Search Results for 'gemcitabine cisplatin'

Hey all,

Thought I’d revive this thread after a little time off!

Just to update you on the situation with my dad (Martin).

So, at our previous consultation in April with the Leeds Oncologist, they decided NOT to proceed with Chemo and wait a little longer to see how the cancer fared over the next 3 months.

Upon questioning why they would want to wait rather than just go ahead the response was the following.

“There is currently only one type of chemotherapy treatment that is known to be effective for CC patients, that is the Gemcitabine and Cisplatin regimen. The chemotherapy was shown to be effective in shrinking the tumours around 60% of the time but it would never completely cure the cancer. Therefore each subsequent round of chemo was found to be less effective than the last as when the cancer regrows it does so with an added tolerance, until eventually it is no longer affective. This varies from patient to patient, in some cases they could go through 4 or 5 round over a number of years, but in some cases it wasn’t effective at all.”

Therefore, given that my dad’s Cancer is “slow growing” and he was in good health, the decision was to hold off on treatment until there was evidence of more significant growth in the hope that the chemo would have more to target and thus be more effective.

I have to say, I didn’t really agree with this at all, it seemed very ‘reactive’ rather than ‘proactive’. I mean if you have a leaking roof, you don’t wait until the house is flooded before cleaning it up, you fix it immediately to minimize the damage… but hey what do I know I’m just a Construction Manager.

Anyway, around the end of July/beginning of August dad’s bowel movements started to become irregular (i.e very often), he was showing signs of Jaundice and weight loss. He went to our local GP who took some blood samples and stool samples to test for infection and his Bilirubin levels. In the meantime he was prescribed some antibiotics. Blood tests results showed no signs of infection but Bilirubin Levels were up from ‘normal’ 20-30 to 95.

As he was scheduled for his quarterly scan at St James anyway this information was passed over to them. A week or so later Dad had his CT scan and more blood tests. All the time dad’s starting to feel worse, getting very emotional, unable to sleep at night due to constant Diarrhea, generally quite emotional and drained of energy. Another week passes before the consultation with firstly the Leeds Surgeons and Oncologists to discuss his scans and blood tests. However it is decided that a ultrasound scan would be done before the meetings.

Monday 19th August, we go to Leeds for the Ultrasound Scan and to see the Surgeons. On this occasion we didn’t see the general surgeon Mr Prasad, but one of his new understudy’s, who was not at all familiar with his case, In fact she asked us to talk her through the case!! Perhaps it’s just me but I was actually quite shocked by this.

Both CT Scan and Ultrasound scan show once again showed ‘no significant growth’ (they love that term) in the existing tumours, and no new mets. So from a surgical point of view they didn’t believe there was any work to be done (i.e no need for a stent or any other surgical treatment). So his case was passed on to the Oncologist to discuss further. More blood samples were taken.

We returned on Tuesday morning to see the Oncologist. This time, we saw Dr Anthony, he was far more up to speed with the case and actually talked us through the scans which we were loaded up on his computer.
The scans showed that that over the course of 11 months since the recurrent tumours were first spotted, the 2 lesions in the liver had each grown approximately 10mm in 11 months and were approximately 31mm and 38mm in size. However, these lesions were situated in areas of the liver far from any bile ducts and were unlikely to cause any blockages or be responsible for his recent symptoms. He expected that for these tumours to cause any significant problems they would need to be 5 times the size. The mets in the lung were negligible and not of much concern.

The decision was made that now would probably be the right time to start chemo, but also an MRI scan would be done beforehand to see that would give a clearer picture of what’s going on in his bile ducts as all symptoms point towards a blockage. To quote him “We don’t want to be lured in to a false sense of security based on the Ultrasound and CT”.Blood tests showed a steady rise in bilirubin which was now at 112 up from 95. We were told that we would hear back regarding a scan in the next couple of days before the August bank holiday.

The Week Passes and no word, Dr Anthony is on holiday for the whole week commencing 26th August but on the 29th a letter is received via our local GP. My dad’s Bilirubin Levels are now at 195 (up from 112). A meeting is arranged for Tuesday 3rd September with Dr Anthony.

