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. Systemic chemotherapy is often inadequate for treatment of Grade 1 and 2 Neuroendocrine tumours, because these tumours tend to have a well-differentiated histology and low proliferation index – standard chemotherapy does not appear to like their slow cytokinetic growth. However, chemotherapy appears to be frequently deployed for use with very advanced and/or high grade Neuroendocrine tumours (i.e. carcinomas). My Oncologist did mention Chemotherapy on my initial meeting and I was once scheduled to have a chemo-embolisation (TACE, Trans-arterial Chemo Embolization) but it never occurred due to post surgical routing issues. Clearly TACE is more targeted than conventional and generally systemic chemotherapy techniques.
However, chemo remains a first line treatment regime for Grade 3 NETs (Carcinomas). The NET Patient Foundation indicates several combo treatments are possible:
• Cisplatin + Etoposide
• Carboplatin + Etoposide
• Capecitabine + Temozolomide
• Temozolomide + Bevacizumab
Capecitabine plus Temozolomide (CAPTEM for short) have been trialled on low grade NETs though. Dr Robert Fine says the results of the 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 carcinoid 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).
New section added May 2016. A trial of ‘TEM’ and TAS-102. I picked up another piece of information about chemo for NETs in US. This trial is thanks to the good work of the The Aly Wolff Foundation. Aly Wolff died of neuroendocrine cancer on April 22, 2013, however her courageous battle continues. Today, three years later, a new clinical trial at the University of Wisconsin Carbone Cancer Center has been approved and holds great promise in offering a new line of treatment for those with neuroendocrine tumors. This Phase 1b trial, which is open to those with low or intermediate grade NETs of any tissue origin to determine the tolerable dose. Then, it will enrol pNET patients from across Wisconsin and, if more patients are needed, may include partner sites through the Big Ten Cancer Research Consortium. Patients will receive the chemotherapy for one year or until the disease progresses, whichever comes first. The trial will comprise a combination of temozolomide (the TEM in CAPTEM) and a newer drug, TAS-102, (related to capecitabine (the CAP in CAPTEM) but has a different mechanism of action). TAS-102 was approved for colon cancer patients last fall and many of those patients who no longer respond to capecitabine show a response to TAS-102. If this trial is successful, then we are one step closer to adding another line of therapy in treating neuroendocrine tumors.
In Australia, they’re also using a combo treatment of chemo (CAPTEM) and PRRT – I blogged about this here.
There’s also a useful surgical technique which includes the use of intra-operative chemo, known as “Chinese Dumplings” – I blogged about this here.
If in doubt about suitability for any form of chemo, patients should seek the advice of a NET specialist.
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