Mixed Response after first line treatment in Stage IV NSCLC - 1252767

jmark
Posts:7

My 71yo dad was diagnosed with Stage IV adenocarcinoma NSCLC with bone (sternum, minimal uptake in spine, hip, rib and shoulder) and left adrenal gland mets on PET scan 10/12. Biopsy by bronchoscopy tested negative for EGFR and ALK. Began treatment with carbo, alimta, avastin every 3 weeks for 4 rounds. Also has had 3 rounds of zometa on 4 wk cycle. PET scan on 1/17/13 reveals significant progression of bone metastases (sternum, significant uptake in spine, rib, shoulder, hip, arm, leg) and left and right adrenal gland but shows significant improvement to primary lung tumor and mediastinal nodes (including resolution of post-obstructive atelectasis and mild pleural effusion). CT scan on chest 12/26/12 consistent with PET scan this week. MRI to brain has been clear prior to treatment and after 3 rounds. MRI on spine 1/11/13 consistent with PET scan this week. He is a 16 yr survivor of Stage 1B colon cancer with right side colectomy. His dr believes it to be primary lung but has not confirmed archival tissue samples from colon. He quit smoking 33 yrs ago and has been an avid runner and hiker for many years and generally in excellent health up until his diagnosis. What options are available considering this mixed response?

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Reply # - January 18, 2013, 09:25 PM

Dr West
Posts: 4735

I just did a couple of videos talking about how we might approach a mixed response:

http://cancergrace.org/lung/2013/01/01/mixed-response-video/

and also the biology behind a mixed response:

http://cancergrace.org/lung/2013/01/07/biology-of-mixed-response/

If the balance is more in favor of moving to something else, then it makes sense to primarily focus on the treatments we'd approach for progression after first line for advanced NSCLC:

http://cancergrace.org/lung/2010/10/04/lung-cancer-faq-2nd-line-nsclc-o…

Good luck.

-Dr. West

Reply # - January 19, 2013, 08:03 AM

jmark
Posts: 7

Thank you, Dr. West. This site has been very helpful for information and understanding. In reviewing the links above and others on this site, would there be value added to consideration of treatment choices with a biopsy of the bone cancer and/or chemosensitivity testing prior to second line treatment? From my basic understanding, efficacy of treatment may translate to minimal OS extension and does not ensure quality of life. Does the site have any links addressing alternative approaches to maximize quality of life?

On a different note, his CEA was 0.1 on 3/11. His CEA was 52 on 10/12. CEA rose to 70 on 11/12. CEA continued to rise to 96 on 1/13. Treatment began 10/12. I have also read the site's links on tumor markers and understand this number may or may not be helpful. Positive immunostains from lung biopsy were CK7 and CDX2. Negative were CK20, TTF-1 and Napsin A in addition to EGFR and ALK. Are you aware of any clinical trials available that fit his profile?

Reply # - January 19, 2013, 11:54 AM

Dr West
Posts: 4735

I'm not sure exactly what you mean, but I think the answer is no. I would also say that very few, if any, expert lung cancer specialists put any stock in chemosensitivity testing that is marketed aggressively, but it doesn't include any evidence that people who do it live any longer than people who don't. Many tests are also quite hard to do on bone biopsies, which require harsh chemical treatments to decalcify the bone.

-Dr. West

Reply # - January 20, 2013, 10:12 AM

catdander
Posts:

This would be a marvelous advance in the treatment of nsclc or any cancer but it appears from your link that it's still in the early stages or clinical research. A bewildering number of promising treatments go into phase 2 clinical trials that don't go on to prove to be beneficial to people with cancer. The trial you mention had good results but seems to have had only 30 people in the trial. So I don't know how positive anyone can be with data from such a small group...other than move forward with more testing.

We'd all appreciate the treatment advances sooner than later but it's inspiring to know that our dedicated researchers are plugging away.

I hope this goes on to be more compelling than initial such tests.

Reply # - January 20, 2013, 11:03 AM

Dr West
Posts: 4735

I think Dr. Nagourney is a truly committed scientist, and I agree that it is promising. He also used wording that speaks of the potential of this work if it is validated in a larger setting. It is phase II research in one smallish patient group, which is subject to a very real risk of selection bias, as we have seen here over and over and over. If it is tested in a randomized trial that demonstrates that patients who undergo the chemo selection process based on their lab investigation do significantly better than patients who are managed in the best way we know how now (but not including the Rational Therapeutics protocol), I think it will be a real step forward. But these claims have been made for years and years and years, and we still have yet to see a prospective, randomized trial show that patients who undergo this kind of testing do significantly better. Meanwhile, the tests are marketed and often promoted by industry, patients, and caregivers who are selling a concept more than compelling evidence.

