Pleural Mesothelioma - Chemotherapy questions - 1266676

Mike,

I'm very sorry about your brother's diagnosis. We're happy to try to help but in the interest of time, it's only feasible to cover the more central questions, not the ones that are not relevant to treatment.

The standard chemotherapy treatment is definitely cisplatin and Alimta (pemetrexed), most commonly given every 3 weeks. This chemotherapy is not commonly combined with other targeted therapies. There has been a large study that tested the role of Avastin, an angiogenesis inhibitor ("blood vessel blocker"), in mesothelioma and showed that it does not improve outcomes. It is not used in combination with chemotherapy. Nor are targeted therapies like FGF or FAK inhibitors, which are novel therapies that really haven't demonstrated any clear benefit in cancer at this time. While it would be reasonable to consider them in a clinical trial, they have no role in standard treatment.

The idea of hyperthermic chemotherapy is done in a few centers in the US -- I presume also some others in the world. The few places that do it think it helps, but this treatment is very toxic and is very far from being a standard of care.

Mesothelioma is a setting in which there is relatively little research because it's a very uncommon cancer, and much of what drives treatment is the sometimes very strong opinions of the doctors treating it and the misguided presumption by some doctors and many patients that it must be better to give the most phenomenally aggressive treatment a patient can survive. I would be very cautious about following the zealous opinions of people who are making judgments based on presumptions and faith rather than evidence. What often happens is that the healthiest patients with the lowest cancer burden with the most favorable cancer biology are selected for the most extreme treatments. If they do well, it is attributed to the treatment, even though they were exactly the patients expected to do best anyway.

(cont)

With regard to mistletoe, the short answer is that there is no evidence of any quality to suggest that it should be included in the treatment plan. That treatments are done somewhere is very different from them being useful. People do all sorts of things. I would say that neither I nor any other recognized thoracic oncology expert has ever recommended mistletoe injections for their patients. It wouldn't crack my top 500 recommendations for patients.

-Dr. West

I think that's a fair assessment of mistletoe for cancer. There isn't enough research to say much either way. There's always a potential danger, just as there is always a potential benefit, when interventions haven't been assessed enough to say more, but otherwise I'd say the leading risk is simply false hope that it's going to have a major effect. Perhaps, but I wouldn't presume that.

Good luck.

-Dr. West

Studies are too small to rely on data here. These aren't randomized trials: they are small numbers of patients, usually carefully selected, getting treated at only a few centers. I don't think it's really possible to generalize a broader experience without a randomized trial in which half of the patients get trimodality therapy and half of the patients receive a different, less aggressive approach. Another approach that is gaining traction among some experts is the so-called "Toronto approach" (developed in Toronto, also called SMART therapy, an acronym I can't remember the origin of the acronym for) in which patients receive 5 days of high dose radiation to the entire half-chest with the mesothelioma. followed immediately by an extrapleural pneumonectomy, followed by follow-up and no planned chemotherapy unless or until the cancer recurs.

I'll say that one approach that I still think is very reasonable in an an asymptomatic (no symptoms) patient with a small volume of mesothelioma is to follow it without treatment, until clear progression, if a patient can psychologically deal with that. Mesothelioma can sometimes develop over yers, sometimes over MANY years, and I'm very unconvinced that the long-term survivors of super-aggressive approaches to mesothelioma aren't just the same people who would have been alive ANYWAY 3-5 or even 10 years later if their mesothelioma had been left untreated or treated just with chemotherapy. To some surgeons, suggesting as much is sacrilege, but all of the approaches for potentially resectable mesothelioma are more based in faith and bias than actual evidence. I can assure you that I follow some patients with an indolent mesothelioma that shows barely perceptible change every 4-6 months on scans, whether I give chemo or not, and others respond well enough to chemo that I can treat them for years and years with minimal side effects.

It may not help to know of so many options, but there's much room for patient preference.

-Dr. West

Hi Mike, I've been out of www range for a few days and haven't had a chance to welcome you to Grace. I'm so sorry your brother is going through this. It sounds like Simon is lucky to have you in his corner.

It's true cancer mutates to grow through chemo drugs also each individual's system can only withstand so much of a drug. For both these reasons people with stage IV lung cancer are usually better off using only enough treatment to feel well as long as possible. A metaphor about living with non curable lung cancer is that of a foot race where treatment is a marathon as opposed to a sprint.

