A team of radiologists and respiratory consultants who introduced a new and more efficient lung biopsy method at Barnet Hospital London, has been named the winner of the NHS Innovation Challenge Prize in the ‘cancer care’ category. Barnet Hospital is run by the Royal Free London NHS Foundation Trust which is well known for its Neuroendocrine Cancer Centre of Excellence.
Not happy with this, they’ve now gone on to introduce a new service combining this innovative biopsy system with Radio Frequency Ablation (RFA) of tumours in the same procedure.
Combined Biopsy with Radio Frequency Ablation (RFA)
This new service has significant advantages for those who have localised tumours less than 3cm and can’t for whatever reason have surgery. I’ve checked with Dr Hare and he confirms this includes Neuroendocrine Tumours of the Lung. There are a number of advantages for having this procedure:
1. Biopsy and RFA at same time to prevent patient having to have 2 procedures. Those who meet this criteria with an existing biopsy can go straight to RFA.
2. It’s a low risk, minimally invasive procedure.
3. As its under mild sedation rather than General Anaesthetic (GA) – patients go home later the same day – makes recovery time so much quicker.
4. RFAs can be repeated as many times as you want if tumour ever grows.
5. Lungs are preserved.
It’s also worth noting that RFA as a standalone treatment can be used on lung metastases. You can read more about this new service here.
Award winning ambulatory lung biopsy service
The team’s innovative ambulatory lung biopsy service enables the vast majority of patients to be discharged just 30 minutes after their biopsy. Dr Hare is a pioneer in UK lung biopsy technique and has improved patient experience using a shorter, less painful biopsy process with a higher diagnostic accuracy and less time spent in hospital. Dr Hare specialises in image-guided lung biopsy techniques having gained expertise in the procedure working in North America. Dr Hare’s innovative use of a Heimlich Valve Chest Drain (HVCD) allows more successful biopsy of small lung nodules which can potentially lead to earlier cancer diagnosis.
I spoke to Dr Hare via twitter and he confirmed this novel service is for any tumour in the lung (primary or metastasis) and he indicated they were “finding more and more are coming back as Neuroendocrine Tumours”.
You can read more about Dr Hare and his work here (www.lungdiagnosis) and this video explains it in excellent detail including the difference between conventional methods and this new ‘award winning’ way! Read more about the award on the Royal Free site here.
Congratulations to Dr Hare and the rest of the team for winning this award!
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When I was diagnosed, I wasn’t feeling ill. In hindsight, I now know some of the signs were there, I just put up with them. Neuroendocrine Cancer had laid a trap for me and I fell right into it. You see, Neuroendocrine Cancer can be very quiet and unobtrusive. It also plays the ‘long game’ and will sometimes take years before it’s finally discovered. It is very very very sneaky.
Not satisfied with loitering in your small intestine, appendix, lungs, stomach, pancreas and a host of other places, it wants to reach out to your liver, your lymph nodes, your bones, bung you up with fibrosis, and get into your heart where it can cause the most damage. It will also try to get into your head, metaphorically speaking – however, it will also try the physical route.
As it spreads, it can become noisier through growth but also by secreting excess amounts of hormonesand other substances. It knows that tumour growth and these excess hormones and substances will mimic routine illnesses such as IBS, diarrhea, stool changes including steatorrhoea, stomach cramps and bloating, asthma, facial flushing, menopause, weight loss, anaemia, fatigue, tachycardia (fast heart beat), pain, and nausea – a real witch’s brew of symptoms. These may manifest themselves as common endocrine conditions e.g. it can mess with your blood sugar and thyroid levels. These are a few examples, there can be many others – it’s a real witch’s brew of symptoms. Neuroendocrine Cancer thinks this is great because it fools doctors into misdiagnosing you with something else which means it can continue to grow undetected and unfettered, spreading further inside you.
If nothing is done to stop its relentless growth, it will eventually kill.
However, sometimes an inquisitive doctor or nurse upsets its progress by thinking ‘outside the box’. Neuroendocrine Cancer hates when people are aware of its devious nature and hates when people know which tests can be used to find it and which treatments are best to attack it. Inquisitive, proactive and determined patients can also add to this effect and sometimes a bit of luck is involved.
