Does aggressive chemo lead to earlier death?

This research applies to people with metastatic non-small-cell lung cancer, but I found the results to be thought-provoking. Cancer itself has never made me feel sick, but chemo has often made me feel like I want to give up and die. Anyway, I know breast cancer and lung cancer are very different diseases. Any opinions?

http://www.nejm.org/doi/pdf/10.1056/NEJMoa1000678

Here's the abstract in case you can't open the link:

Background
Patients with metastatic non–small-cell lung cancer have a substantial symptom burden and may receive aggressive care at the end of life. We examined the effect of introducing palliative care early after diagnosis on patient-reported outcomes and end-of-life care among ambulatory patients with newly diagnosed disease.

Methods
We randomly assigned patients with newly diagnosed metastatic non–small-cell lung cancer to receive either early palliative care integrated with standard oncologic care or standard oncologic care alone. Quality of life and mood were assessed at baseline and at 12 weeks with the use of the Functional Assessment of Cancer Therapy–Lung (FACT-L) scale and the Hospital Anxiety and Depression Scale, respectively.

The primary outcome was the change in the quality of life at 12 weeks. Data on end-of-life care were collected from electronic medical records.

Results
Of the 151 patients who underwent randomization, 27 died by 12 weeks and 107 (86% of the remaining patients) completed assessments. Patients assigned to early palliative care had a better quality of life than did patients assigned to standard care (mean score on the FACT-L scale [in which scores range from 0 to 136, with higher scores indicating better quality of life], 98.0 vs. 91.5; P = 0.03). In addition, fewer patients in the palliative care group than in the standard care group had depressive symptoms (16% vs. 38%, P = 0.01). Despite the fact that fewer patients in the early palliative care group than in the standard care group received aggressive end-of-life care (33% vs. 54%, P = 0.05), median survival was longer among patients
receiving early palliative care (11.6 months vs. 8.9 months, P = 0.02).

Conclusions
Among patients with metastatic non–small-cell lung cancer, early palliative care led to significant improvements in both quality of life and mood. As compared with patients receiving standard care, patients receiving early palliative care had less
aggressive care at the end of life but longer survival.

(Funded by an American Society of Clinical Oncology Career Development Award and philanthropic gifts;
ClinicalTrials.gov number, NCT01038271.)

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I've read this study before and the only thing I could think of when I read it is how they don't talk about the cancer going away, only that quality of life was better just by making the symptoms more bareable. So, it leaves me wondering, are we doomed because our cancer is in the lungs? Is chemo pointless and we should just think about making the best of what time we have? I realize the chemo causes so many side effects and you feel miserable but this study really says on top of all that, it doesn't even work. I just hate that there isn't a better alternative for all of us...like a medical treatment that actually works!! Isn't that a novel idea.

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The official take on metastatic cancer is that it never really goes away, so I think that was one assumption in this study.

Remember that primary lung cancer is very different from breast cancer that has metastasized to the lungs. Also, from what I've heard, the people who get non-small cell lung cancer tend to be older than most breast cancer patients and sicker to start with -- and they often have a worse prognosis in general. I should have emphasized that more in more original post.

Still, the question is provocative, especially for those of us with TNBC and no other options for treatment than chemo. For example, I spent nearly a year on Abraxane/Avastin/Zometa only to hear my oncologist say when looking at scan results, "Well, I guess that this chemo didn't work." The scan results showed I had pretty much the lesions below the neck that I'd started out with the year before -- they hadn't shrunk and they hadn't grown, except a couple of bone lesions I'd had treated with radiation, and those had gone away.

Chemo doesn't get to the brain, and the disease in my brain progessed a bit over that year, but it didn't become deadly. So that tells me that since the chemo "didn't work," it's entirely possible that my body kept the cancer at a low ebb all by itself (with natorupathic treatments) for the whole time and the chemo did nothing but attempt to destroy my liver and kidneys.

There's some evidence that says that the taxanes (like Abraxane) drive cancer to the brain and that chemo can sometimes change the nature of slow-growing cancer, which I have, and make it agressive. So maybe another result of that year of treatment was to give me more brain lesions and potentially make the cancer worse everywhere else. I also went into a huge amount of debt, couldn't work, and there was no end of stress and strife for my family. And what was the point?

