The Role of Chemotherapy in Mesothelioma Treatment

For decades, chemotherapy has been the most widely used systemic treatment for mesothelioma. While it is not a cure, chemotherapy has helped slow tumor growth, relieve symptoms, and extend survival in some patients. However, mesothelioma remains one of the most chemotherapy-resistant cancers, making treatment a complex challenge.

In this guide, we will break down chemotherapy’s role in mesothelioma treatment, covering drug effectiveness, combination regimens, experimental treatments, and future prospects.

How Chemotherapy Works

Chemotherapy uses powerful drugs to kill or slow the growth of cancer cells. These drugs work by interfering with the cell cycle, stopping cancer cells from dividing and spreading.

For mesothelioma, chemotherapy is used in three key ways:

1. Primary Treatment (First-Line Therapy): Used when surgery isn’t an option.
2. Adjuvant Therapy (After Surgery): Used to kill remaining cancer cells.
3. Neoadjuvant Therapy (Before Surgery): Used to shrink tumors before surgery.

Chemotherapy is usually delivered intravenously (through a vein), but in some cases, it is administered directly into the pleural or peritoneal cavity (intracavitary chemotherapy) for more targeted effects.

The Challenges of Chemotherapy for Mesothelioma

Why is Mesothelioma Resistant to Chemotherapy?

Unlike other cancers, mesothelioma does not form a single tumor mass—instead, it spreads across the lining of the lungs, abdomen, or heart, making it harder for chemotherapy to reach all cancerous cells.

Additionally, mesothelioma cells often:

• Overexpress drug resistance proteins, making them less responsive to chemotherapy.
• Have a slow cell division rate, meaning fewer cells are in a vulnerable state for chemotherapy to target.

Despite these challenges, researchers have identified drug combinations that offer some effectiveness, and new treatment approaches are being tested in clinical trials.

Single-Agent Chemotherapy: Limited Success

Over the years, many single chemotherapy drugs have been tested, but none have been highly effective alone. The average response rate is 10-15%, meaning only a small percentage of patients experience tumor shrinkage.

Most Studied Single-Agent Drugs

While none of these drugs alone are highly effective, combining them has shown better results.

Combination Chemotherapy: A Step Forward

Because single-agent chemotherapy has limited success, oncologists typically use drug combinations to increase effectiveness.

Best Performing Drug Combinations

Why Does Combination Therapy Work Better?

• Targets cancer cells in multiple ways, increasing the likelihood of response.
• Reduces the chance of drug resistance, as mesothelioma cells have a harder time adapting to multiple drugs.
• Some combinations boost chemotherapy uptake, increasing its effectiveness.

Cisplatin + Pemetrexed: The Gold Standard

The most effective chemotherapy combination for mesothelioma is Cisplatin + Pemetrexed (Alimta).

• FDA-approved in 2004
• Improves survival by several months compared to single-agent therapy
• Can be combined with vitamin B12 and folic acid to reduce side effects

For patients who cannot tolerate cisplatin, carboplatin + pemetrexed is an alternative with similar effectiveness but fewer side effects.

Targeted & Intracavitary Chemotherapy

Intrapleural and Intraperitoneal Chemotherapy

Instead of delivering chemotherapy through the bloodstream, some patients receive it directly into the affected cavity (pleural or peritoneal space).

• Intrapleural chemotherapy: Used for pleural mesothelioma to attack tumors directly.
• Hyperthermic Intraperitoneal Chemotherapy (HIPEC): Heated chemotherapy applied during surgery for peritoneal mesothelioma.

Newer Approaches: Targeted and Immunotherapy

• Targeted Therapy: Uses drugs that block specific molecules cancer cells need to grow.
• Immunotherapy + Chemotherapy: Drugs like nivolumab and pembrolizumab are being tested alongside chemotherapy.

Side Effects of Chemotherapy

Chemotherapy can cause a range of side effects, depending on the drug used.

Common Side Effects

• Nausea and vomiting
• Fatigue
• Hair loss
• Lowered immune function (increased infection risk)
• Kidney and nerve damage (cisplatin-specific side effect)

Doctors often prescribe medications and supportive care to help manage side effects.

Clinical Trials and Future Chemotherapy Research

Since mesothelioma is rare, large-scale chemotherapy trials have been difficult to conduct. However, ongoing clinical trials are exploring new drugs and combinations.

Experimental Chemotherapy Combinations

Many new chemotherapy approaches focus on personalized treatment, ensuring patients receive the best combination based on their tumor genetics.

Final Thoughts

• Chemotherapy is not a cure for mesothelioma, but it remains the most effective systemic treatment.
• Combination chemotherapy works better than single drugs, with Cisplatin + Pemetrexed as the gold standard.
• Newer techniques like intrapleural and intraperitoneal chemotherapy offer more targeted effects.
• Ongoing research and clinical trials are testing new drug combinations, including immunotherapy.
• Personalized treatment approaches may improve outcomes in the future.

If you or a loved one is considering chemotherapy for mesothelioma, it’s essential to discuss all available options with a specialist and consider clinical trials for cutting-edge treatments.