OPINION POST

I’m continually seeing certain drugs for the treatment of Neuroendocrine Tumours (NETs) described as “chemotherapy”. I think there must be some confusion with more modern drugs which are more targeted and work in a different way to Chemotherapy.  According to Mayo Clinic: “In many ways, cytotoxic chemotherapy is “targeted” at specific molecules that regulate progression through the cell cycle; however, these targets are generally not specific for tumor cells. Because systemic cytotoxic chemotherapy targets all rapidly dividing cells, it also attacks hair follicles, gastrointestinal mucosa, and hematopoietic cells thereby inducing the classical side effects of treatment such as alopecia, nausea, diarrhea, mucositis, and bone marrow suppression. The newer generation of targeted biological therapies is still administered systemically as traditional chemotherapy; however, these drugs are unique in that they are designed to target specific molecular components in tumor cell biology with the hope of minimizing cytotoxicity to noncancerous cells. In addition, they have toxicities specific to their mechanism of action”. 

I researched several sites, and they all tend to provide a summary of chemotherapy which is worded like this:  Chemotherapy means:

a treatment of cancer by using anti-cancer medicines called cytotoxic drugs.  Cytotoxic medicines are poisonous (toxic) to cancer cells. They kill cancer cells or stop them from multiplying. Different cytotoxic medicines do this in separate ways. However, they all tend to work by interfering with some aspect of how the cells divide and multiply. Two or more cytotoxic medicines are often used in a course of chemotherapy, each with a separate way of working. This may give a better chance of success than using only one. There are many different cytotoxic medicines used in the treatment of cancer. In each case the one (or ones) chosen will depend on the type and stage of your cancer. Interestingly, there are several statements along the lines of ‘Cytotoxic medicines work best in cancers where the cancer cells are rapidly dividing and multiplying’, a key issue with lower grade NETs.

The old-fashioned view?  

In the past, any medication used to treat cancer was regarded as chemotherapy. However, over the last 20 years, new types of medication that work in a different way to chemotherapy have been introduced. Many of these new types of medication are known as targeted therapies. This is because they’re designed to target and disrupt one or more of the biological processes that cancerous cells use to grow and reproduce.  They are often classed as biological therapy (or biotherapy for short).  In contrast, chemotherapy medications are mostly systemic in nature and designed to have a poisonous effect on cancerous cells, thus the term ‘cytotoxic’.

I suspect the confusion comes from healthcare professionals and pharma companies, not patients.  Some cite the term “antineoplastic” which is something from their medical training.  In short, it means anything to treat cancer. Back in the day, the term was expanded to “antineoplastic chemotherapy” and its use has been overtaken by an avalanche of different types of therapy including but not limited to targeted therapy, biological therapy, immunotherapy and radioligand therapy.  The problem is that some healthcare professionals and pharma’s continue to use the term “antineoplastic chemotherapy“.  That then causes great confusion in patients with cancer types such as Neuroendocrine Cancer who have a worrying connotation of the term “chemotherapy”.  

But when you look at progressive websites such as Mayo Clinic, you then start to see how these terms should be interpreted in the 21st century.  “Antineoplastic therapies can be classified as either cytotoxic systemic chemotherapy or targeted biological therapy“.  Note the use of the term “Antineoplastic Therapy” and “Antineoplastic Agents“. However, there are much wider definitions that include every single type of anti-cancer therapy including hormonal agents etc – I liked this source.  

Context from Neuroendocrine Cancer sources

I have yet to find a document from a Neuroendocrine Cancer scientific organisation, a document from a NET Specialist, or watch a presentation from any NET Specialist, where it will list all the treatments for Neuroendocrine Cancer with drugs such as somatostatin analogues, targeted therapies such as Everolimus (Afinitor) and Sunitinib (Sutent) under the heading of “Chemotherapy”.  Describing them in this way would not only be confusing but may cause alarm to the recipient patients. 

Most sources describe them as follows:

Somatostatin Analogues e.g. Sandostatin (Octreotide), Somatuline (Lanreotide).  Although these drugs have an anti-cancer effect for some, they are also hormone inhibitors and are therefore also hormone therapy.

Everolimus (Afinitor).  This is a targeted biological therapy or more accurate a mammalian target of rapamycin (mTOR) inhibitor. It is a type of treatment called a signal transduction inhibitor. Signal transduction inhibitors stop some of the signals within cells that make them grow and divide. Everolimus stops a particular protein called mTOR from working properly. mTOR controls other proteins that trigger cancer cells to grow. So everolimus helps to stop the cancer growing or may slow it down.

Sunitinib (Sutent).  This is a targeted biological therapy or more accurate a protein (or tyrosine) kinase inhibitor. Protein kinase is a type of chemical messenger (an enzyme) that plays a part in the growth of cancer cells. Sunitinib blocks the protein kinase to stop the cancer growing. It can stop the growth of a tumour or shrink it down.

Chemotherapy for Neuroendocrine Cancer

Like many cancers, chemotherapy is used in Neuroendocrine Cancer, particularly in poorly differentiated types but also in certain types and grades of well-differentiated tumours (despite what you read in patient forums).  Read more about Chemotherapy for Neuroendocrine Cancer – click here. 

Well-known chemotherapy treatments for Neuroendocrine Cancer include (but are not limited to): Capecitabine (Xeloda), Temozolomide (Temodal), Fluorouracil (5-FU), Oxaliplatin (Eloxatin) Cisplatin, Etoposide (Etopophos, Vepesid), Carboplatin, Streptozotocin (Zanosar). Some of these may be given as a combination treatment, e.g. CAPecitabine and TEMozolomide (CAPTEM).

Summary

I can only speculate why some of the confusion exists, but I do have some personal experience I can quote too. Firstly, I believe it could be easier for some healthcare professionals to describe the new agents as ‘chemotherapy’ rather than explain things such as somatostatin analogues, ‘mammalian target of rapamycin (mTOR) inhibitors’, protein kinase inhibitor or angiogenesis inhibitors.

Another reason is that health insurance companies do not have the correct database structures in place on their IT systems and therefore need to ‘pigeonhole’ drugs into the closest category they can see. Often this is the archaic term “antineoplastic chemotherapy”, and this only adds to the confusion. In the days when I had health insurance, my Lanreotide injections were coded as chemotherapy on all my bills. I challenged it and this is exactly how they explained the issue. I suggested they feedback my concern to their data management team. 

But as I said above, I have yet to find a NET specialist who calls these drugs “chemotherapy”

I’m sure there are other reasons why people insist on calling it chemo.