There are growing reasons today to look at current biopsies when so called targeted treatments are used such as those with an EGFR mutation have been using 1st gen drug like erlotinib then begin to progress (cancer mutates to grow through treatment). Doctors have found specific mutations that happen and have found drugs that work around the new mutation. But this is a specific only to those cases in which people have an EGFR, ALK, ROS1 mutation. For the rest/most people scanning is still the best way to watch what's happening. There's not information found in a biopsy that can alter treatment decisions. If there is reason to doubt a spot found on scan may or may not be cancer a biopsy may be in order.

I hope this is helpful. Best of luck to you and your brother. I hope he does well for a long long time to come.

Janine

While looking for info on “Toronto approach” I came across this,though not any new info, http://www.mesothelioma.com/blog/authors/jack/trimodality-therapy-for-m…

Hi Mike,

I just to add some thoughts to the good information Janine provided. Although it is true that for the most part a particular chemo drug eventually becomes ineffective, there are patients who remain on a single drug (especially in the case of targeted therapies) for an extended period. Patients are monitored with scans and if progression is seen, the recent trend (as Janine pointed out) is to re-biopsy to see if there is a new mutation for which a targeting drug has been developed.

If there is no progression, usually doctors will not re-biopsy, preferring to re-scan and perform clinical examinations of the patient. One reason is that biopsies are invasive procedures which are not risk-free, so they are only done when they will directly affect the management of the cancer. If you biopsy when there is no progression, you may discover a new mutation but if it's not causing trouble it would be premature to initiate treatment. If progression later appears, you would probably still need a new biopsy to be assured that it is the same mutation which is causing the progression so that the proper treatment can be selected.

JimC
Forum moderator

Not much to add. Scans (and symptoms) are definitely the way we monitor the pace of the disease, which almost invariably tends to accelerate over time, though sometimes that's just from "extremely indolent" to "still pretty indolent, but less so" over many years (admittedly, the best case scenario).

I couldn't say where the Toronto approach is being done. The surgeon discussing surgery options would be in the best position to speak to this, but I don't want to imply that this is the clear standard of care right now or that I am definitely advocating it as a best opion. Rather, it's the latest development that has captured the attention of the surgeons at my center who see a significant number of patients with mesothelioma.

-Dr. West

Hi Mike,

Targeted therapies such as those described in your quote have been the focus of much research for several years. As a result, it has become standard practice to test the cancer cells for certain mutations for which targeted drugs have been developed. These mutations occur most often in non-smokers, but they do occur less frequently in smokers, so more oncologists are beginning to test all of their patients.

If you search this site for "targeted therapies" or "EGFR" you will find a wealth of information. You may want to begin with Dr. Pennell's very thorough overview here.

JimC
Forum moderator

I think the bigger point is that while we're extremely aware of the potential importance of mutations in many cancers, though this hasn't been relevant yet in malignant pleural mesothelioma. This isn't to say that such mutations/targets couldn't be helpful for mesothelioma, but they haven't been shown to be useful yet in that setting.

-Dr. West

Sorry, we don't keep up with the reports coming out of every meeting around the world. I don't think this conference in South Africa is very likely to have changed global standards. The important trials are presented at just 1 or 2 main meetings, primarily ASCO (American) and ESMO (European).

I can't answer the question of the order of SMART protocol. That's what they did. Bear in mind that the "doubling of three year survival" is not a randomized trial of patients getting one approach or another, but a comparison of results of an earlier cohort of patients compared with a later cohort of patients in a single institution. This is not the same as a definitive test of the utility of one approach compared head to head with another.

There are always new things being worked on, but we can't address every new agent or trial being looked our around the world.

-Dr. West

I haven't seen any clinical research results with amatuximab, so I have no opinion of it. It's a theoretically appealing focus of research, but I don't know that I would recommend a patient get on a plane to pursue it.

-Dr. West

This is not clinical research. In my opinion it is of no clinical relevance. I think it is a mistake to chase down every publication on the planet about mesothelioma to try to cobble together an untested plan based on no clinical evidence.

-Dr. West

Mike,

I've asked a doctor who specializes in mesothelioma to comment. I hope your brother does well with whatever path he follows.

All best,
Janine

Mike,

I can't point you to any such graphs, but I would caution that if you find such information it is not very helpful to compare data from a trial of one treatment approach to data from another trial of a different approach. Unless the results come from the same cohort of patients randomized to one of the two approaches, the comparison can be misleading.

