Any Studies on Changing Chemo - 1254300

Hello koal, It's true that most 1st line chemo treatments consist of 4 to 6 cycles with a platinum doublet treatment. That is because platinum drugs have a great tendency to cause hypersensitivity after 6 treatments causing more harm than good. After first line though platinums are no longer used and single agent drugs are used until they stop working. Using one drug until it no long is effective is a long held standard in cancer treatment. It's not felt that moving around from one to another is making any of the treatments last longer. With stage IV you want to use drugs for as long as possible to get everything out of it you can. You'd never know how well one is working if you use it a couple of treatments then change, you wouldn't have a chance to measure results with scanning.

Here are links to discussions about treatments lines. Don't miss the further reading at the end of the posts, we have an extensive library. Our search engine is very good though you may need to log out before accessing it depending on your browser.
On first line platinum based treatment, http://cancergrace.org/lung/2010/09/18/lung-faq-ive-just-been-diagnosed…

On maintenance treatment, http://cancergrace.org/lung/2010/09/24/lung-cancer-faq-im-coming-to-the…

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

I hope this helps, please let us know of any follow up questions you will ;) have,
Janine

I just realized I didn't really answer your question. There is no data suggesting moving from one treatment to another is helpful. I don't really know if it's been studied due to the fact that most studies are performed to see if and how long a drug will work. Since scanning is the way efficacy is measured, changing drugs every few weeks wouldn't give the cancer and drug interaction time to show a difference.

But I'm just inferring. I'll ask a researcher to comment.

Janine
forum moderator

OK, I'm taking a deep breath, recognizing I may go over the 2k character limit (sorry Jack) and will take a trip down memory lane regarding both duration of therapy, and the question of switching drugs.

Regarding duration of therapy, there are two major trials that defined a standard of care of 4 cycles. Dr. Socinski compared 4 cycles of carbo/taxol vs. carbo/taxol given until progression. Survival was similar, but toxicity worse with carbo/taxol until progression. Park randomized patients who had no progressed after 2 cycles to 2 additional cycles (so 4 total) or 4 additional cycles (so 6 total); survival was similar. So, the standard of care for 1st line therapy is 4 cycles of carboplatin + a partner drug. I do very, very occassionally break this rule in my practice. For the patient who's scans after 4 cycles show signficant additional shrinkage cmopared to the scans done after 2 cycles and who have tolerate chemo incredibly well, I consider going to 6 cycles. In practice, I do this once or twice a year.

You asked about the potential value of switching drugs. I'm not aware of any positive trials switching drugs during the initial doublet (carboplatin + partener) period. However, the JMEN trial randomized patients who had not progressed after 4 cycles of (non-alimta containing) chemo to observation or maintenance alimta. The maintainence alimta did provide a survival advantage, driven by the non-squamous patients. The only other trial I'm aware of with a switch strategy is an older randomized phase II trial that I see as conceptually positive, but which we rarely talk about because it missed the statistical bar. Fidias randomized nonprogressing patients after 4 cycles of gem/carbo to 6 cycles of consolidation docetaxel or observation. The observation arm was to get docetaxel at the time of progression. Survival was better improved with docetaxel, but the p value missed at .085. (more to come...I'm out of allowed space)

(Cont)

What I found really interesting about this trial is that 40% of patients in the observation arm were too sick at the time their cancer progressed to actually get consolidation docetaxel. Did the benefit of consolidation docetaxel come principally from guaranteed exposure to another active drug? I think that it did--in the patients who were well enough to actually get docetaxel, survival was almost identical to that in the consolidation arm.

I've proposed a trial to try to revive the strategy that Fidias pioneered. My principals are that I'd like to extend survival (duh) with the lowest toxicity and patient inconvenience possible. My personal belief is that while a switch strategy could provide some benefit from prolonged duration therapy, the greater benefit is probably from guaranteed exposure to a second active drug with a different mechanism of action. Further, while patients want to maximize survival, many would prefer to hit the cancer hard, then be able to have a chemo-free period (in other words, consolidation with a fixed # of cycles instead of chemo for life). My problems with the Fidias study are that is was underpowered (so I'd like to power my study better) and that docetaxel is a bit toxic (so I've proposed it with a drug with less side effects). I'll keep you updated--so far, I'm very impressed with the level of dialogue and thinking from the company that's considering it and I'm really hoping to get to collaborate with them.

How exciting, Less chemo! Would you scan earlier and or use better symptom disclosure practices to know when to move back into treatment?

I don't think there are any trials showing any benefit to switching before someone has completed 4-6 cycles or demonstrated progression. In general, one principle worth considering is that we don't have such a long list of effective treatments for advanced lung cancer, especially if it has been previously treated, that it's typically wise to discard any before we need to.

I completely agree with the premise that the major benefit of maintenance therapy is that it assures that everyone most likely to benefit from further therapy (the people who didn't progress or experience prohibitive side effects after 4-6 cycles of first line therapy) actually receive additional treatment with an agent that has activity in previously treated patients with advanced NSCLC. But it's worth bearing in mind that the PARAMOUNT trial of continuation maintenance Alimta (pemetrexed) after 4 cycles of cisplatin/Alimta showed efficacy results every bit as good if not better than any "switch maintenance" strategy, which really argues strongly against the concept that changing treatments is clearly a better strategy.

