One of the biggest challenges in mesothelioma treatment has been the search for effective chemotherapy. The rarity of the disease makes it especially hard to research and treat, and many cases of mesothelioma have not responded to standard chemotherapy.

It has been about 10 years since the first effective chemotherapy treatment was approved by the Food and Drug Administration for mesothelioma. This was the combination of Alimta and cisplatin. Although the combination has shown to improve survival times in many patients, doctors are still looking for more effective treatments. There is a considerable amount of patients who may not respond to this combination.

Doctors have been searching for alternative methods outside the chemotherapy realm because this disease can be so stubborn.

Why Does Mesothelioma Resist Chemotherapy?

There are many reasons why some cases of mesothelioma don’t respond to chemotherapy. Some tumors even develop a resistance to chemotherapy after a successful first round of treatments. This is often referred to as “acquired resistance.”

In some cases, cancer cells replicate too quickly for some chemotherapy drugs to have a significant impact. Sarcomatoid mesothelioma cell types spread faster than epithelioid types, making them more resistant to chemotherapy. However, epithelioid cell types can evade chemotherapy as well.

The issue at hand is that researchers haven’t been able to pinpoint exactly how chemotherapy kills cancer cells.

“Chemotherapy has cured millions of people, but we don’t know why it works,” said Dr. Anthony Letai in a National Cancer Institute bulletin last year. Once the medical community understands how chemotherapy works, it will be easier to understand how cells resist it.

Some of the hypotheses of why certain cancers are or become resistant to chemotherapy are:

  • Cancerous cells can learn to recognize chemotherapy and mutate into a resistant form.
  • The proteins responsible for carrying chemotherapy to mesothelioma cells may stop working.
  • The DNA in the mesothelioma cells can sometimes repair itself before getting killed off.

Tackling Resistance

The most common way mesothelioma is handled when chemotherapy is ineffective is by using a different drug. This is known as second line chemotherapy.

Some common second line chemotherapy drugs used in mesothelioma patients are:

  • Gemcitabine – Often used in combination with Alimta for patients with a resistance to cisplatin
  • Navelbine – Sometimes used in combination with gemcitabine when neither Alimta nor cisplatin are a viable option
  • Doxorubicin – Not used as commonly any more because of its side effects, but may be used when other options are exhausted

The reason mesothelioma is usually treated with a combination of chemotherapy drugs also has to do with fighting resistance.

It is extremely important to choose the most effective chemotherapy option for the patient during first line therapy. Mesothelioma can develop a resistance during the first rounds of chemotherapy. In this case, drugs similar to those used in the first rounds may no longer work either. For example, if the patient becomes resistant to cisplatin, they are likely to resist other platinum-based drugs, such as carboplatin.

Novel Treatments May Make Chemotherapy More Effective

Clinical trials are usually a good path for chemotherapy-resistant mesothelioma patients. In fact, many clinical trials are launched with the specific purpose of treating these types of patients.

Mary Hesdorffer of the Meso Foundation recently stated in an annual meeting of the board that patients now have more options than ever through clinical trials. Clinical trials are often seen as a solution when a patient resists chemotherapy.

Hesdorffer was quoted for resonating the optimism surrounding clinical trials in the mesothelioma research community.

“A clinical trial is a unique opportunity for a patient to try something new and innovative that could have a very positive impact on the patient’s disease.”

Importantly, there are also many clinical trials for late stage mesothelioma patients who have historically been considered untreatable. The innovations and progress made by researchers is slowly changing that.

There are drugs being tested in clinical trials that have demonstrated potential to weaken mesothelioma cells in order to make chemotherapy more effective.

Many of the clinical trials for late stage patients involve novel treatments that move away from the traditional chemotherapy paradigm. Drugs that target the immune system and DNA responsible for tumor blood vessel growth are becoming more common as well. These types of drugs take a different approach to fighting mesothelioma opposed to how chemotherapy is believed to work.

The clinical trial involving a drug known as defactinib, for example, was recently reported to be progressing well in stabilizing the patients’ disease. Defactinib works by targeting mesothelioma stem cells. “We continue to see encouraging clinical signals,” reported the chief medical officer of Verastem, the pharmaceutical company that developed the drug.

Patients should always take clinical trials into consideration, especially since there are currently various emerging treatments with serious potential available. If you are interested in expanding your treatment options, learn more about getting connected to these trials.

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    About the Writer, Andrew Devine

    Andrew Devine is a contributing writer for Mesothelioma Guide. He has developed an interest in educating patients and their families on everything from new treatments to what to expect after diagnosis.