Cisplatin is a platinum-based chemotherapy drug. Cisplatin in combination with the chemotherapy drug pemetrexed is approved to treat pleural mesothelioma. Cisplatin is also used in several innovative mesothelioma treatment techniques. Multimodal treatment approaches involving HIPEC, immunotherapy and TTFields may use cisplatin.

01. What Is Cisplatin?

What Is Cisplatin?

Cisplatin is a chemotherapy drug approved to treat pleural mesothelioma. It is also known by its former brand name, Platinol®-AQ, which has been discontinued. Cisplatin is a small, platinum-containing molecule. It can interfere with cell growth and division and cause cells to kill themselves. This can help halt tumor growth.

In 2004, the U.S. Food and Drug Administration (FDA) approved a combination of cisplatin and pemetrexed to treat pleural mesothelioma. Pemetrexed is often referred to by its brand name, Alimta®. The FDA first approved cisplatin in 1978 for testicular and bladder cancer treatment. Cisplatin chemotherapy treatment is also approved for ovarian cancer.

Cisplatin is often used with other mesothelioma drugs to deliver more effective treatment. The combination of cisplatin and pemetrexed is the only FDA-approved chemotherapy for mesothelioma. However, researchers have studied the effects of combining cisplatin with other drugs. Some studies indicate beneficial results. When treating mesothelioma patients, doctors may also use cisplatin with other chemotherapy drugs such as:

  • Bevacizumab
  • Doxorubicin
  • Gemcitabine

Cisplatin can also be combined with other types of treatment. For example, cisplatin and pemetrexed treatment results may improve in combination with immunotherapy. At least one study suggested improved clinical benefits from this combination. The results showed improved overall survival for malignant pleural mesothelioma (MPM) patients.

Cisplatin Quick Facts

  • Generic names: Cisplatin, CDDP
  • Brand names: Platinol (discontinued), Platinol-AQ (discontinued)
  • Administration: Intravenous
  • Often combined with: Cisplatin is often combined with pemetrexed (Alimta). Both chemotherapies work to interfere with cell growth.
  • Types of mesothelioma treated: Biphasic mesothelioma, epithelioid mesothelioma, peritoneal mesothelioma, pleural mesothelioma, sarcomatoid mesothelioma
  • Manufacturer: Accord Healthcare, Athenex Pharmaceutical Division, LLC, BluePoint Laboratories, Fresenius Kabi USA, LLC, Gland Pharma Limited, Teva Parenteral Medicines, Inc., West-Ward Pharmaceuticals Corporation, WG Critical Care, LLC
  • FDA approval: Cisplatin plus pemetrexed is approved for first-line treatment of pleural mesothelioma. Patients ineligible for resection may be candidates for this type of chemotherapy. Cisplatin with pemetrexed is also approved for first-line treatment of non-small cell lung cancer. Cisplatin is approved on its own for second-line treatment of non-small cell lung cancer.
02. Cisplatin and Mesothelioma

How Does Cisplatin Treat Mesothelioma?

Patients may receive a combination of cisplatin and pemetrexed for malignant mesothelioma treatment. Cisplatin and pemetrexed are both chemotherapy drugs. Cisplatin is made of a platinum compound. It can bind DNA and thereby slow the growth of or kill cancer cells.

Cisplatin chemotherapy causes cells to kill themselves through apoptosis. Cells use apoptosis as a kind of guardrail protecting against cancer-like behaviors. If apoptosis does not work properly, cells can grow uncontrollably and cause tumors.

Standard first-line treatment for pleural mesothelioma consists of cisplatin and pemetrexed. Doctors commonly use this combination for second-line treatment for pleural mesothelioma as well.

Cisplatin also plays a part in more innovative methods of administering chemotherapy. Doctors commonly use cisplatin in heated intraperitoneal chemotherapy (HIPEC) procedures. HIPEC is a heated chemotherapy wash administered to the abdominal cavity after surgery. It may improve survival for peritoneal mesothelioma patients. Cisplatin also has a role in hyperthermic intrathoracic chemotherapy (HITHOC) procedures. HITHOC is similar to HIPEC and may improve survival for pleural mesothelioma patients.

Cisplatin and Pemetrexed for Pleural Mesothelioma

In 2004, the FDA approved a combination of cisplatin and pemetrexed to treat unresectable pleural mesothelioma. Both chemotherapy drugs use chemicals to kill cancer cells and prevent them from multiplying.

