One of the great things about learning is that it never ends 🙂 I came across this piece of information about how chemotherapy was invented. I had no idea. It began as a deadly cloud but it eventually ended up as a silver lining for certain cancer patients. It all began with the development of mustard gas and I’m sure we’ve all seen the awful pictures of solders leading each other from the battlefield having been affected by this ‘deadly cloud‘. Let’s hope we never have to witness that again. This weapon was first used 100 years ago this week (note: blog published in Apr 2015) but out of the horror came a ‘silver lining‘ – the idea behind what is now called chemotherapy.
However, the development didn’t really begin until the second world war when two doctors from Yale University (Louis Goodman and Alfred Gilman), conducted animal and then human trials. Then in 1948, UK scientist Professor Alexander Haddow published a ground breaking piece of research in the journal Nature, showing exactly which bits of the nitrogen mustard molecule were needed to kill cancer cells. Perhaps more importantly, he also found out how to make the chemical less toxic, but with more potent cancer-killing activity. So mustard gas went from the very real battleground of the WWI trenches into the frontline of cancer treatment where it still is today.
You can read more about this on the Cancer Research UK Science Blog
Chemotherapy and Neuroendocrine Cancer
One of the unusual aspects of Neuroendocrine Cancer is that chemotherapy is not normally considered as a ‘standard’ treatment unlike many other cancers. The exception is high grade (Grade 3) where it is often a first and/or second line therapy. Poorly differentiated Neuroendocrine disease is normally labelled as Neuroendocrine Carcinoma (NEC) but worth pointing out there is now a Grade 3 well differentiated classification known as a ‘Grade 3 NET’ rather than Grade 3 NEC. Depending on Ki67 score, there could be differing treatment options for Grade 3 NET and Grade 3 NEC. Read more in my article Staging and Grading.
The type of chemo or the combination of different treatments will often depend on the tumour type and anatomical location involved but may include (but 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). many as a combo treatment. There is a useful article explaining the role of Ki-67 in determining optimal chemotherapy in high grade neuroendocrine tumors.
Horses for Courses – Chemo is sometimes used for well differentiated lower grade NETs.
Cytotoxic chemotherapy is often inadequate for treatment of Grade 1 and 2 (well differentiated) Neuroendocrine tumours which have a low proliferation index. Chemotherapy does not appear to like their slow cytokinetic growth. However, it tends to work better on certain parts of the anatomy than others, e.g. pancreatic NETs and Lung NETs. Of interest is a statistic from NET Research Foundation indicating that 23% of patients who were to be prescribed chemo had their treatment changed to a non-chemo option following a Ga68 PET scan. Read more here.
For second line therapy (including for well differentiated NETs where other conventional treatments are not working), chemo may be given. These include (but not limited to) Capecitabine, Temozolomide, Bevacizumab, Xelox, Folfox. There are other specialist chemos for Mixed Neuroendocrine Non-Neuroendocrine Neoplasms (MiNEN).
Capecitabine plus Temozolomide (CAPTEM for short) is fast becoming the standarad chemotherapy treatment when it is required with certain lower grade NETs. Dr Robert Fine says the results of the CAPTEM trial showed “tremendous responses in every neuroendocrine tumor”. The treatment elicited a response rate of 45% and a stable disease rate of 52% including those with certain types of NETs and pituitary tumours – types of neuroendocrine tumour that are notoriously ‘chemoresistant’. You can read more about this here (click here) and you can also listen to Dr Fine enthusiastically talking about this on a short You Tube video clip – (click here). Clearly it is not going to work for all.
Other CAPTEM Resources:
- There’s a very interesting report on the use of CAPTEM in NETs – (click here)
- CAPTEM Trial Document – (click here)
PRRT and Chemo Combo Treatment
In Australia, they’re also using a combo treatment of chemo (CAPTEM) and PRRT – I blogged about this click here.
There’s also a useful surgical technique which includes the use of intra-operative chemo, known as “Chinese Dumplings” – I wrote about this click here.
My Oncologist did mention Chemotherapy on my initial meeting, that was a shock and realisation I had something serious. However, that never transpired but I was once scheduled to have a chemo-embolisation (or TACE, Trans-arterial Chemo Embolisation). Clearly TACE is more targeted than conventional and generally systemic chemotherapy techniques. Perhaps that my Oncologist actually meant. The chemo-embolisation never transpired either (long story).
Chemotherapy vs Targeted Biological Agents and Somatostatin Analogues
I often see people describing Somatostatin Analogues (Lanreotide/Octreotide), Afinitor (Everolimus) and Sutent (Sunitinib) as chemo but that’s isn’t technically correct, and I’ve yet to find a NET Specialist or a NET Specialist Organisation who classifies these drugs as chemo. See my article “Chemo or not Chemo” (click here).
Future of Chemo?
A lot is written about how much longer chemo will be around. It gets a bad press – I suspect mainly due to the side effects. There are suggestions that it will eventually be replaced by Immunotherapy and other treatments downstream. However, immunotherapy is really still in its infancy and there remains a lack of long term data on success rates and side effects. I suspect chemo will be around for a while longer, particularly for cancers where it has a track record of curing according to ASCO. Very recently (June 2018), cancer experts said that chemo will be around for a long time yet – read more here
None of the content of this post should be interpreted as advice or a recommendation for chemotherapy. If in doubt about suitability for any form of chemo, or the type you have been prescribed, patients should seek the advice of their treating doctor or NET specialist.
Thanks for reading