It doesn’t give up easy and tries to work around your treatment. It knows your treatment will come with certain consequences and it will try to exploit this situation by keeping you guessing between cancer activity and these consequences. It really hates observant medical staff and patients, particularly those who understand Neuroendocrine Cancer.
Unfortunately for Neuroendocrine Cancer, there is now more knowledge about its devious activities and the latest statistics indicate it’s starting to be caught earlier. Nonetheless, we cannot afford to become complacent.
Neuroendocrine Cancer hates awareness and it will be extremely happy if you don’t share this post.
Social Media is currently full of ‘Dry January’ articles and of course many charities will benefit as people will be motivated if they are abstaining from alcohol for a good cause. Nothing wrong with that and no doubt some individuals will also see it as a way to cut down or at least lessen the effects of a very wet December!
I’ve never been a big drinker but I do like the odd beer now and then. When I was diagnosed with metastatic Neuroendocrine Tumours (NETs), I hadn’t really thought much about how this might affect my body. It wasn’t until I studied a bit more about my disease and the consequences of my treatment, that I decided I would cut right down. This turned out to be a pretty drastic cut as I can count the number of alcoholic drinks I consumed in the past year on one hand.
So what’s the deal with alcohol and Neuroendocrine Cancer?
There are some who might say that any alcohol is not good for any cancer patient. However, if your digestive system and your liver have been compromised by both disease and treatment, then is it perhaps best not to ‘stoke the beast’? In fact, there are specific references to alcohol and its potential effect on a Neuroendocrine Cancer patient, particularly those who suffer from the syndromes associated with Neuroendocrine Cancer, e.g. Carcinoid Syndrome.
Alcohol is frequently mentioned as a trigger for Carcinoid Syndrome symptoms particularly flushing and this is possibly due to the levels of ‘syndrome triggering amines’ that it contains. It is in fact one of the 5 E’s using its synonym of ‘Ethanol’. Many of us do feel a warm sensation in our faces (and beyond) when we drink alcohol as it can dilate blood vessels. On the basis that some will react worse than others (…flush), then you can see why alcohol can be a trigger for flushing. However, despite other reasons existing for alcohol related flushing, these triggers can often be important clues in diagnosing carcinoid syndrome. Alcohol is second only to large meals in the list of foodstuffs reported to provoke reactions according references here.
But the odd beer does not make me flush?
I guess I’m lucky in that respect as I have read stories from people who cannot tolerate a single drop! But there is another reason why I will not be rushing down to the pub to ‘sink a few’ and I guess this could apply to anyone who has a compromised system. Food in your diet (and this includes alcohol) must be digested before being absorbed by your cells. The problem with alcohol however, is that it flows directly through your body’s membranes into your bloodstream and your bloodstream carries alcohol to every organ in your body. I don’t really want to add too much fuel to the smouldering remains of my body.
However, like anything in life, you can assess and then manage and mitigate the risks associated with an activity. Things that can be potentially harmful in large amounts can still be enjoyable with disciplined moderation. So, I will still be maintaining my very conservative alcohol regime but I doubt I will ever hit double figure beers in a single year. A beer is now a very special treat at Birthdays, New Year, ‘Cancerversaries‘ and special holidays …….a reminder that I still live.
From ASCO 2019 conference extract: Of the 17 patients enrolled, 16 completed the 12-week trial. One patient was not evaluable due to noncompliance. No DLTs were observed at day 21. The highest dose of 10 mg daily oral everolimus in combination with weekly 60mg/m2 IV fosbretabulin is the RP2D. No grade 4 or 5 toxicities were noted. Grade 3 toxicities were seen in 5 patients; abdominal pain and hyperglycemia (not related to study drug), fatigue (possibly related), decreased lymphocyte count and anemia (related). Several patients had delay in treatment due to grade 2 AE’s (GI symptoms, rash, thrombocytopenia) and one patient was unable to complete treatment due to pneumonitis. All evaluable patients except one had stable disease at 3 months. One patient showed SD but non target lesion demonstrated PD. One patient had > 30% decrease in tumor size but overall sum of lesions showed SD. A detailed table with all grade toxicities and waterfall plot of RR will be presented at the meeting. Ten mg PO daily everolimus plus 60 mg/m2 fosbretabulin IV weekly is the RP2D. Early clinical data suggests clinical activity and stable disease in all but one patient at 3 months. Read full text from ASCO 2019 here.
