Mesothelioma Treatment: Chemotherapy for Mesothelioma

Within the standard framework of cancer treatments, chemotherapy is considered the most effective single modality for the treatment of mesothelioma and is likely to be the most commonly deployed treatment as well. Most people who are diagnosed with the disease in its later stages are not eligible for “curative” surgeries, so chemotherapy becomes their best chance at extending life. For patients who are diagnosed in an earlier stage or are otherwise candidates for surgery, chemotherapy is likely to be used along with surgery and radiation therapy in a multimodal treatment protocol.

Even though chemotherapy can be effective at extending life, it is not a curative treatment for the disease because mesothelioma is not presently curable. Even as advancements in our treatments have led to longer survival times and better control of patient symptoms, the disease continues to resist long-term management and survival.

Mesothelioma Treatment: Chemotherapy — Pemetrexed + Cisplatin
(Alimta Therapy)

The current chemotherapy standard of care for the treatment of pleural mesothelioma is combination therapy utilizing pemetrexed and cisplatin. Pemetrexed is manufactured by Eli Lilly and is marketed under the trade name Alimta®, so this treatment regimen is also known asAlimta therapy. The introduction of pemetrexed was a watershed event in mesothelioma treatment, as it was the first treatment to show quantifiable increases in median survival time and symptom control when compared to traditional therapies. Due to these successes, the FDA approved pemetrexed in combination with cisplatin in 2004. This was a significant moment because pemetrexed was the first chemotherapy treatment the FDA had ever approved for mesothelioma and it remains the only one.

Since its initial approval and introduction, subsequent studies have confirmed pemetrexed’s clinical benefits. These studies have demonstrated similar increases in median survival time and time-to-progression, as well as comparable increases in quality-of-life and symptom control. Due to the success of these confirmatory studies, most national health care systems have since approved pemetrexed + cisplatin as first-line chemotherapy treatment for pleural mesothelioma.

There is not yet a standard chemotherapy regimen for the treatment of peritoneal mesothelioma, or for the other forms of the disease. In many cases, pemetrexed + cisplatin will still be the therapy of choice for these rare forms of mesothelioma, but their diagnostic infrequency when compared with pleural mesothelioma means that clinical studies are few and far between, so there are not many opportunities to compare therapeutic effectiveness between different treatment regimens.

About Pemetrexed/Alimta

Pemetrexed is a type of chemotherapy drug known as an antifolate, which is a class of drugs that inhibit the activity that folic acid plays in the cell cycle. Pemetrexed interferes with the production of specific enzymes that are necessary for the production of DNA and RNA, which are necessary for the development of all cells. Thus, pemetrexed’s anticancer activity derives from its ability to disrupt essential aspects of cell division and replication. Pemetrexed’s efficacy for mesothelioma treatment is based on its ability to slow the growth of malignant mesothelioma cells—an ability which is presently unsurpassed among other chemotherapy agents.

To learn more about antifolates, please read the following: Mesothelioma Treatment: Chemotherapy Agents and Drug Classes.

About Cisplatin

Cisplatin was the first member of the class of chemotherapy drugs known as platinum agents and is currently used in chemotherapy regimens for a variety of cancers, including mesothelioma. Cisplatin disrupts cell replication by creating unstable cross-links in a cell’s DNA structure, which prevents the cell from replicating. Like pemetrexed, when cisplatin was approved in 1978, it was considered a watershed moment in the efficacy of chemotherapy treatments.

Cisplatin is one of the most important chemotherapy agents used in the treatment of pleural mesothelioma. It was first studied for this purpose in single-agent therapy, but it demonstrated limited effectiveness and carried a high likelihood of severe treatment-related side effects. Subsequent research revealed that cisplatin is most effective when used in combination therapy. It has been studied with gemcitabine, which is a chemotherapy drug that has been used to treat pleural mesothelioma and various forms of lung cancer, as well as in combination with other agents, such as mitomycin and vinblastine. Overall response rates for these treatments were generally disappointing and none of them matched the activity generated by cisplatin and permetrexed.

To learn more about platinum agents, please read the following: Mesothelioma Treatment: Chemotherapy Agents and Drug Classes .

Treatment Regimen

A patient normally undergoes pemetrexed + cisplatin chemotherapy on an outpatient basis. The standard treatment plan defines a 21-daychemotherapy cycle. On the first day of each cycle, the patient is given the drug combination. Pemetrexed is given first and then cisplatin is delivered. No further therapy is delivered for the next 20 days, which gives the body’s normal cells time to recover. Then the regimen starts anew. Thus, another round of administrations is given every 22nd day. A patient’s doctor will decide how many cycles will be necessary at the start of treatment, but tests during each of the cycles may lead to adjustments.

Alternative Chemotherapy Regimens

Pemetrexed and cisplatin is the chemotherapy standard of care in the treatment of pleural mesothelioma and is the regimen that will prescribed for most cases of the disease. However, there is an active research community that is investigating alternative agents and treatment regimens, some of which are demonstrating very promising results in pre-clinical studies or early phase trials. For example, clinical studies of a newer chemotherapy drug called vinorelbine have identified it as being among the most active agents for mesothelioma treatment. Much more research needs to be completed on it, but some of these studies have indicated that vinorelbine may generate a treatment response that is similar to pemetrexed. These studies have also demonstrated its potential for higher side effects, but in most cases, the researchers called for more research into its potential for mesothelioma treatment.

Pemetrexed + cisplatin will likely remain the chemotherapy standard of care for the foreseeable future, but studies on vinorelbine and other alternative agents are indicative of the mesothelioma research community’s dedication to finding a cure for this difficult disease.

Related Information: Chemotherapy & Mesothelioma

For more information related to chemotherapy and mesothelioma treatment, please read the following:

• Mesothelioma Treatment: What is Chemotherapy?
• Mesothelioma Treatment: Chemotherapy Agents and Drug Classes