Edited and checked April 2021
One of the unusual aspects of Neuroendocrine Cancer is that chemotherapy is not normally considered as a ‘standard’ treatment unlike many other cancers. One 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 articles Staging and Grading and High Grade.
Many people think Chemotherapy has a short life span due to recent advances in medical science, some citing Immunotherapy as it’s replacement. However, it’s far too early to write off chemotherapy which is still used in many scenarios and remains a tool in the arsenal of cancer treatments and is predicted to do for some time yet. See more informed reporting about this below.
Which Chemo for which Neuroendocrine Cancer type and grade/differentiation?
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.
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).
‘Horses for Courses’ – Chemo is sometimes used for well differentiated lower grade NETs.
There’s a myth that circulates the NET patient forums along the lines of “chemotherapy does not work for NETs“. That’s not entirely true but most will not get chemotherapy, and this can often lead to confusion in those with Stage 4 cancer when asked by others why they are not receiving chemo.
Capecitabine plus Temozolomide (CAPTEM for short) is fast becoming the standard 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 talking about this on a short You Tube video clip – (click here). It’s true that it’s not going to work for all.
Other CAPTEM Resources:
- There’s an interesting 2018 report on the prolonged use of CAPTEM in NETs – (click here).
- CAPTEM Trial Document – (click here).
- This single centre study from 2018 is also useful. (click here).
PRRT and Chemo Combo Treatment
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-embolization (or TACE, Trans-arterial Chemo Embolization). Clearly TACE is more targeted than conventional and generally systemic chemotherapy techniques. Perhaps that was what my Oncologist meant. The chemo-embolization never transpired either (long story). Read more about liver direct therapy here.
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).
Platinum-based drugs (informally called platins) are chemotherapeutic agents used to treat many types of cancer including Neuroendocrine. These drugs are used to treat almost half of people receiving chemotherapy for cancer. Commonly used chemo includes Cisplatin, Oxaliplatin, and Carboplatin.
Other Cytotoxic chemo include:
- Fluorouracil (5-FU),
- Streptozotocin (Zanosar)
- Irinotecan (Campto)
- Paclitaxel (Taxol)
and the oral (tablet) versions:
- Capecitabine (Xeloda),
- Temozolomide (Temodal),
- Etoposide (Etopophos, Vepesid)
Known combos used in NENs.
Cisplatin and Etoposide appear to be the most commonly used combo for high grade.
Capecitabine (Xeloda) and Temozolomide (Temodal) (CAPTEM) are used in cases of Grade 2 and Grade 3 NET but also listed as a second- or third-line treatment for NEC.
FOLFOX. Also known as Oxaliplatin de Gramont or OxMdG, which means modified Oxaliplatin de Gramont. It is made up of folinic acid (also called leucovorin, FA or calcium folinate), fluorouracil (5FU) and oxaliplatin.
FOLFIRI. Also known as irinotecan de Gramont or irinotecan modified de Gramont. It includes folinic acid (also called leucovorin, calcium folinate or FA), fluorouracil (5FU) and irinotecan.
FCarboSt. A combo of Fluorouracil, Streptozocin and Carboplatin. Use may be limited to Royal Free Hospital London. Would love to hear from others.
Future of Chemo?
A lot is written about how much longer chemo will be around. It gets a bad press – I suspect due to the side effects. There are suggestions that it will eventually be replaced by Immunotherapy and other treatments downstream. However, immunotherapy is 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.
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