My 60-year old non-smoker East Asian mother in law was diagnosed with Stage 4 Lung Cancer about 3 three week ago. The cancer was identified as poorly differentiated adenocarcinoma that has spread to the pleural fluid. Biopsy of a pleural lesion revealed,
"Sections show multiple pieces of core fibromuscular tissue. No lung parenchymal tissue identified (or remained detectable). There are areas of desmoplastic stroma with invasive solid sheet proliferation of neoplastic cells with moderately pleomorphic nuclei and occasional tumor cells with pale mucinous cytoplasm. No gland formation is seen. "
A cobas EGFR test revealed she is EGFR negative. (I understand this can happen more frequently with mucinious cytoplasm.) A CT scan showed enlarged lymph nodes (right hilar and subcranial) although the cancer appears to be merely in in the right lobe (heart/aorta/pulmonary artery appear normal). Her symptoms consist of an occasional cough. She seems to be in good health, weighing about 100lbs.
After the negative EGFR test we heard about NCT01639001: "A Study Of Crizotinib Versus Chemotherapy In Previously Untreated ALK Positive East Asian Non-Small Cell Lung Cancer Patients".
The problem we have is that to participate in the study a portion of the biopsy cells will have to be mailed to the USA and we will know the results "in two weeks" during which we cannot begin chemotherapy.
What are the risks of delaying treatment 2 weeks? If it comes back ALK+ -- treatment cannot start until about 1 week after the results are received.
I am looking for any information to help me evaluate the obvious question: "Are the potential benefits of a targeted treatment worth the delay?" Based on CAP guidelines I suspect so. But I am not a medical doctor and the probability of being ALK+ is lower. She is eager to start treatment -- which may decide the question despite any medical advice.
Thank you for your help,
aschweig
edit2: Onco suspects small-cell LC / meso.
kg->
Reply # - August 16, 2013, 09:57 AM
Reply To: Wait treatment for a chance to participate in study of
Hello aschweig, I'm very sorry your mother in law has been diagnosed with lung cancer. I take it from the trial you're talking about that she is in China. And I'll assume crizotinib isn't given outside trials there? I hope it will be soon.
Often people in good shape will wait to have mutations tests read before starting treatment. There is a very good discussion on the subject that I've pasted a link to below.
"Crizotinib (PF-02341066) is a new compound that inhibits the eml4/alk fusion product. While it is still available only in trials, the preliminary data is so good that I believe that any patient with a known translocation should be enrolled on one of these trials, if at all possible, for first line treatment." http://cancergrace.org/lung/2010/04/16/introduction-to-first-line-thera…
Note the phrase, "if at all possible" includes how comfortable a person is waiting for test results vs starting treatment. But if this is her only chance to get crizotinib and she is positive then she may change her mind.
Note too the blog was written before it criz was approved in the US and Europe. I hope it is available soon where you are.
The bottom line is it depends, how comfortable your mother in law is with waiting on treatment, how physically able to go without treatment, and if she does have sclc the cancer usually moves much faster and would need to start treatment. She and her doctors are the only people to balance these pieces and answer the question.
You are right in wanting the most info from which to help her make these difficult decisions. Know that a breather/a sigh of relief is coming for everyone after the decisions are made.
Don't hesitate to ask any follow up questions for our doctors.
Janine
forum moderator
Reply # - August 16, 2013, 10:55 AM
Reply To: Wait treatment for a chance to participate in study of
Hi -- Thanks for the email. She's in Thailand. We will try to get both an ALK test and any other requested tests from our Onco (actually currently interviewing several at the largest hospitals.) As I understand, the trial is the only way to (possibly) get Crizotinib currently.
We were somewhat shocked to learn today (after I wrote my post) that our Onco wanted additional tests regarding SCLC/Meso (why didn't the pathologists who looked at the pleural fluid and biopsy mention this originally -- but both did mention adenocarcinoma??)
I am curious: are there current "approved" immunotherapy approaches for stage 4 lung cancer? From my naive point of view, approaches like inter-pleural administration of IL-2 seem like obvious treatment modalities.
Reply # - August 16, 2013, 05:56 PM
Reply To: Wait treatment for a chance to participate in study of
There isn't actually any evidence that giving a targeted therapy immediately is better than giving the same treatment in second line or later, as long as a person is still doing well after first line. While we generally favor doing targeted therapies earlier rather than later, the main benefit is to ensure that people have a chance to get the most effective therapy for their cancer, which is never more likely than giving it first line. But most people, at least those who aren't frail and don't have the most fast-growing cancer, will still be fit enough to receive the targeted therapy and do very well. So it's very reasonable to start first line therapy and then jump in with targeted therapy later, if a mutation happens to be found.
There are no approved immunotherapies for lung cancer, or stage IV NSCLC in particular. However, IL-2 is a staggeringly toxic treatment that has never been shown to improve outcomes in lung cancer, so I must confess that I wouldn't be REMOTELY tempted to do intrapleural IL-2 therapy without extensive research first, since it may be more effective as a form of torture than a form of lung cancer therapy.
-Dr. West
Reply # - August 16, 2013, 06:54 PM
Reply To: Wait treatment for a chance to participate in study of
Hi Dr. West --
My understanding was that local administration of IL-2 avoids the systemic toxicity while achieving potentially higher concentrations of interleukin in the targeted cancer. One study by Castagneto suggests IL-2 administration could be used to stop many pleural effusions. Granted: IL-2 does not match the nearly guaranteed effectiveness of pleurodesis -- but my understanding is that pleurodesis isn't exactly a walk in the park. And IL-2 offers (a perhaps remote) possibility of stimulating a longer-lasting immune response to the underlying cause.
I think the 2008 paper by Otter et al reviews available evidence -- although the authors stress intratomoral application is preferred to peritumoral or "inhalational" or other approaches.
Perhaps something about lung cancer (as opposed to melanoma or renal cancer) makes it less susceptible to IL-2? Or perhaps, IL-2 is known to interfere with other first-line treatments for LC which have already demonstrated superior efficacy? So why mess with a good thing with an adjunctive therapy that might mess it up? Or perhaps IL-2 adds nothing at all, while taking up the doctor's time?
The above question are intended to be semi-rhetorical.
Thanks for the feedback!
Reply # - August 16, 2013, 09:45 PM
Reply To: Wait treatment for a chance to participate in study of
I appreciate your suggestion of references, which I'll need to check. I have never used locally administered IL-2 and have only cared for patients who received it as a systemic therapy, typically with astonishing toxicity. The bigger issue I have, though, with local therapies for advanced NSCLC (whether IL-2 or various others), is that this is a systemic disease, so giving a local therapy for a systemic disease really doesn't solve the problem. Once a lung cancer has emerged in the pleural fluid, it can also travel through the bloodstream to other locations. Though local therapies can certain be effective to palliate local symptoms, but none has proven to be effective in improving survival.
-Dr. West