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What level of side effects from systemic therapy are accepta


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What level of side effects from systemic therapy are acceptable? It depends on the goal of treatment.

May 3rd, 2013 - by Dr. Jack West

http://expertblog.lungevity.org/2013/05 ... -severity/

How much “toxicity”, the degree of side effects from treatment, should we accept when treating lung cancer? Of course, a huge amount of that answer depends on a particular person’s sense of what they are willing to accept, but another extremely important factor is the goal and setting of the treatment.

One of the most important, earliest questions we ask when treating cancer is what the realistic goals of treatment can be. Some patients have early stage cancer that can be treated with surgery and/or various other treatments to produce a reasonable chance of being cured. Other patients may have metastatic disease that is definitely treatable, with a realistic goal of prolonging survival and improving cancer-related symptoms, but we can’t honestly expect our treatments to cure the cancer. And even within the realm of non-curative therapy, some of our treatments are intended to be a limited course of a few cycles/months of treatment, while others may be intended to continue indefinitely, until a patient develops problematic side effects or evidence of significant progression of their disease.

A key point is that what is “acceptable” side effects is proportional to the potential benefit of treatment. If someone may need a very challenging treatment, such as a difficult surgery or time-limited course of chemo combined with radiation, but there’s a real probability that the therapy will be successful enough to cure the cancer, it’s generally worth trying to press ahead and work through everything that is tolerable over the short term. There’s a potentially big prize at the end, and rigorous treatment may be required to get it.

But we don’t have people go through heroic, dangerous surgeries or bone marrow transplants for the opportunity to prolong survival by a few weeks or a couple of months, because there is a very high probability that the treatment will be worse than the disease. In terms of advanced lung cancer, we want to ensure that treatments given are tolerable enough for people to be able to eat, ambulate, live their lives, and not suffer too much from what we’re doing to them. We need to pay much closer attention to the balance of benefit vs. risk when we can’t offer a reward of potential cure.

It has only been in the last 4-5 years that we have begun to routinely treat patients with maintenance therapy, which is a prolonged course of ongoing systemic (whole body, so intravenous or oral) therapy to provide prolonged suppressive effects against the cancer. We couldn’t realistically consider such an idea when our treatments were so challenging that people felt lucky to crawl to the finish after 3-4 months of treatment. But now we have some treatments like Alimta (pemetrexed) chemotherapy or Tarceva (erlotinib) oral targeted therapy that have demonstrated a modest but real benefit as maintenance therapy, which is only feasible because they are also often so well tolerated that people can continue on them for months and months in a row.

So for our treatments given with palliative intent (which really means “every treatment that isn’t going to be a cure”, and which is often life-prolonging, so palliative isn’t a euphemism for “comfort care with no expectation of survival benefit”), we want to ensure that we offer the best combination of efficacy against the cancer along with tolerability. If our treatment is intended to be for a fixed period of a few treatments followed by a break, it may be justifiable to push a person with a challenging treatment. On the other hand, I see some patients really suffering on maintenance therapy with chemo or Tarceva that they’re barely able to continue on, and which is actually limiting how well they can live while on treatment. That’s undermining one of the critical goals of our treatment, and it should make us step back and consider a break from treatment or cutting back on the dose in order to achieve a better balance of efficacy and tolerability.

I hope this idea of treatment being a balance of anti-cancer activity and quality of life makes sense, and that the optimal balance should depend on what that treatment might deliver. I welcome any questions or comments you might have.

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