Cisplatin for Mesothelioma

What Is Cisplatin?

Cisplatin is a chemotherapy drug approved to treat pleural mesothelioma. It is a small, platinum-containing molecule. Cisplatin interferes with cell growth and division. This causes cells to die and can slow or stop 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. Yet, researchers have studied the effects of combining cisplatin with other drugs. Some studies show beneficial results. When treating mesothelioma patients, doctors may also use cisplatin with other drugs. These drugs include:

• Adriamycin® (doxorubicin)
• Avastin® (bevacizumab)
• Gemzar® (gemcitabine)
• Keytruda® (pembrolizumab)

Cisplatin can also be combined with other types of treatment. For example, cisplatin and pemetrexed may be more effective when combined with immunotherapy. In one study, this combination improved overall survival for malignant pleural mesothelioma (MPM) patients.

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How Does Cisplatin Treat Mesothelioma?

Cisplatin chemotherapy causes cells to kill themselves. This process is known as apoptosis. It acts as a guardrail, protecting against cancer-like behaviors. If the process does not work properly, cells can copy themselves uncontrollably. This rampant growth can lead to tumors.

Patients may receive a combination of cisplatin and pemetrexed for malignant mesothelioma treatment. Cisplatin and pemetrexed are both chemotherapy drugs.

Cisplatin also plays a part in more innovative chemotherapy methods.

Doctors commonly use it in heated intraperitoneal chemotherapy (HIPEC) to treat peritoneal mesothelioma. Cisplatin also has a role in hyperthermic intrathoracic chemotherapy (HITHOC) procedures.

Cisplatin and Pemetrexed for Pleural Mesothelioma

Cisplatin and pemetrexed are two chemo drugs that patients often receive as part of the same treatment. Doctors use this combination to treat some cases of pleural mesothelioma. Both chemotherapy drugs are chemicals that can kill cancer cells and slow tumor growth.

It is common for mesothelioma treatment to involve a combination of drugs. Some drugs work well together because they eliminate cancer cells in distinct ways. This is true of cisplatin and pemetrexed, which use different mechanisms to kill cancer cells.

Research indicates this combination produces a better response than cisplatin alone. In one study, patients receiving first-line cisplatin on its own had a median survival of 9.3 months. Those receiving cisplatin and pemetrexed had a median 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 survival results differed between 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 with other chemotherapy drugs in specific procedures. For example, HIPEC procedures commonly use cisplatin to treat peritoneal mesothelioma. In one study, peritoneal mesothelioma patients underwent cisplatin-based HIPEC. They also had other treatments. These patients had a median survival of 52 months.

Other HIPEC procedures may use a combination of cisplatin and another chemo 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 chemo drugs in the chest cavity instead of the abdomen. This puts the drugs in a good position to address pleural mesothelioma tumors.

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.

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What to Expect During Treatment

A doctor can help set expectations about cisplatin chemotherapy. Treatment timing follows a set schedule. Pleural mesothelioma patients commonly have infusions of cisplatin plus pemetrexed every 3 weeks. This often continues for 4 – 6 treatments over 3 – 6 months.

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

• Takes at least 5 daily doses of folic acid
• Receives 1 intramuscular injection of vitamin B12
• Gets 1 dose of a steroid the day before their first infusion

The patient continues 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 generally receive chemo at hospitals or infusion centers. Cisplatin and pemetrexed treatments happen on the same day in stages:

• Stage 1: Pemetrexed infusion lasting about 10 minutes
• Stage 2: 30 minutes of rest
• Stage 3: Cisplatin infusion lasting about 2 hours

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

After the first infusion, the patient rests for the next 3 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 can tailor their recommendation to an individual’s needs. One study found more than half of pleural mesothelioma patients received at least 6 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 6 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 can do when undergoing cisplatin treatment, including:

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

Mesothelioma doctors track patient progress during treatment and provide follow-up care. Patients are likely to have follow-up appointments after their infusions.

Doctors may draw blood to check blood cell and electrolyte levels at follow-up appointments. These tests allow the doctor to watch the function of certain organs, such as the kidney and liver. Doctors also watch patients for 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 provide necessary follow-up care and help with chemotherapy side effects.

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. As part of heated chemo treatments like HIPEC and HITHOC, it has improved survival for many mesothelioma patients.

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

• Immunotherapy
• Tumor Treating Fields (TTFields)

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

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Cisplatin Side Effects

Patients receiving cisplatin chemotherapy for malignant mesothelioma may experience side effects. Nausea and vomiting are common. Side effects may depend on several 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.

Managing Side Effects

Mesothelioma patients may experience side effects during cisplatin treatment. Doctors can help manage these 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.

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.

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.