Resection is the process of cutting out tissue or parts of an organ. If something is unresectable it is not capable of being surgically removed. Doctors may also refer to unresectable tumors as inoperable.

It is not uncommon for mesothelioma treatment to involve a combination of drugs. Some drugs work well together because they kill cancer cells in different ways. Cisplatin and pemetrexed use different mechanisms to kill fast-growing cells.

The FDA approved this regimen of cisplatin and pemetrexed for first-line pleural mesothelioma treatment. Research indicates this combination produces a better response than cisplatin alone. First-line treatment is any treatment combination used in the initial phase of a patient’s treatment regimen. Second-line treatment occurs after this initial phase.

One study found that patients receiving first-line cisplatin chemotherapy alone had a median survival of 9.3 months. Those receiving cisplatin and pemetrexed had a median overall survival of 12.1 months. Adding pemetrexed to cisplatin improved survival by about 30% in this study.

Another study looked at the results of cisplatin and pemetrexed on second-line treatment. The study found different survival results for different pleural mesothelioma treatment regimens:

  • Patients receiving cisplatin plus pemetrexed: 15.3 months median survival
  • Patients receiving only cisplatin: 12.2 months median survival

Currently, cisplatin plus pemetrexed is the only FDA-approved chemotherapy for pleural mesothelioma. But doctors commonly use cisplatin in combination with other drugs to treat different types of mesothelioma.

Cisplatin in HIPEC Procedures for Peritoneal Mesothelioma

Oncologists may use cisplatin by itself or in combination with other chemotherapy drugs in specific procedures. For example, HIPEC procedures commonly use cisplatin to treat peritoneal mesothelioma. In one study, peritoneal mesothelioma patients received HIPEC with cisplatin, with additional treatments. These patients had a median survival of 52 months.

HIPEC stands for heated intraperitoneal chemotherapy. It is a form of heated chemotherapy that doctors administer in the abdomen. HIPEC may cause fewer side effects than traditional chemotherapy because it is concentrated in the abdomen. Traditional chemotherapy is administered through a vein and circulates throughout the bloodstream.

Other HIPEC procedures may use a combination of cisplatin and another chemotherapy drug. For example, cisplatin may be combined with doxorubicin. One study consisted of a group in which 80% of patients underwent HIPEC with cisplatin and doxorubicin. The researchers found a median overall survival of 53 months for all study patients.

Cisplatin and mitomycin may also be used in HIPEC procedures for peritoneal mesothelioma. In one study, patients received this form of HIPEC as part of a multi-step treatment. Patients treated with cisplatin and mitomycin HIPEC procedures had a median survival of 54.9 months.

Cisplatin in HITHOC Procedures for Pleural Mesothelioma

Cisplatin may also be used in HITHOC procedures, which are similar to HIPEC. HITHOC procedures also use heated chemotherapy. However, HITHOC places heated chemotherapy drugs in the chest cavity instead of the abdomen. This puts the drugs in a good position to address pleural mesothelioma tumors.

HITHOC stands for hyperthermic intrathoracic chemotherapy. It is a form of heated chemotherapy administered within the chest cavity. This approach keeps the chemotherapy drugs in one place instead of circulating them throughout the bloodstream. HITHOC may not cause some of the side effects associated with traditional, intravenous chemotherapy.

One study treated pleural mesothelioma patients with surgery followed by HITHOC with cisplatin and doxorubicin. Patients whose surgery removed all visible tumors had a median survival of 28.2 months.

03. What to Expect

What to Expect During Treatment

Cisplatin plus pemetrexed treatment infusions for pleural mesothelioma patients occur every three weeks. Patients may receive four to six treatments over the course of three to six months.

Before their first infusion, the patient takes preparatory steps to minimize side effects. In the week leading up to the infusion:

  • The patient must take at least five daily doses of folic acid.
  • The patient must receive one intramuscular injection of vitamin B12.
  • The patient may be treated with a dose of a steroid the day before their first infusion.

The patient will continue to receive folic acid and B12 supplements during and after treatment. They may also receive additional steroid shots on the day of and the day after treatment.

Pleural mesothelioma patients will receive their infusion at a hospital. Their intravenous infusions are given in several stages. Dosages at each stage are calculated using the surface area of the patient’s skin. The dosages are measured in square meters.

  • Stage 1: 500 mg/m2 of pemetrexed infusion over 10 minutes
  • Stage 2: 30 minutes of rest
  • Stage 3: 75 mg/m2 of cisplatin infusion over two hours

Healthcare providers will monitor this procedure to ensure safety. They will keep an eye on blood cell levels, kidney function and liver function.