Does all of that make me angry. Well, yes it does. Quite angry.

So, when I look at this study that says that a certain population survives longer without aggressive treatment, I completely understand it from my own experience. I'd have been in the same health boat at the end of that year had I not had chemo, and I'd have been much better off mentally and financially. I realize that my experience isn't scientific evidence, but it's all I've got and I'm sticking to it! =)

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As I read the excerpt you posted, the lung cancer patients who are getting palliative care are getting it on top of the regular chemo. So I think they aren't getting less aggressive chemo.

But palliative care specialists are concerned about maximizing quality of life. It does make some sense that having as good quality of life as possible while on chemo could bring some survival benefits as well.

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I completely agree with you that it is so frustrating (to say the least) that you go through many months of a chemo that is causing havoc on your body and find out you have had no change. I just find it so discouraging that they don't know more and it's still such a crapshoot! I know I will risk ruining everything alternative I've done to try to build my body up to fight this disease the minute I start chemo and it could be all for nothing. In fact, I could be taking months off my life. But I guess, for that small chance that they will give me a chemo combo that works and sends me into NED, it's worth it.

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Good points, Nina.They didn't give up chemo entirely, but "patients receiving early palliative care had less
aggressive care at the end of life but longer survival." So, in those last few months or weeks, they definitely did back off on the aggressive chemo.

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There's a concept of chemotherapy being a zero sum game in certain situations which is very intriguing (e.g. metastatic breast cancer, platinum resistant ovarian cancer). You can push response rates higher with more intensive therapy, but you don't improve survival for the group as a whole. So every month of life you gain on one patient is a month lost in other patients.

The problem is that ineffective, aggressive chemotherapy can diminish not just the quality of life but also the quantity of life. Organ toxicity. Sepsis. Bleeding. Immunosuppression. Mutagenesis in genetically unstable tumor to more aggressive phenotypes. Perhaps mood lowering, with resultant changes in cytokines. So the real challenge is to kill tumor, while avoiding as much of the above as possible. It seems obvious, but that's not the paradigm being used.

The paradigm used is treatment to dose limiting effect. But the goal shouldn't necessarily be maximum tumor kill (in situations where it's just not possible to kill all of it). Tumor kill is probably a steep rise to steady plateau. But survival is probably like an inverted 'U' curve. You want to pick the right drugs and give them in such a way as to avoid the downslope of the inverted 'U.'

There appears to be a number of patients who have had long-term survival after high dose therapy, but there are a number of patients whose tumors are responsive to chemotherapy who have had long-term remissions from standard dose chemotherapy, as well as a number who show no difference in survival when treated with standard-dose or high-dose chemotherapy.

Does chemotherapy shorten survival of some patients, while prolonging the survival of others? You do help some patients, but for every patient helped, there's another one you may hurt.

You may want to reserve aggressive therapy for those patients who will derive more benefit than harm, while identifying the most promising treatment regimens for everyone. In patients with tumors very resistant to cytotoxic chemotherapy, the most promising treatments may be angiogenesis inhibitors, growth factor inhibitors, or more integrative medicine approaches.

More emphasis should be put on matching treatment to the patient (personalized medicine), through the use of individualized pre-testing, having more respect for minimal partial response or stable disease, when it can be achieved through use of the least toxic and mutagenic drug regimens, and reserve the use of higher dose therapy or aggressive combination chemotherapy to those patients with tumor biologies most amenable to attack and destroy by these aggressive treatments.

All cancer patients would certainly have a better chance of success had their cancer been "chemo-sensitive" rather than "chemo-resistant," where it is more apparent that chemotherapy improves the survival of patients, and where identifying the most effective chemotherapy would be more likely to improve survival.

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GP - Nicely said and very thought-provoking.

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JillAline

The less is more axiom often applies in cancer medicine. I'm not claiming that low dose therapy is to be preferred, anymore than claiming that high dose therapy is to be preferred. If one has a highly effective drug or drug regimen, then this should be given at the optimum dose to achieve whatever it is supposed to achieve.

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