In contrast to the guidelines that exist for treating advanced lung cancer in the first-line setting for 4-6 cycles, there are really just practice patterns and good judgment to guide decisions of how long to treat in the second-line therapy.  First, this is a relatively new question.  As I previously mentioned when describing the history of treatment for advanced lung cancer, ten years ago there was plenty of debate about whether the benefits of treating NSCLC were sufficient to make this a standard of care.  Second-line chemo for NSCLC with taxotere was first approved by the US FDA in 2000, and topotecan in 1998 for previously treated (and sensitive disease) ED-SCLC.   So these are new issues. 

  The general issue of whether to continue second-line treatment in patients with prolonged non-progression is “we should be so lucky” – we wish we had many more patients who are doing well on second-line therapy for so long that we could ask questions of whether to take breaks on treatment or not.   In the large randomized trial that directly compared taxotere to alimta in the second-line NSCLC setting (abstract here), both groups had a median number of 4 cycles administered.  The median duration of a response was about 5 months for both groups, and some responses went out much further (up to about 12 months on taxotere, 15 months on alimta).  Without any clear guidelines, and with not enough patients fortunate enough to still be showing response or stable disease many months into treatment, we will often continue therapy until progression.  The more tolerable the treatment, the easier it is to have treatment continue for many months in the setting of ongoing stable disease.  But there haven’t been enough patients available to study the question of whether there is a benefit of continuing indefinitely without a break.  Patients often want to keep going, and oncologists are also pleased to have them doing well, so the default choice is to keep going unless there is a reason to stop.  The even more limited number of studies of relapsed SCLC have had a similar approach of treating on an ongoing basis in the absence of progression or prohibitive toxicity, and there is a small subset of patients who continued on treatment for more than a year (for instance, in the trial showing improved quality of life with topotecan, abstract here).

   This is a more common issue with EGFR inhibitors like iressa and tarceva, both because they can often be very well tolerated and amenable to chronic use, and also because there is a subset of patients who have a very prolonged response or stable disease on them.  In the BR.21 trial (abstract here), the median duration of response on tarceva was about 8 months.  And there are a significant minority of patients who have shown no evidence of progression on one of these agents for more than one or two years or more.  In such cases, the idea of stopping effective therapy has rarely been considered, by physicians or patients.  I sometimes wonder whether we could prolong the period of sensitivity to tarceva in the long-term responders by treating “intermittently”, holding it for a few months and restarting at clear progression, in order to minimize the ability of a cancer to develop resistance, but I don’t think the world is ready to pursue that concept yet.

   Overall, I do approach second-line and later therapies differently than first-line, for both NSCLC and SCLC, and am happy to have patients continue on a therapy as long as they are not demonstrating progression and are able to tolerate prolonged therapy.  We would all like to develop so many effective and long-lasting therapies that we need to develop strategies for chronic management.  One step at a time, I suppose.