overcome the issue of resistance.
What Are the Common Side Effects of Cisplatin?
Because cisplatin kills rapidly growing cells indiscriminately, it can cause several common side effects. Most of these side effects subside once chemotherapy treatment is complete:[2]
- Nausea
- Vomiting
- Hair loss
- Diarrhea
- Changes in taste
- Low red and white blood cell counts
- Hearing loss
- Numbness and tingling in the fingers and toes
Patients can manage these side effects to some extent. For example, doctors may recommend a course of vitamin B12 supplements to avoid anemia and fatigue.
All patients are also given anti-nausea medications while on a course of cisplatin. Alternative therapies like acupuncture and massage may also help patients cope with side effects.
Serious Side Effects and Toxicity of Cisplatin
Cisplatin can also cause serious side effects. Patients should report any of these signs to a doctor immediately.
Cisplatin carries a black box warning, which is the FDA’s most severe warning label. A black box warning ensures patients and doctors understand the potential for serious risks while using this medication.[2]
Kidney Toxicity
One serious concern is kidney toxicity. The platinum in cisplatin can cause kidney damage in some patients, especially those with previous kidney problems. To reduce this risk, cisplatin is often administered with extra bags of IV hydration to ensure that patients frequently urinate during and immediately after a dose.
Patients are also instructed to drink plenty of water after their dose. Patients on cisplatin who experience severe fatigue, decreased urination, or swelling in the legs, arms, feet, hands, or face should immediately report these concerns to their doctor.[2]
Hearing Loss
Hearing loss is another possible serious issue. Cisplatin can cause permanent hearing loss, especially in children. Patients who experience ringing in the ears or reduced hearing volume should inform their provider with details of their concerns.[2]
Other Serious Side Effects
Patients on cisplatin should also watch for signs of infection, including chills, fever, bloody stool, bloody vomit, seizures, vision loss, eye pain, muscle cramps, and chest pains.
Some people may have a severe reaction to cisplatin, including rash or irritation at the injection site, swelling in the face and mouth, difficulty breathing, hives, and dizziness.[2]
Alternatives to Cisplatin
For some patients, the side effects of cisplatin can be severe. These patients may benefit from alternative platinum chemotherapy like carboplatin or another medication that does not contain platinum.
Who Should Not Use Cisplatin?
All patients, along with their doctors, must weigh the potential benefits with the risks and side effects of cisplatin. If you have mesothelioma, your doctors will determine if you are a good candidate for chemotherapy with cisplatin.
According to the FDA, although it can cause serious side effects, cisplatin’s only contraindication is for people who are hypersensitive to it.[1]
The Latest Cisplatin and Mesothelioma Research
Cisplatin has been used for decades, but researchers continue to use it in studies as a treatment for mesothelioma.
Researchers published the results of a phase II clinical trial adding the immunotherapy drug bevacizumab to the standard combination of pemetrexed and cisplatin in 2015. They reported a significant extension of overall survival with this combination compared to the standard treatment alone.[9]
Researchers are also working on new ways to overcome cisplatin resistance. A recent study found that a particular type of substance called metallothionein may be responsible for the phenomenon. Blocking the expression of metallothionein might help reduce a patient’s resistance to cisplatin.[10]
Cisplatin Clinical Trials Recruiting Mesothelioma Patients
The National Institutes of Health currently lists 18 clinical trials using cisplatin and recruiting mesothelioma patients. These are a few examples:
- A Pilot Window-Of-Opportunity Study of the Anti-PD-1 Antibody Pembrolizumab in Patients With Resectable Malignant Pleural Mesothelioma. This is another study recruiting pleural mesothelioma patients to combine an immunotherapy drug with cisplatin and pemetrexed chemotherapy.[11]
- Treatment of Malignant Peritoneal Mesothelioma (MESOTIP) (MESOTIP). This study is an opportunity for peritoneal mesothelioma patients to access experimental treatments. The trial is comparing standard intravenous cisplatin/pemetrexed chemotherapy with a new chemotherapy delivery method. The new method uses pressurized aerosols to deliver chemotherapy drugs to the abdominal cavity.[12]
- A Study of Additional Chemotherapy After Surgery for People With Malignant Peritoneal Mesothelioma. In this study, researchers are comparing intravenous and intraperitoneal chemotherapy outcomes using pemetrexed with cisplatin or carboplatin.[13]
For many patients with mesothelioma, cisplatin plays a key role in the effective treatment and management of the disease. While the potential side effects can be uncomfortable or even severe, most patients tolerate the drug well. With continued research into cisplatin combinations with other drugs, even more patients could benefit from its positive effects.
