progression on co-1686 with brain met - 1271564

Hi kkh,

I'm sorry your post sat so long but we're on it and it will be addressed and will be addressed by a doctor soon.

I hope your dad does well on the treatment plans decided on.

As for the mutations the tests have shown it is possible to look on clinicaltrials.gov for possible trials near you or get a 2nd opinion from a lung cancer specialist who conducts trials.

Best of luck,
Janine

I wouldn't say that it's an absolute mandate to to whole brain radiation, but I think it's a very reasonable suggestion when someone has a rapid progression within the brain. When someone has small cell lung cancer, which very frequently involves the brain and almost always causes multifocal disease, the rule is that whole brain radiation therapy (WBRT) is essentially always the right choice and that stereotactic radiation is the wrong answer. If there are many new lesions developing, it makes it very likely that there will be more again, right behind the ones getting treated. While I certainly understand the hesitation about WBRT, and we do recognize that there can be cognitive side effects, I think that the fear about it is often beyond the rational range, as if it's better to let the cancer progress unhindered by effective therapy than to give WBRT. It isn't.

There are some anecdotal cases of responses to AZD9291 (now known as osimertinib) after rociletinib, but the far more evidence-based approach is with chemotherapy. Immunotherapy is the hottests idea on the planet right now, but in fact, the evidence on immunotherapy for patients with EGFR mutations and perhaps other driver mutations suggests that it often isn't especially effective. It's important to remember that chemotherapy helps many patients, sometimes for a very long time. It's not just a pointless consolation prize just because it's last year's model. It has proven its efficacy in hundreds of thousands of patients, compared with anecdotal reports of a few stray patients who have responded to osimertinib after rociletinib.

Finally, I think it's very reasonable to do a biopsy to rule out small cell lung cancer, which is a documented phemonenon. It would be far more likely to produce a result that has a meaningful impact on the treatment plan than any of the other mutations identified on the molecular panel.

Good luck.

-Dr. West

HI KKH,

I am very sorry to hear of your diagnosis of LC. There have been claims made for the ability of various drugs to cross the blood-brain barrier, most of them anecdotal. The truth is that most drugs cross the barrier to a certain extent, but usually not in a sufficient concentration to be effective. That is the reason for pulsing Tarceva, to get an effective dose of the drug into the CNS, and some patients benefit from it. It's also the idea behind intrathecal chemo, but its track record in treating LC in lung cancer is not good, and as you point out it can be painful and cause a variety of side effects.

There isn't any scientific evidence regarding the use of paw paw in this context. GRACE's Dr. Bufi has posted his thoughts here on paw paw (graviola - annona muricata): http://cancergrace.org/alternative-medicine/2008/12/01/graviola/ The bottom line: "I would not take or recommend a graviola product or any graviola extract as a dietary supplement. We do not have any convincing proof of efficacy, dosage, concentration, purity, nor basic safety data on the graviola plant."

JimC
Forum moderator

Hi KKH,

If you're getting the PD-1 and PD-L1 testing, and T790M has already been detected, there isn't much else to be tested outside of a trial that is targeted a specific mutation. Comprehensive mutation testing, which can reveal many different types of mutations, is an interesting concept, but most of the mutations detected have no therapies in existence to target those mutations. You've gained information, but it's not really usable.

CSRAs [chemotherapy sensitivity and resistance assays] seek to determine which chemotherapy agent would work best for a patient, but their accuracy is highly suspect. As Dr. West has said:

“I think that this work is very interesting, but companies professing to be able to predict what treatments will work have been promoting these services for well over a decade, yet they are not considered a standard approach yet. Why? Because there are major differences between an isolated collection of tumor cells in the lab and the actual biological condition of the cancer in a living patient, which can be far more heterogeneous, depends on blood supply to the cancer, metabolism of the treatment, and has an ongoing ability to divide and generate new mutations. But most importantly, there is no prospective study of multiple patients that has ever been conducted by a company that offers sensitivity testing that has ever been shown to improve outcomes for patients with lung cancer.” – http://cancergrace.org/forums/index.php/topic,1173.msg6153.html#msg6153

[continued in the next post]

[continued]

And as Dr. Weiss points out:

