The number of people with Malignant Pleural Mesothelioma is anticipated to increase over the next decade in Europe and the developing nations. Chemotherapy is currently the mainstay of treatment for mesothelioma patients and new chemotherapy agents and combinations of drugs are generating improved results for mesothelioma patients although none have yet been successful as a curative treatment.
What is Chemotherapy and how is it delivered?
Chemotherapy treats cancer with drugs that destroy malignant cells and has been used in the management of cancer since the early 1940’s. Standard chemotherapy agents work by impairing cell division or initiating programmed cellular death (apoptosis) e.g. anti-angiogenesis chemotherapy drugs stop new blood vessels from forming thereby preventing tumours from establishing a pathway through which to receive the nutrients and oxygen required for tumour growth and spread.
The drugs used in chemotherapy management, including those for mesothelioma treatments, are not always used for a curative intent and may be used in conjunction with other treatments. e.g. surgery and / or radiotherapy.
Neoadjuvant or Preoperative Chemotherapy
is used with the intent to reduce the size of a tumour prior to surgery.
Adjuvant Chemotherapy or Postoperative Chemotherapy
is used after surgery if there is a risk of cancer recurrence
Palliative Mesothelioma Chemotherapy
is used to treat symptoms of the disease as opposed to providing a cure.
Sometimes chemotherapy drugs are given on their own i.e. as a single agent but more often two or more drugs are given simultaneously in what is called combination chemotherapy.
Chemotherapy drugs are usually administered intraveneously or orally although a novel delivery system for cisplatin by nebuliser is currently undergoing research at Strathclyde University.
The number of chemo treatments given depends upon the specific chemotherapy regime used and a patient’s chemotherapy dosage varies based on their body surface area.
What Chemotherapy Drugs are used in the Management of Mesothelioma
Combination chemotherapy is usual in the treatment of mesothelioma.
Cisplatin, an ‘old’ chemotherapy drug that first underwent clinical trials back in 1971 is still used today but usually in combination with newer drugs such as Pemetrexed, Onconase and / or Veglin.
Cisplatin is a platinum-based drug type that is part of a family of three similar drugs including Carboplatin and Oxaliplatin. Cisplatin works by cross linking DNA in a number of ways, preventing rapidly dividing cells from duplicating their DNA to accommodate further cell division.
Pemetrexed (marketed under the trade name Alimta) is an anticancer drug and has a chemical structure similar to folic acid. It works by stopping the development of DNA and RNA by preventing the synthesis of thymidine and purine that are necessary for cell growth, effectively stopping the cancer from getting bigger and also kills some cancer cells.
In February, 2004, the U.S. Food and Drug Administration (FDA) approved the use of pemetrexed combined with cisplatin to treat pleural mesothelioma.
In 2008 NICE provided guidelines for the use of Pemetrexed for mesothelioma and recommended that Pemetrexed be used as a possible treatment for malignant pleural mesothelioma in people:
- with advanced disease
- whose cancer is not suitable for surgical resection (removal) and
- who have a World Health Organization (WHO) performance status of:
0 (able to carry out all normal activity without restriction) or
1 (restricted in strenuous activity but able to move around and carry out light work).
What side effects are associated with the chemotherapy drugs?
The side effects associated with mesothelioma chemotherapy will depend on the specific drugs used but may include some / all of the following:
- Neurotoxicity damage to the nerves
- Nephrotoxicity - damage to the kidneys
- Ototoxicity – hearing loss
- Mouth sores
- Skin rashes. Itching
- Extreme fatigue
- Lowered blood count
- Electrolyte imbalance
- Numbness in the extremities
If you have mesothelioma and are about to start chemotherapy treatment, your oncologist will guide you through the expected side effects of your chemotherapy regime as part of the consent procedure.
What are the Future Developments in Drug Therapy for Mesothelioma?
In addition to Cisplatin, Gemcitabine, and Alimta, anti-angiogenesis agents such as Bevacizumap and Endostatin are being investigated by researchers. Ranpirnase (Onconase) is also proving promising in mesothelioma management as is Coramsine.
Now a new drug combination for people with inoperable pleural mesothelioma marks the first new medication for mesothelioma approved by The FDA in 16 years. Following a recent clinical trial of more than 600 patients Ipilimumab And Nivolumab have been approved by The FDA in October 2020.