Meeting on 3rd is held, Dr Anthony is surprised that my dad has not had his scan yet (he thought it would take place while he was on leave) and so arranges an MRI for next Thursday 12th September, with results to be discussed on Tuesday 24th September (two months since symptoms first started). Not much further to discuss, other than my dads lower left abdominal region which was in pain/aching. Dr Anthony suggested that this could be due to his bowel being in a strange place so waste gets trapped causing discomfort. When queried about the rise in Bilirubin levels Dr Anthony seemed unconcerned and said that Bilirubin levels need to reach 600+ before they become dangerous.

Anyway, since April my dad stopped taking the hemp oil (it made him very drowsy and tired), given that the hospital had no prescribed any medicine he started taking again. For the first time in 5-6 weeks he was able to sleep through the night without having to get up repeatedly for the toilet. We have also bought some supplements to aid liver functions as I read milk thistle and NAC can help?

Being able to sleep has obviously raised his energy levels. He is still working full time and playing golf at weekends, although he admits he was flagging on the back nine and gets tired in the afternoons.

I find it incredibly frustrating how long things seem to take with the NHS and can’t help but feel that all this waiting around not knowing is doing my dad no help at all both mentally and physically. I’m certain that if we had the money we would go private. I appreciate that they have other patients to see and they’re under resourced but 2 months is just a complete farce in my mind.

Dan

hmm. I think it is one of those things that you can have access to if you go through google first.

Do a google search on the title and then click on the top link and I bet that will work.

If you are google impaired, not to worry! it is just a Q&A. Here is a copy / paste. Please delete if it is against site policy to post this.

Jason

EDIT – Upon further review, you may have to sign up for a medscape acct. It is free at least.

Early Diagnosis Is Critical

Medscape: What are the main challenges in cholangiocarcinoma?

Dr. Kerr: Diagnosis comes too late. The majority of cases are too far advanced for complete removal. Often, all we have is limited palliative treatment. Unless we can diagnose cholangiocarcinoma early and recommend complete surgical resection, there is no curative therapy. Chemotherapy and radiation therapy have important but limited roles in palliation, with slight prolongation of life and slight improvement in symptoms, but we have a serious lack of therapeutic options when the disease presents at an advanced stage.

The epidemiology of cholangiocarcinoma is still somewhat opaque, but we know that such diseases as primary biliary sclerosis, a relatively rare inflammatory condition, cause a narrowing of the bile duct system that is associated with increased risk. More attention is being paid to screening and watching carefully over patients with primary biliary sclerosis for early signs of cancer so that we can offer surgical intervention.

The incidence of cholangiocarcinoma is only 1-2 per 100,000 persons, so no population screening program would be even remotely cost-effective.

Medscape: Are there any early warning signs of cholangiocarcinoma?

Dr. Kerr: Many cases are relatively silent clinically until they are quite advanced. The presentation at that point is typically jaundice, often accompanied by pain. Usually, the primary care physician would quickly refer a patient presenting with jaundice for a thorough work-up with ultrasonography, endoscopic retrograde cholangiopancreatography (ERCP), or whatever is required, but the patient who presents with vague upper abdominal pain is more likely to spend some time in primary or community care with painkillers, antacids, or a whole host of other reasonable over-the-counter therapeutic options. Often by the time the patient presents with jaundice, the disease may be too advanced for complete resection.

Specialist Multidisciplinary Teams Improve Care

Medscape: What is the standard of care for operable cholangiocarcinoma?

Dr. Kerr: Ideally, best care would include rapid referral of patients who have undergone the appropriate diagnostic and staging procedures, such as ERCP. There is an emerging trend for using endoscopic magnetic resonance pancreatography, but relatively few units have that technology. The main thing is that the patient be referred to a specialist center with good liver surgery facilities that are well supported by good imaging and radiology departments. I have no doubt that we have benefited in Oxford from having a multidisciplinary specialist hepatobiliary cancer team with leading surgeons, plus support from committed radiologists, pathologists, medical and radiation oncologists, and specialist nurses, all of whom want to drive the research agenda forward.