After their first infusion, the patient will rest for the next three weeks. Then the patient may return for their next round of treatment. If they receive another infusion, they will spend more time resting and recovering afterward.

There is no set number of times this cycle will be repeated. A doctor will tailor their recommendation to an individual’s needs. One study found more than half of pleural mesothelioma patients received at least six cycles of treatment with cisplatin and pemetrexed.

Preparing for Your Appointment

Patients can take steps to prepare for their chemotherapy appointment. Certain steps can help patients reduce stress and stay organized. For their appointment, patients may want to:

  • Arrange for transportation: Patients may feel tired after their treatments. It is a good idea to have a friend, family member or service provide transportation from the hospital.
  • Clear their schedule: Patients should prepare to rest and recover after their appointment. They should also notify their employers they may need time off during treatment and recovery.
  • Dress comfortably: Patients will be sitting for an extended period of time as they receive treatment. Dressing in warm and non-constrictive clothes can help avoid discomfort.
  • Organize their medical information: It is a good idea for patients to prepare to answer any questions about their cancer journey. Keeping this information organized can help avoid stress.
  • Pack a bag: Patients should pack a bag with items that are helpful to have on hand during treatment. These include snacks, water, crafts and reading material.

Before treatment, doctors will talk to their patients about their chemotherapy drugs. Mesothelioma patients can ask their care team any questions about how to prepare for chemotherapy.

Managing Treatment and Follow-Up Care

Pleural mesothelioma patients may go through several cycles of chemotherapy treatment. One study found patients are likely to go through at least six cycles of cisplatin and pemetrexed treatment. It is important for patients treated with cisplatin to take it easy during treatment cycles.

There are several things patients treated with cisplatin can do to manage treatment, including:

  • Avoiding areas where they might contract an infection
  • Getting plenty of rest
  • Staying hydrated
  • Washing hands

Mesothelioma doctors will track patient progress during treatment and provide follow-up care. Patients are likely to have follow-up appointments during treatment with cisplatin. Doctors may draw blood to check blood cell levels. They may also check a patient’s electrolyte levels and the functioning of certain organs, such as the kidney and liver. They will also watch patients for any allergic reactions.

It is important that patients attend scheduled appointments. They should also stay mindful of their treatment experience and discuss it with their doctor. A doctor can help provide any necessary follow-up care and help treat chemotherapy side effects.

04. Benefits of Cisplatin

Cisplatin Benefits

Cisplatin plus pemetrexed can provide beneficial results for people with pleural mesothelioma. This treatment may improve survival for patients ineligible for surgery. It is the only FDA-approved chemotherapy treatment for pleural mesothelioma.

Cisplatin has also been used in innovative chemotherapy methods with positive results. Using cisplatin in HIPEC procedures may improve survival for peritoneal mesothelioma patients. Cisplatin in HITHOC procedures may improve survival for pleural mesothelioma patients.

There are also possible benefits to combining other types of therapy with cisplatin plus pemetrexed. For example, research has looked into:

Certain studies suggest possible benefits to using these treatments with cisplatin and pemetrexed.

05. Side Effects of Cisplatin

Cisplatin Side Effects

Patients receiving cisplatin chemotherapy for malignant mesothelioma may experience side effects. Nausea and vomiting are common. Side effects may depend on a number of factors. For example, side effects may vary based on whether the drug is combined with other therapies.

The FDA-approved combination of cisplatin plus pemetrexed is generally well-tolerated by patients. Patients may experience nausea, vomiting, fatigue and loss of appetite. They may also experience hair loss or thinning due to the pemetrexed. But the risk of hair loss from pemetrexed is low.

Patients should speak to their doctors ahead of their first chemotherapy appointment. A mesothelioma doctor can explain potential side effects. They can also help manage any side effects that occur during treatment.

Potential Side Effects of Cisplatin

  • Anemia
  • Diarrhea
  • Ear toxicity
  • Hearing damage
  • Heart attack
  • Heart damage
  • Liver damage
  • Loss of appetite
  • Low platelet counts
  • Low white blood cell counts
  • Nausea
  • Peripheral neuropathy (weakness, numbness or pain from nerve damage)
  • Renal toxicity (kidney damage)
  • Serious immune reaction
  • Vision damage*
  • Vomiting

*Improvement or resolution of vision damage usually occurs after cisplatin treatment stops.