For further information about the clinical trial, please visit www.clinicaltrials.gov, Study NCT03014297
I will get a better picture but this is what they tweeted from ASCO 2019
added 19 Apr 2017
Mateon Therapeutics, Inc. a biopharmaceutical company developing vascular disrupting agents (VDAs) for the treatment of orphan oncology indications, today announced that the Markey Cancer Center at the University of Kentucky has enrolled the first patient into a new phase 1 study of CA4P in combination with everolimus for the treatment of neuroendocrine tumors.
“The combination of CA4P and everolimus has the potential to decrease the ability of tumor cells to recover between CA4P treatment cycles,” stated Lowell B. Anthony, M.D., Professor of Medicine and Chief, Division of Medical Oncology, Markey Cancer Center, University of Kentucky. “This is the first trial testing this hypothesis in neuroendocrine tumors – with CA4P disrupting the existing tumor blood supply and everolimus preventing a new tumor blood supply from re-forming. Our findings from this trial should lead to a larger clinical study once we have identified the optimal dose and schedule for the combination of these two agents.”
Study MCC-2016-088 is designed to demonstrate whether the addition of CA4P to everolimus may improve tumor control without additional toxicity. Everolimus has been approved by the U.S. Food and Drug Administration for the treatment of advanced pancreatic neuroendocrine tumors and progressive gastrointestinal neuroendocrine tumors, among other indications, and is marketed by Novartis under the tradename AFINITOR®. Mateon has previously demonstrated initial evidence of efficacy for CA4P in patients with neuroendocrine tumors when CA4P was provided as a single agent.
Study MCC-2016-088 is being sponsored, funded, and conducted by the Markey Cancer Center, with Mateon providing the investigational drug. The study is designed as a single center, open label, phase 1 clinical trial for patients with grade 1-3 gastroenteropancreatic neuroendocrine tumors. In the first part of the study, up to 15 patients will be treated with everolimus in combination with two different dosing regimens of CA4P to establish appropriate CA4P dosing levels and evaluate the safety of the drug combination. The second part of the study is designed to enroll 15 additional patients for assessment of additional safety and efficacy data. Patients enrolled in MCC-2016-088 will be treated with CA4P and everolimus for 12 weeks.
For further information about the clinical trial, please visit www.clinicaltrials.gov, Study NCT03014297. (see also ‘added 23 Dec 2016’ below)
added 23 Jan 2017
Mateon Therapeutics, a biopharmaceutical company developing vascular disrupting agents (VDAs) for the treatment of orphan oncology indications, today announced the presentation of final data from Study OX4218 in patients with neuroendocrine tumors (NETs) at a poster session at the ASCO Gastrointestinal Cancers Symposium being held today in San Francisco (20 Jan 17).
Study OX4218 was a multi-center, open label, phase 2 clinical trial to investigate the safety and activity of combretastatin A4-phosphate (CA4P) in the treatment of well-differentiated, low-to-intermediate-grade unresectable, recurrent or metastatic pancreatic or gastrointestinal neuroendocrine tumors/carcinoid (PNETs or GI-NETs) with elevated biomarkers. Following patients’ completion of Study OX4218, patients were eligible to enroll in Study OX4219, a long-term extension study, if they achieved a biomarker or symptom response. In OX4218 patients were treated with CA4P 60 mg/m2 on Days 1, 8, and 15 of a 21-day cycle for 3 cycles, and in OX4219 patients received CA4P maintenance on Day 1 of a 21-day cycle until disease progression or up to one year.
A total of 18 patients were enrolled in OX4218. One patient (6%) experienced significant symptomatic improvement as measured by ECOG Status and had a partial response per investigator-assessed RECIST and an additional 7 patients (39%) had stable disease. In addition, a majority of patients (53%) experienced an improvement in patient-reported quality of life. A statistically significant mean change in biomarkers from baseline, the primary endpoint of the study, was not achieved in OX4218 due to the small sample size along with a high intra- and inter-patient variability observed in the biomarkers. A total of 7 patients were enrolled in OX4219, of which 5 patients (71%) had stable disease, including one that continued for 14 months. The partial response and stable disease analyses, as well as other measures from the trial, suggest that CA4P monotherapy has activity in this indication.