Finally, with regard to the Fidias trial's shortcomings, which are several, I would point out that one issue is that to move on to "delayed Taxotere (docetaxel)" or "Taxotere at progression", patients had to show specific evidence of progression that could be higher than would be needed to lead many good oncologists to recommend restarting treatment (such as worsening symptoms or rather modest progression on scans that doesn't quite meet the criteria for official progression), and the interval until the subsequent scan after starting a break was 3 months. I think that's just too long, and I sincerely question whether if you redo a scan 6-8 weeks later, you wouldn't capture 90% or more of the patients and be able to give lots of people a well-needed break from treatment without losing anything.

-Dr. West

No. I'm saying that it's most typical to give 4-6 cycles of first line chemo and then consider a treatment break or either continue on an agent from the first line setting (typically NOT done with carbo/Taxol (paclitaxel) because people develop disabling neuropathy with ongoing Taxol) or switch maintenance with a new agent such as Alimta (pemetrexed) or Tarceva (erlotinib), though the data with Taxotere (docetaxel) would also arguably justify its consideration too (the trial with it only failed to show a statistically significant survival benefit because it was underpowered and designed better than the maintenance therapy trials that showed a survival benefit, which most clearly did NOT give the same access to subsequent effective therapy to the non-maintenance therapy patients).

A treatment break is still a very reasonable consideration in some patients.

-Dr. West

Dr. West. You bring up an interesting point re time between scans. My husband is on maintenance and his oncologist insists on at least 3 months or more between scans. He is planning on going off mantenance due to some side effects. I hope that the oncologist will go to 6 - 8 weeks between scans in this new situation, but I doubt it.

follansbee

My husband too is on a 3 month interval, even before the cancer was considered indolent. I trusted that symptoms would point us to a scan sooner rather than latter if the need arose. I know we've been very lucky all things considered.

Can I ask what type of scans he's getting follansbee? At first I had several discussions about CT vs PET scans with the oncologist. D's case of a pancoast tumor possibly resectable warranted a PET in the beginning but he continued with the practice and I wasn't going to argue over the point. (probably should for the nation's healthcare's health) Anyway insurance only pays for one every 3 months where as CTs can be ordered more regularly because that's the standard of practice.

He gets a CT with contrast. We ask occasionally if they could be done more frequesntly, but the oncologist doesn't see the need.

I have found that my points are better recieved with a copy of the resource in hand.

I would say that 3 months is a defensible but not optimal approach. I and many other lung cancer specialists think 3 months is too much time for change to occur in patients with advanced NSCLC (with the exception of people who have been doing very well for a long time, ~6 months or longer). Waiting 3 months to repeat a scan in someone at high risk for progression could mean that the person has convincing progression within 6-8 weeks and then continues to experience a decline for an extra 4-6 weeks unnecessarily when they could potentially be on a more effective therapy in that time.

-Dr. West

Thank you, Dr. West and Catdander. We'll take this information with us to his next office visit. Hopefuly, it will help our case for CT scans 6-8 weeks apart, at least while he's off maintenance. In the meantime, I'll search through this site and see if I can find any studies on frequency between scans.

follansbee

I don't think you'll find any studies here, because I don't know of any, so I would be surprised if I or one of the other faculty members wrote about that in the context of any data. You may well find other documentation that several experts also favor a shorter interval of follow-up, though.

-Dr. West

Thank you, Dr. West.

And Koal, I'm sorry that I hijacked your topic. Hopefully, it was fully answered. And I hope that everything goes well for you.

follansbee

Dr. West's point regarding frequency of scans is important and I agree with it. I was recently invited to a local practice to be a lung cancer expert for a dinner chat about controversies in lung cancer. It's a group that I've collaborated with on the care of many patients, and I've generally thought them to be very good doctors. I was surprised to learn that some of them were not getting scans after the 2 initial cycles of chemo (some were getting the 1st scan after 3 cycles, or one doc even after 4). Further, they told me that insurance typically won't pay for a scan after 2 cycles and this practice is therefor not unusual in community oncology. Similarly, I learned that I scan far more frequently than they do in the 2nd line setting as well.

At the time of progression, it's powerful to catch progression early. Ideally you want to catch progression when it's not yet causing suffering, switch drugs, and prevent said suffering. As Dr. West points out, one could look at the Fidias data on patients who became too sick to get 2nd line docetaxel as a lesson regarding the need for more frequent imaging. I would agree strongly. I am also not aware of any major data evaluating survival as a consequence of more intense or less intense monitoring for progression. While this would be a valuable study, even if it just forced insurance to pay for appropriate scans, I seriously doubt that it will ever get done, for practical reasons.

The value of ongoing therapy with the SAME drug is probably related to both the efficacy of the drug, and its side effect profile. It's not surprising that alimta, in PARAMOUNT was the first drug to properly show a benefit simply for prolonged duration therapy with the same drug. For nonsquamous patients it's a very effective drug. Further, it has the most favorable side effect profile of any cytotoxic drug in use for lung cancer; I might even be tempted to call it more tolerable for the average patient than tarceva or xalkori.

And thank you, Dr. Weiss. My oncologist sounds so mch like the oncologists that you visited. Maybe the insurance issue is the reason that my husband's doesn't want to order CT scans more often. We will ask him at our next visit. And we will take your comments and Dr West's with us and share them with him.