If you have not seen them, there are some discussions of trimodality therapy here on GRACE: http://cancergrace.org/lung/tag/mesothelioma/

JimC
Forum moderator

Indeed, there's so much bias from patients and docs in terms of what they are inclined to do that there are no trials that randomize very fit patients with a minimal tumor burden to close observation vs. trimodality therapy. I can assure you that both options are very reasonable, and I suspect that many patients in this setting could actually do well for years before showing evidence of significant progression. Moreover, I also suspect that many of the patients who do well after trimodality therapy do well because they were good candidates for trimodality therapy (having the most favorable characteristics associated with doing well no matter what treatment is given or not), and not necessarily because of the trimodality therapy itself. I suspect we will never have the evidence to show one approach is better or not.

The best person to offer contacts to discuss EPP would be the surgeon who has done these before, or possibly connecting with a mesothelioma discussion group online. HOWEVER, I can assure you that the experience leads to such variable outcomes that someone else's expereince may not be very generalizable for another person. It is an enormously big undertaking, and some patients do well, but others have quite significant pain and potentially shortness of breath afterward. Someone else's experience can tell how someone else has done, but there is no "average" or typical outcome after trimodality therapy and EPP.

-Dr. West

Nike, I hope your brother is feeling alright. Our faculty doctors can only recite what is known then explain the pros and cons of reading stats and I think Dr. West and Jim have done a good job at the latter. I looked around online and found the http://www.asbestos.com/mesothelioma/life-expectancy.php to have a lot of data such as life expectancy.

I imagine you have read these but just in case and for others here's a list, http://cancergrace.org/lung/tag/mesothelioma/
too and I don't recall you discussing Bevacizumab and VEGF which is discussed toward the bottom of the piece under<span style="text-decoration:underline;"> List of novel agents under investigation</span>: in this blog post, http://cancergrace.org/lung/2010/06/05/comprehensive-review-of-mesothel…
Bevacizumab aka Avastin is sometimes paired up with other chemo agents.

I hope there's something here of some help.

All best,
Janine

I don't think I have anything to add to Janine's summary and recommended links. I would make a couple of cautionary points.

1) There aren't necessarily published or easily findable stats for every endpoint. You may need to go to the actual reference and look at graphs to try to find numbers at various time points. HOWEVER, follow-up for the study is not likely go out beyond 3 years, so there aren't likely to be accurate numbers for long-term survival.

2) Stats are very good for populations but poor for individuals. Though we might be able to say that there's a 50% survival with cisplatin/pemetrexed at one year, every individual patient is either a 100% survivor at 1 year or not. There are some long term survivors out 3+ years; it's worth knowing that there are outliers as a proof of principle, at least.

Good luck.

-Dr. West

I'm glad to hear Simon is doing well for a man of nearly 59. I say that sarcastically because my husband is 59 and I'm not far behind. My husband too bought a new, to him motorcycle a about 3 years ago. BTW he has enjoyed that mc so much. He bought it with the money he got from selling a 76 hd mc that he no longer could man handle on the road. I hope your brother enjoys life from here out.

Janine

Hi Mike,

I would love to hear an update on how your brother is doing?

My mum was recently diagnosed with Pleural Mesothelioma and has started Chemotherapy however we are also looking in to the option of Surgery.

We live in Sydney, Australia.

Thanks
Giulia

<span style="text-align:center;">Mesothelioma Treatment Options</span>
<span style="text-align:justify;">
Mesothelioma treatment is decided by the stage of cancer and the degree to which it has spread. For early stage cancers which are contained in the thorax can be totally or partially removed by surgical procedures such as thoracotomy, lobectomy, pleurectomy and extrapulmonary pneumonectomy.

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This may potentially reduce the recurrence rates although overall survival is not affected. Some surgical procedures such as pleurectomy and pleurodesis can be used as a palliative option where indicated when the patient is not fit enough to undergo major procedures when “cancer” has spread to distant sites.

Mesothelioma treatment is aggressive cancer which develops from the mesothelium found in the lungs (pleura), heart and abdomen. Currently, there is no cure for this cancer but treatment is available to improve the prognosis and quality of life. The standard treatment mainly consists of surgery, chemotherapy, and radiotherapy. Some patients may also seek alternative therapy and experimental clinical trials. In most instances, a combination of these therapies with a multimodal approach is being used.....</span>
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Mesothelioma Treatment Options</b> </span>