“The results of OX4218 and OX4219 confirm that CA4P monotherapy has efficacy in the indications studied, as we have seen with the investigational drug in a number of other monotherapy trials,” said William D. Schwieterman, M.D., President and Chief Executive Officer of Mateon. “However, we believe that the efficacy of CA4P only becomes compelling when it is used in combination with an anti-angiogenic agent, due to the complementary mechanisms of action for the two agents. Based on the evidence of efficacy observed in this trial, plus an understanding of the benefits of combination therapy, a lead investigator in this trial is sponsoring a 20 patient study in NETs using CA4P in combination with everolimus (AFINITOR®, marketed by Novartis), an anti-angiogenic agent which is already approved and commonly used in this indication.”
Overall CA4P monotherapy was well tolerated. Treatment related adverse events were reported in 77% of subjects. The most common Grade 3-5 AEs (>10%) included: anemia, abdominal pain, fatigue, hypertension, and ALT and AST increases. One Grade 5 adverse event, carcinoid syndrome, was reported and attributed to the underlying disease.
added 23 Dec 2016
There is news of a trial involving this drug which I first published in Jan 2016. The trial is based at Markey Cancer Centre and is led by Dr Lowell Anthony. The trial’s primary objective is to establish the maximum tolerated dose of the combination of Everolimus (Afinitor) plus Fosbretabulin in Neuroendocrine Tumors (Grades 1-3) who have progressed after at least one prior regimen for metastatic disease. Read more here.
The original blog published on 10 Jan 2016 follows:
It’s always nice to hear that another treatment for Neuroendocrine Cancer is in the pipeline. This drug is in the news because it has just been granted designated orphan drug status by the FDA in the US for the treatment of Neuroendocrine Tumours.
My initial thoughts are that it looks promising but it’s very early days.The new drug is formally known as Fosbretabulin Tromethamine or just Fosbretabulin.It also goes by the name of Combretastatin or CA4P which translates to Combretastatin A4-phosphate.In the most basic of terms, it’s a type of vascular disrupting agent (VDA) (note – it’s not chemotherapy).
It appears to be something currently targeted at patients with Advanced Pancreatic or GI Neuroendocrine Tumours with elevated biomarkers. This is not a new drug and has been around for some years. According to Cancer Research UK, it has already been used for advanced and recurrent ovarian and thyroid cancers.
So how does it work? The drug makes the cells that line the smallest blood vessels (capillaries) swell up and this has the effect of blocking the blood flow to a tumour. All tumours need a blood supply so that they can get the oxygen and food they need to survive and Neuroendocrine Tumours can be highly vascular. It follows that if the blood flow to a tumour is blocked, there is a chance that it could stop growing or at best kill the tumour (necrosis). Sounds like the same principles used in Liver Embolization except that this drug has a greater anatomical reach plus a vastly different delivery mechanism via a 10 minute IV infusion.
So why is it a targeted treatment? The drug will only affect blood vessels that supply cancer cells. Cells lining normal blood vessels contain a protein called actin and this protects the blood vessels from the drug’s effects. Cells lining blood vessels that supply a cancer don’t have actin.
Does it work alongside other treatments? Interestingly, it appears to be a recommendation to use the drug in combination with anti-angiogenic drugs (i.e. those that can stop the growth of new blood vessels rather than block the blood supply). Also, according to the manufacturer Mateon, Fosbretabulin has demonstrated broad potential therapeutic value when combined with mainstay oncology modes of treatment including chemotherapy, radiation therapy and the more recent ‘molecularly-targeted therapies’. In fact if you read the trial addition above dated 23 Dec 16, you will see it’s being tested alongside Everolimus (Afinitor).
So when can we expect to see this drug? Phase 2 trials were completed at the end of 2016 (results above). I guess it would still be some years ahead if they wish to proceed. You can see the trial information by clicking here.
I’ll keep this blog live adding to it when I find new or updated information.
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The WordPress.com stats team have prepared a 2015 annual report for my blog. Special thanks to those who got a mention! Why not review my posts which received a 2015 Mention in Despatches ?
Here’s an excerpt:
Madison Square Garden can seat 20,000 people for a concert. This blog was viewed about 62,000 times in 2015. If it were a concert at Madison Square Garden, it would take about 3 sold-out performances for that many people to see it.