“An assay that does not work could potentially harm patients. Let’s say, for example, that the assay predicts resistance that is not present to what our current studies suggest is the best drug in a given situation. If I then use a different drug, I have harmed my patient. Let’s be clear hear–we all have the same goals of improving care. We just have different opinions about how to get there.” – http://cancergrace.org/forums/index.php/topic,3082.msg31972.html#msg319… ‘
from http://cancergrace.org/forums/index.php?topic=9415.0

Pulsed Tarceva has been used in large part because Tarceva tends to be fairly well-tolerated, while it is difficult to give higher doses of most other drugs; the side effects would be unmanageable. So even if higher doses of other drugs might produce higher, more effective concentrations in the CNS, it's not an attractive option.

How long to continue pulsed Tarceva would likely be a function of what is happening with LC symptoms. If after starting therapy they continue to escalate, then you would probably not give the therapy very much time, as Tarceva is often effective fairly quickly when there is an EGFR mutation. If symptoms improve, pulsing would probably continue as long as it is effective and tolerable.

Tarceva really won't target T790M, as that mutation confers resistance to it. But it is possible that the lower concentrations of Tarceva that have reached the CNS have not caused T790M there, so the cancer cells in the CNS may not have developed resistance.

Since the choices for treating LC in lung cancer are limited, the trial you cite sounds as though it could be a good option, especially if pulsed Tarceva proves ineffective.

JimC
Forum moderator

From reading the conclusions on your link it states melatonin may affect the sensitivity of radiation. If it's not part of the radiation oncologist's treatment plan it could over sensitize the area treated. "...due to its antitumor and radiosensitizing properties, treatment with melatonin is likely to increase damage to the tumor".
The biggest take home is,
"based on the discussions presented earlier, we conclude that melatonin may be efficient in improving the therapeutic gain in future radiation oncology treatments. However, further experiments and clinical trials on this subject are still necessary to fully validate it."

As more often than not treatments hoped to improve longevity and or quality of life in people with cancer end up not and sometimes even making matters worse. So jumping the gun on therapies before they are fully vetted can be quite dangerous.

Perhaps speak with the radiation oncologist about this issue and take along the article you've linked here.

All best,
Janine

In this situation, I think it would be ideal to do carboplatin + Alimta after finishing WBXRT. As Dr West says, it is not just a consolation prize. If anything, chemotherapies tend to be particularly effective in EGFR mutant lung cancer. As you mention above, Alimta does have fair blood-brain penetration.

If instead your dad is simply too sick for any chemotherapy after WBXRT, then trying the commercial Tagrisso seems like a good "Hail Mary" option to try.

There is also an EGFR inhibitor called AZD3759 which has almost 100% blood-brain penetration, however this is still in early clinical trials. Hopefully this drug can be used in the future, but it is not commercially available any time soon. I have a link to the trial below.

http://meetinglibrary.asco.org/content/146873-156
http://www.ncbi.nlm.nih.gov/pubmed/26313252

https://www.clinicaltrials.gov/ct2/show/NCT02228369

Hi kkh130,

It is common to hold Avastin both before and after an invasive procedure. Dr. West has said "Because avastin can interfere with wound healing, I don't restart it on someone after a surgery or dental work for at least a week or two." - http://cancergrace.org/forums/index.php?topic=530.msg2746#msg2746

He has also said "We generally favor waiting at least 2 or 3 half-lives, or about 6-9 weeks, after stopping Avastin (bevacizumab), to really significantly reduce the risk of bleeding/wound healing process." - http://cancergrace.org/topic/hip-replacement-surgery-while-on-chemo-for…

So it's not uncommon to have a break of 8-10 weeks from Avastin, usually without any problem. In your dad's case, he's still receiving carboplatin and Alimta, which are likely doing most of the heavy lifting in terms of treating his cancer. The value of adding Avastin is not entirely clear, although it is frequently done.

There are many different Tarceva pulsing regimens in use, and there is no real standard. Toxicity varies so much from patient to patient that it is impossible to predict how one particular patient will do. Tarceva has a half-life of 36 hours, so spreading the pulsed dose out over the course of the day won't make a big difference in how much is in his bloodstream at any given time. In addition, since Tarceva should not be taken close to the time a patient eats, taking it more than once a day causes dose scheduling/meal complications.

JimC
Forum moderator