Managing Side Effects

Mesothelioma patients may be able to manage chemotherapy side effects in several ways. Patients receiving the cisplatin plus pemetrexed regimen will receive vitamin B12 injections. They may also receive steroid injections. These may be used before, during and after treatment to combat side effects.

One common side effect of cisplatin is nausea. Patients may be able to adjust their nutrition before, during and after chemotherapy to help with nausea. A doctor may also prescribe anti-nausea medication. The patient should take any prescribed medication as instructed.

Patients should speak to their doctor if they experience any side effects. They should also consult with their mesothelioma doctor before using any new drug or supplement. A doctor can inform patients whether the drug or supplement is safe to take with cisplatin. Managing side effects can help improve patients’ quality of life during treatment.

06. Cisplatin Eligibility

Who Is Eligible for Cisplatin?

Pleural mesothelioma patients who do not qualify for surgery may be eligible for cisplatin plus pemetrexed. Other factors may affect patients’ eligibility, including:

  • Ability to engage in daily activity, also called performance status
  • Drug allergies
  • Other medications the patient is taking
  • Pre-existing conditions, such as heart disease, kidney disease and liver disease

Mesothelioma patients should talk to their doctor to determine eligibility. A doctor can outline the benefits and risks of cisplatin and answer any questions. They can also inform patients about other mesothelioma treatment options.

07. Cisplatin Studies

Clinical Trials and Studies on Cisplatin for Mesothelioma

Cisplatin is being used in innovative clinical trials and studies to treat mesothelioma. The use of cisplatin has shown promising results when combined with other drugs and treatment processes. Ongoing clinical trials continue to test combinations to create better patient outcomes.

One study added the immunotherapy drug bevacizumab to the FDA-approved cisplatin plus pemetrexed combination. Bevacizumab helps block the blood supply to cancer cells. The study looked at results in pleural mesothelioma patients. Patients who received a combination of all three drugs had a median survival of 18.8 months. The patients who received only cisplatin and pemetrexed had a median survival of 16.1 months.

Another study looked at 104 pleural mesothelioma patients who underwent surgery. The patients either received an extrapleural pneumonectomy (EPP) or pleurectomy/decortication (P/D). Patients then received a combination of heated cisplatin and gemcitabine within the chest cavity. This means the patients underwent cisplatin-based HITHOC after surgery.

The study found encouraging results for epithelioid mesothelioma patients who underwent either form of surgery. Patients who underwent EPP had a median survival of 25.6 months. The median survival with P/D was 41.6 months.

Cisplatin and Other Types of Therapies

Researchers are examining the benefits of combining other therapies with cisplatin plus pemetrexed. Multimodal therapies using cisplatin and pemetrexed include immunotherapy, targeted therapy and TTFields.

Promising data exists for combining immunotherapy with cisplatin and pemetrexed for pleural mesothelioma. For example, researchers have looked into the potential benefits of durvalumab. Durvalumab is an immune checkpoint inhibitor, a type of immunotherapy. One study found a median survival of 20.4 months when using durvalumab with cisplatin and pemetrexed. In the clinical trial for cisplatin and pemetrexed alone, pleural mesothelioma patients had a median survival of 12.1 months. This means adding durvalumab to cisplatin and pemetrexed may have extended survival by about 8 months.

One study combined cisplatin and pemetrexed chemotherapy treatment with TTFields. TTFields are mild electrical fields that help interrupt cell division. Patients with pleural mesothelioma showed improved results.

Another study looked into the effects of combining targeted therapies with cisplatin plus pemetrexed. Targeted therapies are substances that interfere with cancer cell reproduction. They are different from chemotherapy and immunotherapy. This specific study looked at the effects of nintedanib, a kinase inhibitor, when combined with cisplatin and pemetrexed.

This approach provided benefits for pleural mesothelioma patients with the epithelioid cell type. Median survival for chemotherapy-only patients was 15.2 months. For patients who received chemotherapy and nintedanib results improved to 20.6 months.

Improving Cisplatin’s Efficacy

Researchers are looking into ways to improve the efficacy of cisplatin. One study looked into overcoming chemotherapy resistance when administering cisplatin. A specific compound appeared to impede cancer cells from defending themselves against chemotherapy. Researchers believe this compound could improve the long-term efficacy of cisplatin.

Studies like these seek to improve the drug’s cancer-fighting power. Increased efficacy of cisplatin may improve the survival of mesothelioma patients.