I don’t think that there is yet a proven role for either adjuvant chemotherapy or adjuvant radiation therapy in cholangiocarcinoma. In the absence of sufficiently compelling trials, this would be a non-evidence-based intervention and therefore not something one would recommend.

We urgently need more trials in the adjuvant setting following successful or presumed successful surgical resection.

Management of Unresectable Disease

Medscape: What is the standard of care for unresectable cholangiocarcinoma?

Dr. Kerr: The most compelling study was the one by Valle and colleagues[1] comparing cisplatin/gemcitabine vs gemcitabine alone for biliary tract cancer. This well-designed, 400-patient randomized trial showed a significant survival benefit of about 3.5 months for the cisplatin/gemcitabine combination. That is the best evidence we have for combination chemotherapy in advanced cholangiocarcinoma, so at the present moment I think that cisplatin/gemcitabine should be the gold standard for treatment.

There continue to be many phase 2 trials with various chemotherapy couplets,[2,3] sometimes with epidermal growth factor receptor kinase inhibitors,[4,5] with some interesting results. The problem is that for any phase 2 trial, there is a risk for selection bias, so we must not overinterpret those results.

Medscape: What is on the horizon for cholangiocarcinoma?

Dr. Kerr: Because of the drive toward personalized medicine and interest in use of biomarkers to select patients for particular types of drugs, Big Pharma is now paying more attention even to relatively rare tumor types, such as cholangiocarcinoma. For example, MET is a receptor tyrosine kinase triggered by hepatocyte growth factor, and the MET signaling pathway is associated with invasive growth. MET inhibitors are being investigated in several cancers, and it has been estimated that up to 58%% of cholangiocarcinomas have elevated levels of MET expression,[6] so MET inhibitors could be interesting to look at. Over 9% of cholangiocarcinomas also carry the ROS mutation[7] and might be candidates for treatment with ROS inhibitors, such as Pfizer’s lung cancer drug Xalkori® (crizotinib), which is also a MET inhibitor and might provide a double-whammy.

Medscape: What about new techniques, such as hepatic transarterial chemoembolization (TACE)?

Dr. Kerr: TACE has seen more rapid development in the Far East, where some studies have suggested interesting response rates in small numbers of patients treated with combinations of cytotoxic drugs and TACE. There are still no randomized trials, and most of the work with TACE has been in primary hepatocellular carcinoma, not cholangiocarcinoma. There are interesting case reports and early studies, but no compelling data that would cause us to take that up more widely.

The Search for Effective Targeted Therapies

Medscape: Have there been any recent surprises in cholangiocarcinoma research?

Dr. Kerr: The biomarker work is becoming very interesting. Looking at the molecular genotype, we are seeing quite a number of mutations. This should allow us to more accurately identify patients with cholangiocarcinoma who might benefit from the new drugs.[8,9] Although cholangiocarcinoma has always been an orphan tumor type, we are seeing much better genomic research that is already starting to throw out some interesting new targets.

Take the ROS mutation as an example. Crizotinib, which has been approved in the United States for treatment of certain types of late-stage, non-small cell lung cancer, appears to be a pretty effective drug. If the same mutation occurs in a different context, such as cholangiocarcinoma or colorectal cancer, are we likely to see the same level of effectiveness?[7] That’s at the cutting edge of translational cancer research.

Medscape: So you expect to see advances despite the rarity of the tumor?

Dr. Kerr: Exactly. We have also developed interesting collaborations, such as the INDOX trial network, which sees 100,000 new cases of cholangiocarcinoma each year. This is a beautiful model for bringing together East and West, combining the technology and genomic power in the West and the tumor types that are a more serious disease burden in emerging and developing countries.

Medscape: What is the most important unanswered question in cholangiocarcinoma?

Dr. Kerr: The most urgent is whether the cisplatin/gemcitabine couplet will be useful as adjuvant therapy, because it seems to be the most active treatment that we’ve got for advanced disease. I’d also like to see greater international collaboration to link the phenotype of the cancers with their genetics so that we can see whether there are subgroups likely to benefit from targeted therapies.