CAPTEM for Neuroendocrine Tumours

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What is CAPTEM? 

Capecitabine is an oral drug used alone or with other drugs to treat certain types of colorectal cancer and breast cancer. It is also being studied in the treatment of other types of cancer including in combination with a second drug. Capecitabine is taken up by cancer cells and breaks down into fluorouracil, a substance that kills cancer cells. Xeloda is a type of antimetabolite. Also called Xeloda.

Temozolomide is an oral drug used to treat adults with certain types of brain tumors. It is also being studied in the treatment of other types of cancer including in combination with a second drug. Temozolomide damages the cell’s DNA and may kill cancer cells. It is a type of alkylating agent. Also called Temodar.

Capecitabine (brand name Xeloda) plus Temozolomide (brand name Temodar) (CAPTEM for short) is fast becoming the go-to chemotherapy treatment when it is required with certain scenarios in NETs, particularly pancreatic NETs.  Both drugs can generally be classified as chemotherapy.

I frequently see the well-known myth going around patient groups along the lines of “chemo doesn’t work for Neuroendocrine Cancer, right?”  WRONG.  This is a result of years of misunderstanding of the heterogeneous nature of Neuroendocrine Cancer and the lack of moderation in patient online groups. For example, first (and second) line treatments for Neuroendocrine Carcinoma (high grade poorly differentiated) tend to be chemotherapy.  Additionally, it has some utility in some well-differentiated NETs, as I am about to prove.  Going forward, I’m only going to talk about well-differentiated NETs as the established standard of care for Neuroendocrine Carcinoma (NEC), in terms of chemotherapy, is well documented in guidelines.  However, I may update this post in due course with authoritative data on the use of CAPTEM for NEC. 

What is the origin of CAPTEM use in NET? 

Looking at research online, it would appear much of the groundwork was carried out by Dr Robert Fine (Colombia University) who had been researching the use of CAPTEM in NETs for some time.  He finally went public around 2013/14 with published data from a small Phase 2 trial indicating “tremendous responses in every neuroendocrine tumor”.  You can listen to Dr Fine discussing the results in a short YouTube video clip – (click here).

It’s true that it’s not going to work for all. It’s also true to say that Dr Fine’s work was based on a small number of patients, nonetheless, the data is rather good in comparison to other NET treatments. It must also be noted that Dr Fine focussed on those NET patients whose advanced disease, particularly liver metastases, had worsened after standard high-dose octreotide. This was a prospective study, i.e. it watched for outcomes over a period of time.

However, different types of trials can offer better evidence, e.g. a randomised controlled trial is a prospective, comparative, quantitative study/experiment performed under controlled conditions with random allocation of interventions to comparison groups. The randomised controlled trial is the most rigorous and robust research method of determining whether a cause-effect relation exists between an intervention and an outcome. Since Dr Fine’s work, there have been several other CAPTEM studies, some single institutions but also showing relatively good results.  I will focus on one in particular below. 

So why am I writing about CAPTEM now? 

It was a highlight of the recent ASCO 2022 conference (the biggest Oncology conference in the world) and it was highlighted by several NET specialists as one to watch.  The data was presented by Dr Pamela Kunz, well known and respected NET expert.  It was the final report on a Phase 2 trial looking at pancreatic NETs.  And it was a randomized study of temozolomide or temozolomide and capecitabine in patients with advanced pancreatic neuroendocrine tumors: Final analysis of efficacy and association with MGMT (ECOG-ACRIN E2211).

The results show that the response rate (RR) was 34% for temozolomide and 40% for capecitabine/temozolomide. The conclusion statement is as follows:

Conclusions: E2211 is the first prospective randomized trial of capecitabine/temozolomide and shows the longest PFS and highest RR reported for patients with pancreatic NETs in a prospective randomized study. MGMT deficiency was associated with greater odds of objective response. Clinical trial information: NCT01824875.

Finally, you can listen to Dr Kunz eloquently explain this trial and its background and results, and more importantly what it could mean for CAPTEM going forward.

Click on the picture to watch:

Picture from The ASCO Post

Click on the picture to watch a short video (5 minutes)

Standard of Care

One of the key things Dr Kunz said is that CAPTEM should really be what doctors call a “Standard of Care (SoC)” treatment for well-differentiated NETs (I will initially assume the inference is for pancreatic NETs given the clinical trial being discussed).   SoC is also called best practice, standard medical care, or standard therapy.  You will note from some NET guidelines that it’s not listed as an option, e.g. in the NCCN guidelines, you will only find CAPTEM mentioned in referred studies.  In ENETS guidelines, you may see Streptozocin (Zanosar) in a combo with Fluorouracil (5-FU) for use in a similar range of patients.  See this 2020 document from Germany here.

There is interesting comment from the ASCO Post from Dr Pamela Kunz but also from Dr Marianne Pavel who gave a European outlook on the trial.  Interestingly Dr Pavel said “Putting the study into context with previous prospective randomized studies in pancreatic neuroendocrine tumors, temozolomide with or without capecitabine has produced the best response rates and overall survival among evaluated therapies in patients with progressive pancreatic neuroendocrine tumors. Now, in ECOG-ACRIN E2211, capecitabine/temozolomide has resulted in “the best response rates, the most durable progression-free survival, and the best overall survival ever reported in this patient population”. But she added that some questions remain. 

You can read both commentaries here:

ASCO Post – Dr Kunz – click here

ASCO Post – Dr Pavel – click here

What’s next?

That is an interesting question, and I will leave this section blank until more information is issued following ASCO 2022.

Side Effects of CAPTEM?

As usual with any cancer drug, there can be side effects.  Not everyone will get side effects, some may get particular ones and others may not get that at all. 

The following links will take you to the listed side effects for both using tablet form (oral):

Side effects of Capecitabineclick here

Side effects of Temozolomideclick here

The drug can also be given via IV, the listed side effects may be different. 


Whenever I post about a trial or study, some people get excited without understanding that these new treatments and capabilities can very often take years to come to fruition and it’s also possible that clinical trials can be halted, or that national approval agencies will not approve the final product.  Plus, not everyone will be eligible, so always check the exclusion and inclusion criteria in the relevant clinical trials document  Please bear that in mind when reading studies/clinical trials posted on RonnyAllan.NET


I am not a doctor or any form of medical professional, practitioner or counsellor. None of the information on my website, or linked to my website(s), or conveyed by me on any social media or presentation, should be interpreted as medical advice given or advised by me. 

Neither should any post or comment made by a follower or member of my private group be assumed to be medical advice, even if that person is a healthcare professional.   

Please also note that mention of a clinical service, trial/study or therapy does not constitute an endorsement of that service, trial/study or therapy by Ronny Allan, the information is provided for education and awareness purposes and/or related to Ronny Allan’s own patient experience. This element of the disclaimer includes any complementary medicine, non-prescription over the counter drugs and supplements such as vitamins and minerals.

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