-Dr. West

Reply # - January 20, 2013, 11:16 AM

dr. weiss
Posts: 206

There are different levels of evidence behind different markers trying to predict the efficacy and safety of lung cancer drugs. Here's my opinion (note word choice) on our current state of affairs:

BEST EVIDENCE:
*EGFR mutation- People with mutation have high probability of response to tarceva
*ALK rearrangement- People with rearrangment have high probability of response to crizotinib
*Non-squamous histology- People with nonsquamous NSCLC have better responses to pemetrexed than SqCC
*Non-squamous histology- Avastin is safer in people with nonsquamous NSCLC

VERY PROMISING:
*ROS1- People with rearrangment have high probability of response to crizotinib

PROMISING:
*ALK rearrangement- High probability of response to HSP-90 inhibitors.
*KRAS- Perhaps high probability of response to HPS-90 inhibitors and MEK inhibitors.
*MET- Overexpression may predict for efficacy of metmab.
*Squamous histology- Patients with squamous histology may have superior response rates to abraxane, but not superior survival
*Elderly- Elderly patients may have superior survival with abraxane

MAYBE:
*BRAF- Mutation may predict for efficacy of BRAF inhibitors
*ERCC1- Proposed marker for platinum sensitivity
*RRM1- Proposed markert for gemcitabine sensitivyt
*TS- Proposed marker for pemetrexed sensitivity

DATA UNIMPRESSIVE THUS FAR:
*A variety of expensive assays claiming to predict which chemo will work.

With a terrible cancer like lung cancer, it is natural to want to shoot for better results than those found with standard chemotherapy. I agree with this feeling--I've dedicated my life to lung cancer research out of a dissatisfaction with our current standards. But, in my opinion, we should look to data to say which things are most promising. And, when new unproven therapies are tried, we should keep track of the results so that we can learn what really works. To me, this means clinical trials.

Reply # - January 20, 2013, 01:02 PM

jmark
Posts: 7

Thank you so much for your time and dedication. It continues to be a journey. We meet with his oncologist this week and will hopefully get a second opinion as well on the latest information. My concern is that the bone mets continue disease progression while we continue to treat the primary NSCLC (which positively responded to first line treatment). The bone mets cause severe pain and significantly impact his quality of life. His oncologist has recommended halting treatment for radiation to the specific bones causing pain (spine and sternum) but says it is palliative only. And he isn't ready to settle for palliative only at this point. From my research, the only other bone mets treatment option (besides Zometa) is Xgeva. Are there any other bone mets targeted treatment available to slow disease progression in the bones? Best of luck to you both in your continued research to conquer this horrendous cancer. God bless.

Reply # - January 20, 2013, 01:39 PM

Dr West
Posts: 4735

The treatments we have for bone involvement are really the chemo or other systemic anticancer treatment (like a targeted therapy of Tarceva, for instance), the Zometa (zoledronic acid) or XGEVA (denosumab) you mentioned, and radiation to treat the pain of a painful metastasis and reduce the structural instability in a bone metastasis at risk of fracturing. Occasionally a surgery is done to stabilize a bone, but that really rounds out the list of what there is.

There are a couple of ways that the term "palliative" is used. One is just "non-curative", and really by definition, nearly all treatment of metastatic lung cancer is palliative. The goal is often to prolong survival, sometimes by a lot, but we can't offer the promise of a curative intervention. The second definition means "to reduce symptoms and maximize quality of life", but that is just in addition to whatever else we might do. It's not a consolation prize that is code for "ineffective token therapy".

-Jack

Reply # - February 7, 2013, 02:09 PM

jmark
Posts: 7

Just wanted to update. My dad started second line treatment of Taxotere and Avastin last week. We followed up with his onc yesterday and his cts had dropped very low. He was extremely short of breath. In addition, he was in so much pain that he was barely ambulatory despite taking Oxycontin 20mg twice a day. She admitted him to the hospital for MRI on spine, CT on chest, and XRAYs on other bone met areas of concern as well as blood boosters and saline. We are meeting with a radiation oncologist tomorrow. MRI showed a 5cm lesion on his spine and 1cm lesion on his hip. CT scan shows stable from previous scan. My dad thinks the radiation oncologist implied that he would receive radiation on targeted areas and then resume chemo. But we understood from his oncologist that the two were mutually exclusive and that we would not continue on chemo once we started radiation. Can you offer any clarification?

Reply # - February 7, 2013, 08:44 PM

Dr West
Posts: 4735

Chemo is typically suspended during the radiation in this setting, and it may be interpreted that the chemotherapy used up to now is not effective because the new lesions are evidence of progression on this treatment. So it would be typical to consider subsequent, often different, chemotherapy or other systemic therapy following completion of the palliative radiation.

Good luck.

-Dr. West

Reply # - March 2, 2013, 03:29 PM

craig
Posts: 330

jmark,

Given an interest in experimental trials, if he is still fit enough for one, you might be interested in determining the driving mutation of the lung cancer. Occasionally a trial for useful one looks promising (though more often not).

Since there is a history of smoking years ago and you've already tested EGFR and ALK, you'd probably test next for the not-so-useful-yet KRAS (very common in smokers, uncommon in never-smokers).

If KRAS is the one, there are some clinical trials for that. Not many too promising yet, but there might be a couple okay ones and we'll probably hear more about them in June (big ASCO conference). (In the meanwhile, I think a recent trial suggested selumetinib added to chemo might improve response a bit.)

If triple-negative for KRAS, EGFR, and ALK, there's still a chance it could be driven by a rarer one. The odds of something useful aren't high, but might worth a shot. Ask your oncologist.

ROS1 is the one I have, with good results for me for 1-1/3 years so far. ROS1 is mostly in younger never-smokers, but there are exceptions -- some early data found 10% of ROS1 in smokers, and found ROS1 even in a 70-something patient. So the odds for this very rare one would be small, but maybe worth a shot.

RET is another potentially promising one, but I have yet to see any research results on it. RET, too, is more common in younger never-smokers, probably with exceptions, too. (RET trials borrow drugs for RET-driven thyroid cancer.)

There's also MET and HER2 and BRAF, though I'm not sure how well those trials are doing.

And if the driving mutation isn't a useful one, for when chemo options stop being useful you might ask your oncologist about any other "promising" trials. (Be sure to discuss travel preferences or limitations -- the best trials usually aren't local.) BTW, I'd always ask for the odds of shrinkage or stability from a trial drug, & how long.

Best hopes,

Craig in PA

Reply # - March 13, 2013, 08:10 PM

jmark
Posts: 7

Latest update on my dad. During the third week of first cycle of the second line treatment Taxotere, we saw a radiation oncologist. My dad received radiation to the spine and the hip for four consecutive days that week. The oncologist convinced Dad to stay the course for one more round and complete the second cycle of Taxotere despite his reluctance and then do a scan to test for efficacy. She helped to manage the side effects better by giving him a Neulasta shot 48 hrs after the chemo. His oncologist also decided to eliminate the Avastin on this treatment. His counts dropped but not like last time. His pain in the sternum bone lesion did flare up last week such that he went back to his radiation oncologist for one day treatment to the sternum. He has upped his pain meds to 40mg Oxycontin twice daily with 1 or 2 break out pills. He saw his oncologist last week and expressed concern that his body and pain were telling him that the Taxotere was not working. Amazingly, shortly after that doctor visit, his mental outlook went from a horrible place to actually wanting to live. He couldn't explain what happened but thanked God for the change of heart. Six days after this mental breakthrough, he went for his PET scan on Monday. We got the results yesterday and the report showed significant improvement. It showed decreased SUV values in all bone lesions except the sternum. No new bone lesions were found. It showed decreased SUV values on both adrenal glands. And miraculously, showed no residual hypermetabolic mediastinal lymphadenopathy. And showed no abnormal pulmonary uptake. The results left no doubts that the Taxotere is working at the present time. His red count is still low today so he will get a shot of Procrit tomorrow. But he agreed to move ahead and have his third treatment of Taxotere today and stay the course. I wanted to share the feedback of positive response to second line drug after mixed response to first line treatment.

Reply # - March 13, 2013, 09:39 PM

Dr West
Posts: 4735

That's really great to hear. It's wonderful he's responding well and has had a turnaround in his outlook.

Just so you know, Procrit is associated with a modestly reduced survival, so it has become a lot less commonly recommended in recent years, as evidence has mounted that in cancer patients, it can have a detrimental effect on survival. I suspect the oncologist reviewed this, since it's part of a rather elaborate consent process for Procrit nowadays.

-Dr. West

Reply # - March 21, 2013, 11:16 AM

jmark
Posts: 7

Today is Day 8 after my dad's third treatment of Taxotere. His red blood count remained low and his oncologist felt Procrit was needed. He received that shot and two bags of saline earlier this week. For the past 2 days, he has been experiencing slurred speech and severe "fogginess". We called the oncologist and they want to see him. He absolutely hates brain MRIs. And both previous brain MRI's have been clear. Are there any options other than MRI to find out the cause of these symptoms? Are these typical side effects to chemo known as "chemo brain"?

Reply # - March 21, 2013, 12:47 PM

JimC
Posts: 2753

Here's what Dr. West has said previously regarding chemo brain vs. brain met symptoms:

"there's a huge amount we still don't know about chemo brain. Here's an article from the NY Times this week that asks whether the suspected side effects of chemo are actually more attributable to the underlying cancer:

http://www.nytimes.com/2010/10/12/health/research/12mental.html?_r=1&re…

One thing I'd add that may be reassuring is that subtle (or not that subtle) memory problems and word-finding aren't as typical of brain metastases as symptoms like balance problems/falling, vision changes, headaches, nausea/vomiting, and seizures."

I hope these symptoms are a temporary effect and clear up soon.

JimC
Forum moderator

Reply # - March 21, 2013, 06:40 PM

Dr West
Posts: 4735

Chemo brain is really more subtle than that...not really slurred speech but problems keeping track of plans, making associations with words, etc.

Sometimes metabolic issues can be a culprit, which might be detected with a blood test looking for salt imbalances or other problems that might be readily reversible.

Alternatively, a CT of the brain isn't quite as detailed as a head MRI but would still be a fine way to screen for a brain lesion that isn't extremely subtle. It's still a fine test and is a lot less to go through for people averse to an MRI.

Good luck.

-Dr. West

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